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Cancer and Metastasis Reviews
Published in: Cancer and Metastasis Reviews 1/2024

03-01-2024 | Metastasis | REVIEW

Targeting the key players of phenotypic plasticity in cancer cells by phytochemicals

Authors: Sajad Fakhri, Seyed Zachariah Moradi, Fatemeh Abbaszadeh, Farahnaz Faraji, Roshanak Amirian, Dona Sinha, Emily G. McMahon, Anupam Bishayee

Published in: Cancer and Metastasis Reviews | Issue 1/2024

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Abstract

Plasticity of phenotypic traits refers to an organism’s ability to change in response to environmental stimuli. As a result, the response may alter an organism’s physiological state, morphology, behavior, and phenotype. Phenotypic plasticity in cancer cells describes the considerable ability of cancer cells to transform phenotypes through non-genetic molecular signaling activities that promote therapy evasion and tumor metastasis via amplifying cancer heterogeneity. As a result of metastable phenotypic state transitions, cancer cells can tolerate chemotherapy or develop transient adaptive resistance. Therefore, new findings have paved the road in identifying factors and agents that inhibit or suppress phenotypic plasticity. It has also investigated novel multitargeted agents that may promise new effective strategies in cancer treatment. Despite the efficiency of conventional chemotherapeutic agents, drug toxicity, development of resistance, and high-cost limit their use in cancer therapy. Recent research has shown that small molecules derived from natural sources are capable of suppressing cancer by focusing on the plasticity of phenotypic responses. This systematic, comprehensive, and critical review analyzes the current state of knowledge regarding the ability of phytocompounds to target phenotypic plasticity at both preclinical and clinical levels. Current challenges/pitfalls, limitations, and future perspectives are also discussed.
Literature
1.
Stewart, B. W., Bray, F., Forman, D., Ohgaki, H., Straif, K., Ullrich, A., et al. (2016). Cancer prevention as part of precision medicine: 'Plenty to be done' Carcinogenesis, 37(1), 2–9.PubMed
2.
Hanahan, D. (2022). Hallmarks of cancer: New dimensions. Cancer Discovery, 12(1), 31–46.PubMed
3.
Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: The next generation. Cell, 144(5), 646–674.PubMed
4.
Kalluri, R., & Weinberg, R. A. (2009). The basics of epithelial-mesenchymal transition. The Journal of Clinical Investigation, 119(6), 1420–1428.PubMedPubMedCentral
5.
Ribatti, D., Tamma, R., & Annese, T. (2020). Epithelial-mesenchymal transition in cancer: A historical overview. Translational Oncology, 13(6), 100773.PubMedPubMedCentral
6.
Cadoná, F. C., Dantas, R. F., de Mello, G. H., & Silva-Jr, F. P. (2022). Natural products targeting into cancer hallmarks: An update on caffeine, theobromine, and (+)-catechin. Critical Reviews in Food Science and Nutrition, 62(26), 7222–7241.PubMed
7.
8.
Huang, M., Lu, J.-J., & Ding, J. (2021). Natural products in cancer therapy: Past, present and future. Natural Products and Bioprospecting, 11(1), 5–13.PubMedPubMedCentral
9.
10.
11.
Ang, H. L., Mohan, C. D., Shanmugam, M. K., Leong, H. C., Makvandi, P., Rangappa, K. S., et al. (2023). Mechanism of epithelial-mesenchymal transition in cancer and its regulation by natural compounds. Medicinal Research Reviews, 43(4), 1141–1200.PubMed
12.
Das, B., Sarkar, N., Bishayee, A., & Sinha, D. (2019). Dietary phytochemicals in the regulation of epithelial to mesenchymal transition and associated enzymes: A promising anticancer therapeutic approach. In Semin Cancer Biol (Vol. 56, pp. 196–218): Elsevier
13.
Avila-Carrasco, L., Majano, P., Sánchez-Toméro, J. A., Selgas, R., López-Cabrera, M., Aguilera, A., et al. (2019). Natural plants compounds as modulators of epithelial-to-mesenchymal transition. Frontiers in Pharmacology, 10, 715.PubMedPubMedCentral
14.
More, H. The immortality of the soul, so farre as it is demonstrable from the knowledge of nature and the light of reason. Eebo Editions, Proquest.
15.
16.
Darwin, C. (2004). On the origin of species, 1859. Routledge.
17.
Baldwin, J, M. (1896). Physical and social heredity. American Naturalist, 422–428.
18.
Woltereck, R. (1909). Weitere experimentelle Untersuchungen uber Artveranderung, speziell uberdas Wesen quantitativer Artunterschyiede bei Daphniden. Verhandlungen der Deutschen Zoologischen Gesellschaft, 1909, 110–172.
19.
Poulton, E. B. (1892). XIX. Further experiments upon the colour‐relation between certain lepidopterous larvœ, pupœ, cocoons, and imagines and their surroundings. Transactions of the Royal Entomological Society of London, 40(4), 293–487.
20.
21.
Johannsen, W. (1911). The genotype conception of heredity. The American Naturalist, 45(531), 129–159.
22.
Schmalhausen, I. I. (1949). Factors of evolution: The theory of stabilizing selection. Blakiston.
23.
Waddington, C. H. (1975). The evolution of an evolutionist. Edinburgh: Edinburgh University Press.
24.
Mayr, E. (1963). Animal species and evolution. Cambridge, MA: Harvard University Press.
25.
Bradshaw, A. D. (1965). Evolutionary significance of phenotypic plasticity in plants. Advances in Genetics, 13, 115–155.
26.
Gilbert, S. F. (2005). Mechanisms for the environmental regulation of gene expression: Ecological aspects of animal development. Journal of Biosciences, 30, 65–74.PubMed
27.
Clark, M. S. (2020). Molecular mechanisms of biomineralization in marine invertebrates. Journal of Experimental Biology, 223(11), jeb206961.PubMedPubMedCentral
28.
Kucharski, R., Maleszka, J., Foret, S., & Maleszka, R. (2008). Nutritional control of reproductive status in honeybees via DNA methylation. Science, 319(5871), 1827–1830.PubMed
29.
Gupta, P. B., Pastushenko, I., Skibinski, A., Blanpain, C., & Kuperwasser, C. (2019). Phenotypic plasticity: Driver of cancer initiation, progression, and therapy resistance. Cell Stem Cell, 24(1), 65–78.PubMed
30.
Pastushenko, I., & Blanpain, C. (2019). EMT transition states during tumor progression and metastasis. Trends in Cell Biology, 29(3), 212–226.PubMed
31.
Javaid, S., Zhang, J., Anderssen, E., Black, J. C., Wittner, B. S., Tajima, K., et al. (2013). Dynamic chromatin modification sustains epithelial-mesenchymal transition following inducible expression of Snail-1. Cell Reports, 5(6), 1679–1689.PubMed
32.
Marcucci, F., Stassi, G., & De Maria, R. (2016). Epithelial–mesenchymal transition: A new target in anticancer drug discovery. Nature Reviews Drug Discovery, 15(5), 311–325.PubMed
33.
Ungefroren, H., Thürling, I., Färber, B., Kowalke, T., Fischer, T., De Assis, L. V. M., et al. (2022). The quasimesenchymal pancreatic ductal epithelial cell line PANC-1-A useful model to study clonal heterogeneity and EMT subtype shifting. Cancers (Basel), 14(9), https://​doi.​org/​10.​3390/​cancers14092057
34.
Dongre, A., & Weinberg, R. A. (2019). New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer. Nature Reviews Molecular Cell Biology, 20(2), 69–84.PubMed
35.
36.
Muz, B., de la Puente, P., Azab, F., & Azab, A. K. (2015). The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia, 3, 83.PubMedPubMedCentral
37.
Michealraj, K. A., Kumar, S. A., Kim, L. J., Cavalli, F. M., Przelicki, D., Wojcik, J. B., et al. (2020). Metabolic regulation of the epigenome drives lethal infantile ependymoma. Cell, 181(6), 1329–1345. e1324
38.
Li, L., & Hanahan, D. (2013). Hijacking the neuronal NMDAR signaling circuit to promote tumor growth and invasion. Cell, 153(1), 86–100.PubMed
39.
Mohammadi, H., & Sahai, E. (2018). Mechanisms and impact of altered tumour mechanics. Nature Cell Biology, 20(7), 766–774.PubMed
40.
Visvader, J. E. (2011). Cells of origin in cancer. Nature, 469(7330), 314–322.PubMed
41.
Rycaj, K., & Tang, D. G. (2015). Cell-of-origin of cancer versus cancer stem cells: Assays and interpretations. Cancer Research, 75(19), 4003–4011.PubMedPubMedCentral
42.
Ince, T. A., Richardson, A. L., Bell, G. W., Saitoh, M., Godar, S., Karnoub, A. E., et al. (2007). Transformation of different human breast epithelial cell types leads to distinct tumor phenotypes. Cancer Cell, 12(2), 160–170.PubMed
43.
44.
Suraneni, M. V., & Badeaux, M. D. (2013). Tumor-initiating cells, cancer metastasis and therapeutic implications. In Madame Curie Bioscience Database [Internet]: Landes Bioscience.
45.
Cermeño, E. A., & García, A. J. (2016). Tumor-initiating cells: Emerging biophysical methods of isolation. Current stem cell reports, 2, 21–32.PubMedPubMedCentral
46.
47.
48.
49.
van de Stolpe, A. (2013). On the origin and destination of cancer stem cells: A conceptual evaluation. American Journal of Cancer Research, 3(1), 107–116.PubMedPubMedCentral
50.
51.
Osman, A., Afify, S. M., Hassan, G., Fu, X., Seno, A., & Seno, M. (2020). Revisiting cancer stem cells as the origin of cancer-associated cells in the tumor microenvironment: A hypothetical view from the potential of iPSCs. Cancers, 12(4), 879.PubMedPubMedCentral
52.
Zhu, L., Gibson, P., Currle, D. S., Tong, Y., Richardson, R. J., Bayazitov, I. T., et al. (2009). Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature, 457(7229), 603–607.PubMed
53.
Barker, N., Ridgway, R. A., Van Es, J. H., Van De Wetering, M., Begthel, H., Van Den Born, M., et al. (2009). Crypt stem cells as the cells-of-origin of intestinal cancer. Nature, 457(7229), 608–611.PubMed
54.
Kim, C. F. B., Jackson, E. L., Woolfenden, A. E., Lawrence, S., Babar, I., Vogel, S., et al. (2005). Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell, 121(6), 823–835.PubMed
55.
Bouras, T., Pal, B., Vaillant, F., Harburg, G., Asselin-Labat, M.-L., Oakes, S. R., et al. (2008). Notch signaling regulates mammary stem cell function and luminal cell-fate commitment. Cell Stem Cell, 3(4), 429–441.PubMed
56.
Wang, X., Julio, M.K.-D., Economides, K. D., Walker, D., Yu, H., Halili, M. V., et al. (2009). A luminal epithelial stem cell that is a cell of origin for prostate cancer. Nature, 461(7263), 495–500.PubMedPubMedCentral
57.
Lawson, D. A., Zong, Y., Memarzadeh, S., Xin, L., Huang, J., & Witte, O. N. (2010). Basal epithelial stem cells are efficient targets for prostate cancer initiation. Proceedings of the National Academy of Sciences, 107(6), 2610-2615.
58.
Korsten, H., Ziel-van der Made, A., Ma, X., van der Kwast, T., & Trapman, J. (2009). Accumulating progenitor cells in the luminal epithelial cell layer are candidate tumor initiating cells in a Pten knockout mouse prostate cancer model. PLoS One, 4(5), e5662.PubMedPubMedCentral
59.
Friedlander, S. Y. G., Chu, G. C., Snyder, E. L., Girnius, N., Dibelius, G., Crowley, D., et al. (2009). Context-dependent transformation of adult pancreatic cells by oncogenic K-Ras. Cancer Cell, 16(5), 379–389.
60.
Barker, N., Huch, M., Kujala, P., van de Wetering, M., Snippert, H. J., van Es, J. H., et al. (2010). Lgr5+ ve stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell, 6(1), 25–36.PubMed
61.
Holland, E. C., Celestino, J., Dai, C., Schaefer, L., Sawaya, R. E., & Fuller, G. N. (2000). Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice. Nature Genetics, 25(1), 55–57.PubMed
62.
Bachoo, R. M., Maher, E. A., Ligon, K. L., Sharpless, N. E., Chan, S. S., You, M. J., et al. (2002). Epidermal growth factor receptor and Ink4a/Arf: Convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis. Cancer Cell, 1(3), 269–277.PubMed
63.
Jacques, T. S., Swales, A., Brzozowski, M. J., Henriquez, N. V., Linehan, J. M., Mirzadeh, Z., et al. (2010). Combinations of genetic mutations in the adult neural stem cell compartment determine brain tumour phenotypes. The EMBO Journal, 29(1), 222–235.PubMed
64.
Lindberg, N., Kastemar, M., Olofsson, T., Smits, A., & Uhrbom, L. (2009). Oligodendrocyte progenitor cells can act as cell of origin for experimental glioma. Oncogene, 28(23), 2266–2275.PubMed
65.
Gibson, P., Tong, Y., Robinson, G., Thompson, M. C., Currle, D. S., Eden, C., et al. (2010). Subtypes of medulloblastoma have distinct developmental origins. Nature, 468(7327), 1095–1099.PubMedPubMedCentral
66.
Johnson, R. A., Wright, K. D., Poppleton, H., Mohankumar, K. M., Finkelstein, D., Pounds, S. B., et al. (2010). Cross-species genomics matches driver mutations and cell compartments to model ependymoma. Nature, 466(7306), 632–636.PubMedPubMedCentral
67.
Thiery, J. P., Acloque, H., Huang, R. Y., & Nieto, M. A. (2009). Epithelial-mesenchymal transitions in development and disease. Cell, 139(5), 871–890.PubMed
68.
Bhatia, S., Wang, P., Toh, A., & Thompson, E. W. (2020). New insights into the role of phenotypic plasticity and EMT in driving cancer progression. Frontiers in Molecular Biosciences, 7, 71.PubMedPubMedCentral
69.
Lambert, A. W., Pattabiraman, D. R., & Weinberg, R. A. (2017). Emerging biological principles of metastasis. Cell, 168(4), 670–691.PubMedPubMedCentral
70.
Jehanno, C., Vulin, M., Richina, V., Richina, F., & Bentires-Alj, M. (2022). Phenotypic plasticity during metastatic colonization. Trends in Cell Biology.
71.
Ocaña, O. H., Corcoles, R., Fabra, A., Moreno-Bueno, G., Acloque, H., Vega, S., et al. (2012). Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell, 22(6), 709–724.PubMed
72.
Mani, S. A., Guo, W., Liao, M.-J., Eaton, E. N., Ayyanan, A., Zhou, A. Y., et al. (2008). The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell, 133(4), 704–715.PubMedPubMedCentral
73.
Del Vecchio, C. A., Feng, Y., Sokol, E. S., Tillman, E. J., Sanduja, S., Reinhardt, F., et al. (2014). De-differentiation confers multidrug resistance via noncanonical PERK-Nrf2 signaling. PLoS Biology, 12(9), e1001945.PubMedPubMedCentral
74.
Feng, Y.-X., Jin, D. X., Sokol, E. S., Reinhardt, F., Miller, D. H., & Gupta, P. B. (2017). Cancer-specific PERK signaling drives invasion and metastasis through CREB3L1. Nature Communications, 8(1), 1079.PubMedPubMedCentral
75.
Goldman, A. (2016). Tailoring combinatorial cancer therapies to target the origins of adaptive resistance. Molecular & cellular oncology, 3(1), e1030534.
76.
Qin, S., Jiang, J., Lu, Y., Nice, E. C., Huang, C., Zhang, J., et al. (2020). Emerging role of tumor cell plasticity in modifying therapeutic response. Signal Transduction and Targeted Therapy, 5(1), 228.PubMedPubMedCentral
77.
Shibue, T., & Weinberg, R. A. (2017). EMT, CSCs, and drug resistance: The mechanistic link and clinical implications. Nature Reviews Clinical Oncology, 14(10), 611–629.PubMedPubMedCentral
78.
Lüönd, F., Sugiyama, N., Bill, R., Bornes, L., Hager, C., Tang, F., et al. (2021). Distinct contributions of partial and full EMT to breast cancer malignancy. Developmental Cell, 56(23), 3203–3221. e3211
79.
Bakir, B., Chiarella, A. M., Pitarresi, J. R., & Rustgi, A. K. (2020). EMT, MET, plasticity, and tumor metastasis. Trends in Cell Biology, 30(10), 764–776.PubMedPubMedCentral
80.
Pastushenko, I., Brisebarre, A., Sifrim, A., Fioramonti, M., Revenco, T., Boumahdi, S., et al. (2018). Identification of the tumour transition states occurring during EMT. Nature, 556(7702), 463–468.PubMed
81.
Shi, Z.-D., Pang, K., Wu, Z.-X., Dong, Y., Hao, L., Qin, J.-X., et al. (2023). Tumor cell plasticity in targeted therapy-induced resistance: Mechanisms and new strategies. Signal Transduction and Targeted Therapy, 8(1), 113.PubMedPubMedCentral
82.
Merrell, A. J., & Stanger, B. Z. (2016). Adult cell plasticity in vivo: De-differentiation and transdifferentiation are back in style. Nature Reviews Molecular Cell Biology, 17(7), 413–425.PubMedPubMedCentral
83.
Das, M., & Law, S. (2018). Role of tumor microenvironment in cancer stem cell chemoresistance and recurrence. The International Journal of Biochemistry & Cell Biology, 103, 115–124.
84.
Yochum, Z. A., Cades, J., Wang, H., Chatterjee, S., Simons, B. W., O’Brien, J. P., et al. (2019). Targeting the EMT transcription factor TWIST1 overcomes resistance to EGFR inhibitors in EGFR-mutant non-small-cell lung cancer. Oncogene, 38(5), 656–670.PubMed
85.
Dai, C., Heemers, H., & Sharifi, N. (2017). Androgen signaling in prostate cancer. Cold Spring Harbor Perspectives in Medicine, 7(9), a030452.PubMedPubMedCentral
86.
Lee, H., Jeong, A. J., & Ye, S.-K. (2019). Highlighted STAT3 as a potential drug target for cancer therapy. BMB Reports, 52(7), 415.PubMedPubMedCentral
87.
East, M. P., & Johnson, G. L. (2022). Adaptive chromatin remodeling and transcriptional changes of the functional kinome in tumor cells in response to targeted kinase inhibition. Journal of Biological Chemistry, 298(2), 101525.PubMed
88.
Salaritabar, A., Berindan-Neagoe, I., Darvish, B., Hadjiakhoondi, F., Manayi, A., Devi, K. P., et al. (2019). Targeting Hedgehog signaling pathway: Paving the road for cancer therapy. Pharmacological Research, 141, 466–480.PubMed
89.
90.
Tan, T., Shi, P., Abbas, M. N., Wang, Y., Xu, J., Chen, Y., et al. (2022). Epigenetic modification regulates tumor progression and metastasis through EMT. International Journal of Oncology, 60(6), 1–17.
91.
Knoechel, B., Roderick, J. E., Williamson, K. E., Zhu, J., Lohr, J. G., Cotton, M. J., et al. (2014). An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia. Nature Genetics, 46(4), 364–370.PubMedPubMedCentral
92.
Guo, L., Lee, Y.-T., Zhou, Y., & Huang, Y. (2022). Targeting epigenetic regulatory machinery to overcome cancer therapy resistance. In Seminars in Cancer Biology, (Vol. 83, pp. 487–502): Elsevier
93.
Yosifov, D. Y., Bloehdorn, J., Döhner, H., Lichter, P., Stilgenbauer, S., & Mertens, D. (2020). DNA methylation of chronic lymphocytic leukemia with differential response to chemotherapy. Scientific Data, 7(1), 133.PubMedPubMedCentral
94.
Barzegar Behrooz, A., Talaie, Z., Jusheghani, F., Łos, M. J., Klonisch, T., & Ghavami, S. (2022). Wnt and PI3K/Akt/mTOR survival pathways as therapeutic targets in glioblastoma. International Journal of Molecular Sciences, 23(3), 1353.PubMedPubMedCentral
95.
96.
Howe, L. R., Watanabe, O., Leonard, J., & Brown, A. M. (2003). Twist is up-regulated in response to Wnt1 and inhibits mouse mammary cell differentiation. Cancer Research, 63(8), 1906–1913.PubMed
97.
Saad, S., Stanners, S., Yong, R., Tang, O., & Pollock, C. (2010). Notch mediated epithelial to mesenchymal transformation is associated with increased expression of the Snail transcription factor. The International Journal of Biochemistry & Cell Biology, 42(7), 1115–1122.
98.
Deshmukh, A. P., Vasaikar, S. V., Tomczak, K., Tripathi, S., Den Hollander, P., Arslan, E., et al. (2021). Identification of EMT signaling cross-talk and gene regulatory networks by single-cell RNA sequencing. Proceedings of the National Academy of Sciences, 118(19), e2102050118.
99.
von Arx, C., Capozzi, M., López-Jiménez, E., Ottaiano, A., Tatangelo, F., Di Mauro, A., et al. (2019). Updates on the role of molecular alterations and NOTCH signalling in the development of neuroendocrine neoplasms. Journal of Clinical Medicine, 8(9), 1277.
100.
Noman, M. Z., Hasmim, M., Lequeux, A., Xiao, M., Duhem, C., Chouaib, S., et al. (2019). Improving cancer immunotherapy by targeting the hypoxic tumor microenvironment: New opportunities and challenges. Cells, 8(9), 1083.PubMedPubMedCentral
101.
Zheng, X., Yu, C., & Xu, M. (2021). Linking tumor microenvironment to plasticity of cancer stem cells: Mechanisms and application in cancer therapy. Frontiers in Oncology, 11, 678333.PubMedPubMedCentral
102.
Kalluri, R., & Zeisberg, M. (2006). Fibroblasts in cancer. Nature Reviews Cancer, 6(5), 392–401.PubMed
103.
104.
Xu, W., Yang, Z., & Lu, N. (2015). A new role for the PI3K/Akt signaling pathway in the epithelial-mesenchymal transition. Cell Adhesion & Migration, 9(4), 317–324.
105.
Lee, M. K., Pardoux, C., Hall, M. C., Lee, P. S., Warburton, D., Qing, J., et al. (2007). TGF-β activates Erk MAP kinase signalling through direct phosphorylation of ShcA. The EMBO Journal, 26(17), 3957–3967.PubMedPubMedCentral
106.
Zhang, J., & Ma, L. (2012). MicroRNA control of epithelial–mesenchymal transition and metastasis. Cancer and Metastasis Reviews, 31, 653–662.PubMed
107.
108.
109.
110.
111.
112.
113.
114.
115.
116.
117.
118.
119.
120.
121.
122.
123.
124.
125.
126.
127.
128.
129.
130.
Yu, G., Chen, L., Hu, Y., Yuan, Z., Luo, Y., & Xiong, Y. (2021). Antitumor effects of baicalein and its mechanism via TGF<i>β</i> pathway in cervical cancer HeLa Cells. Evidence-based Complementary and Alternative Medicine, 2021, https://​doi.​org/​10.​1155/​2021/​5527190
131.
132.
Xing-Cong, M., Yan, W., Zhi-Jun, D., Gao, X., Ma, Y., Xu, Q., et al. (2016). Baicalein suppresses metastasis of breast cancer cells by inhibiting EMT via downregulation of SATB1 and Wnt/β-catenin pathway. Drug Design, Development and Therapy, 10, 1419–1441. https://​doi.​org/​10.​2147/​DDDT.​S102541CrossRef
133.
Zheng, L., Zhou, Z. Y., & He, Z. K. (2016). Baicalin inhibits TGF-beta 1-induced epithelial-to-mesenchymal transition and suppresses pancreatic cancer cell migration and invasion. International Journal of Clinical and Experimental Pathology, 9(2), 1054–1060.
134.
135.
Weichao, D., Fan, Y., Hou, T., Wei, Y., Liu, B., Que, T., et al. (2022). Silibinin inhibits the migration, invasion and epithelial-mesenchymal transition of prostate cancer by activating the autophagic degradation of YAP. Journal of Cancer, 13(13), 3415–3426. https://​doi.​org/​10.​7150/​jca.​63514CrossRef
136.
137.
Chen, J. W., & Qiu, H. (2021). Analysis of inhibitory effects of kaempferol on migration and epithelial-mesenchymal transition in human lung cancer. Latin American Journal of Pharmacy, 40(1), 108–113.
138.
139.
Zhang, Z., Qiao, Y., Yang, L., Chen, Z., Li, T., Gu, M., et al. (2021). Kaempferol 3-O-gentiobioside, an ALK5 inhibitor, affects the proliferation, migration, and invasion of tumor cells via blockade of the TGF-β/ALK5/Smad signaling pathway. Phytotherapy Research, 35(11), 6310–6323. https://​doi.​org/​10.​1002/​ptr.​7278CrossRefPubMed
140.
Wei, R., Penso, N. E. C., Hackman, R. M., Wang, Y., & Mackenzie, G. G. (2019). Epigallocatechin-3-gallate (EGCG) suppresses pancreatic cancer cell growth, invasion, and migration partly through the inhibition of Akt pathway and epithelial-mesenchymal transition: Enhanced efficacy when combined with gemcitabine. Nutrients, 11(8), https://​doi.​org/​10.​3390/​nu11081856
141.
Shi, J., Liu, F., Zhang, W., Liu, X., Lin, B., & Tang, X. (2015). Epigallocatechin-3-gallate inhibits nicotine-induced migration and invasion by the suppression of angiogenesis and epithelial-mesenchymal transition in non-small cell lung cancer cells. Oncology Reports, 33(6), 2972–2980. https://​doi.​org/​10.​3892/​or.​2015.​3889CrossRefPubMed
142.
143.
144.
145.
146.
147.
148.
149.
150.
151.
Prasad, P., Vasas, A., Hohmann, J., Bishayee, A., & Sinha, D. (2019). Cirsiliol suppressed epithelial to mesenchymal transition in B16F10 malignant melanoma cells through alteration of the PI3K/Akt/NF-κB signaling pathway. International Journal of Molecular Sciences, 20(3), https://​doi.​org/​10.​3390/​ijms20030608.
152.
153.
154.
155.
156.
157.
158.
159.
160.
161.
Singh, T., Prasad, R., & Katiyar, S. K. (2016). Therapeutic intervention of silymarin on the migration of non-small cell lung cancer cells is associated with the axis of multiple molecular targets including class 1 HDACs, ZEB1 expression, and restoration of miR-203 and E-cadherin expression. American Journal of Cancer Research, 6(6), 1287–1301.PubMedPubMedCentral
162.
163.
Jia, H., Liu, M. Y., Wang, X. Y., Jiang, Q. Y., Wang, S., Santhanam, R. K., et al. (2021). Cimigenoside functions as a novel gamma-secretase inhibitor and inhibits the proliferation or metastasis of human breast cancer cells by gamma-secretase/Notch axis. Pharmacological Research, 169, https://​doi.​org/​10.​1016/​j.​phrs.​2021.​105686
164.
165.
Lee, J., Jin, H., Lee, W. S., Nagappan, A., Choi, Y. H., Kim, G. S., et al. (2016). Morin, a flavonoid from moraceae, inhibits cancer cell adhesion to endothelial cells and EMT by downregulating VCAM1 and Ncadherin. Asian Pacific Journal of Cancer Prevention, 17(7), 3071–3075.PubMed
166.
167.
168.
169.
170.
171.
172.
173.
174.
175.
176.
177.
178.
179.
Lu, K. H., Chen, P. N., Hsieh, Y. H., Lin, C. Y., Cheng, F. Y., Chiu, P. C., et al. (2016). 3-Hydroxyflavone inhibits human osteosarcoma U2OS and 143B cells metastasis by affecting EMT and repressing u-PA/MMP-2 via FAK-Src to MEK/ERK and RhoA/MLC2 pathways and reduces 143B tumor growth in vivo. Food and Chemical Toxicology, 97, 177–186. https://​doi.​org/​10.​1016/​j.​fct.​2016.​09.​006CrossRefPubMed
180.
181.
182.
Chen, H. Y., Chiang, Y. F., Huang, J. S., Huang, T. C., Shih, Y. H., Wang, K. L., et al. (2021). Isoliquiritigenin reverses epithelial-mesenchymal transition through modulation of the TGF-β/Smad signaling pathway in endometrial cancer. Cancers (Basel), 13(6). https://​doi.​org/​10.​3390/​cancers13061236
183.
Chen, S. M., Feng, J. N., Zhao, C. K., Yao, L. C., Wang, L. X., Meng, L., et al. (2022). A multi-targeting natural product, aiphanol, inhibits tumor growth and metastasis. American Journal of Cancer Research, 12(11), 4930–4953.PubMedPubMedCentral
184.
185.
López-Lázaro, M. (2009). Distribution and biological activities of the flavonoid luteolin. Mini Reviews in Medicinal Chemistry, 9(1), 31–59.PubMed
186.
187.
188.
189.
190.
Khan, F., Niaz, K., Maqbool, F., Ismail Hassan, F., Abdollahi, M., Nagulapalli Venkata, K. C., et al. (2016). Molecular targets underlying the anticancer effects of quercetin: An update. Nutrients, 8(9), https://​doi.​org/​10.​3390/​nu8090529.
191.
192.
193.
194.
Morshed, A., Paul, S., Hossain, A., Basak, T., Hossain, M. S., Hasan, M. M., et al. (2023). Baicalein as promising anticancer agent: A comprehensive analysis on molecular mechanisms and therapeutic perspectives. Cancers (Basel), 15(7), https://​doi.​org/​10.​3390/​cancers15072128
195.
196.
197.
198.
199.
Fakhri, S., Abdian, S., Zarneshan, S. N., Moradi, S. Z., Farzaei, M. H., & Abdollahi, M. (2022). Nanoparticles in combating neuronal dysregulated signaling pathways: Recent approaches to the nanoformulations of phytochemicals and synthetic drugs against neurodegenerative diseases. International Journal of Nanomedicine, 299–331. https://​doi.​org/​10.​2147/​IJN.​S347187
200.
Moradi, S. Z., Momtaz, S., Bayrami, Z., Farzaei, M. H., & Abdollahi, M. (2020). Nanoformulations of herbal extracts in treatment of neurodegenerative disorders. Frontiers in Bioengineering and Biotechnology, 8, 238.PubMedPubMedCentral
201.
Sajadimajd, S., Moradi, S. Z., Akbari, V., Aghaz, F., & Farzaei, M. H. (2022). Nanoformulated herbal bioactives for the treatment of neurodegenerative disorders. In Herbal bioactive-based drug delivery systems (pp. 371–391): Elsevier.
202.
203.
204.
205.
Kubina, R., Krzykawski, K., Kabała-Dzik, A., Wojtyczka, R. D., Chodurek, E., & Dziedzic, A. (2022). Fisetin, a potent anticancer flavonol exhibiting cytotoxic activity against neoplastic malignant cells and cancerous conditions: A scoping, comprehensive review. Nutrients, 14(13), https://​doi.​org/​10.​3390/​nu14132604
206.
207.
208.
209.
210.
Liu, C. H., Tang, W. C., Sia, P., Huang, C. C., Yang, P. M., Wu, M. H., et al. (2015). Berberine inhibits the metastatic ability of prostate cancer cells by suppressing epithelial-to-mesenchymal transition (EMT)-associated genes with predictive and prognostic relevance. International Journal of Medical Sciences, 12(1), 63–71. https://​doi.​org/​10.​7150/​ijms.​9982CrossRefPubMedPubMedCentral
211.
212.
213.
214.
Liu, T., Li, K., Zhang, Z., Peng, J., Yang, J., Law, B. Y. K., et al. (2023). Tetrandrine inhibits cancer stem cell characteristics and epithelial to mesenchymal transition in triple-negative breast cancer via SOD1/ROS signaling pathway. The American Journal of Chinese Medicine, 1–20. https://​doi.​org/​10.​1142/​s0192415x2350022​2
215.
Zhang, Z., Liu, T., Yu, M., Li, K., & Li, W. (2018). The plant alkaloid tetrandrine inhibits metastasis via autophagy-dependent Wnt/β-catenin and metastatic tumor antigen 1 signaling in human liver cancer cells. Journal of Experimental & Clinical Cancer Research, 37(1), 7. https://​doi.​org/​10.​1186/​s13046-018-0678-6CrossRef
216.
Zhao, B., Hui, X., Wang, J., Zeng, H., Yan, Y., Hu, Q., et al. (2021). Matrine suppresses lung cancer metastasis via targeting M2-like tumour-associated-macrophages polarization. American Journal of Cancer Research, 11(9), 4308–4328.PubMedPubMedCentral
217.
218.
219.
220.
He, J., Chen, S., Yu, T., Chen, W., Huang, J., Peng, C., et al. (2022). Harmine suppresses breast cancer cell migration and invasion by regulating TAZ-mediated epithelial-mesenchymal transition. American Journal of Cancer Research, 12(6), 2612–2626.PubMedPubMedCentral
221.
Shi, S., Li, C., Zhang, Y., Deng, C., Tan, M., Pan, G., et al. (2021). Lycorine hydrochloride inhibits melanoma cell proliferation, migration and invasion via down-regulating p21(Cip1/WAF1). American Journal of Cancer Research, 11(4), 1391–1409.PubMedPubMedCentral
222.
Yuan, X. H., Zhang, P., Yu, T. T., Huang, H. K., Zhang, L. L., Yang, C. M., et al. (2020). Lycorine inhibits tumor growth of human osteosarcoma cells by blocking Wnt/β-catenin, ERK1/2/MAPK and PI3K/AKT signaling pathway. American Journal of Translational Research, 12(9), 5381–5398.PubMedPubMedCentral
223.
Kun-Hung, S., Jui-Hsiang, H., Liao, Y.-C., Shu-Ting, T., Wu, M.-J., & Chen, P.-S. (2020). Sinomenine inhibits migration and invasion of human lung cancer cell through downregulating expression of miR-21 and MMPs. International Journal of Molecular Sciences, 21(9), 3080. https://​doi.​org/​10.​3390/​ijms21093080CrossRef
224.
Li, H. M., Lin, Z. K., Bai, Y. X., Chi, X. M., Fu, H. L., Sun, R., et al. (2017). Sinomenine inhibits ovarian cancer cell growth and metastasis by mediating the Wnt/beta-catenin pathway via targeting MCM2. RSC Advances, 7(79), 50017–50026. https://​doi.​org/​10.​1039/​c7ra10057dCrossRef
225.
226.
Lee, H., Ko, J. H., Baek, S. H., Nam, D., Lee, S. G., Lee, J., et al. (2016). Embelin inhibits invasion and migration of MDA-MB-231 breast cancer cells by suppression of CXC chemokine receptor 4, matrix metalloproteinases-9/2, and epithelial-mesenchymal transition. Phytotherapy Research, 30(6), 1021–1032. https://​doi.​org/​10.​1002/​ptr.​5612CrossRefPubMed
227.
228.
229.
Rajendran, P., Rebai Ben, A., Fatma, J. A. S., Maged Elsayed, M., Islam, M. I. H., & Saeed, Y. A. R. (2020). Thidiazuron decreases epithelial-mesenchymal transition activity through the NF-kB and PI3K/AKT signalling pathways in breast cancer. Journal of Cellular and Molecular Medicine (Online), 24(24), 14525–14538. https://​doi.​org/​10.​1111/​jcmm.​16079CrossRef
230.
Young Yun, J., Chakrabhavi, D. M., Eng, H., Narula, A. S., Namjoshi, O. A., Blough, B. E., et al. (2022). 2,3,5,6-Tetramethylpyrazine targets epithelial-mesenchymal transition by abrogating manganese superoxide dismutase expression and TGFβ-driven signaling cascades in colon cancer cells. Biomolecules, 12(7), 891. https://​doi.​org/​10.​3390/​biom12070891CrossRef
231.
232.
233.
234.
235.
236.
237.
238.
239.
240.
241.
242.
Fakhri, S., Darvish, E., Narimani, F., Moradi, S. Z., Abbaszadeh, F., & Khan, H. (2023). The regulatory role of non-coding RNAs and their interactions with phytochemicals in neurodegenerative diseases: A systematic review. Briefings in Functional Genomics, 22(2), 143–160.
243.
Fakhri, S., Iranpanah, A., Gravandi, M. M., Moradi, S. Z., Ranjbari, M., Majnooni, M. B., et al. (2021). Natural products attenuate PI3K/Akt/mTOR signaling pathway: A promising strategy in regulating neurodegeneration. Phytomedicine, 91, 153664.PubMed
244.
Fakhri, S., Moradi, S. Z., Farzaei, M. H., & Bishayee, A. (2022). Modulation of dysregulated cancer metabolism by plant secondary metabolites: A mechanistic review. In Semin Cancer Biol, (Vol. 80, pp. 276–305): Elsevier
245.
Fakhri, S., Moradi, S. Z., Nouri, Z., Cao, H., Wang, H., Khan, H., et al. (2022). Modulation of integrin receptor by polyphenols: Downstream Nrf2-Keap1/ARE and associated cross-talk mediators in cardiovascular diseases. Critical Reviews in Food Science and Nutrition, 1–25. https://​doi.​org/​10.​1080/​10408398.​2022.​2118226
246.
Fakhri, S., Moradi, S. Z., Yarmohammadi, A., Narimani, F., Wallace, C. E., & Bishayee, A. (2022). Modulation of TLR/NF-κB/NLRP signaling by bioactive phytocompounds: A promising strategy to augment cancer chemotherapy and immunotherapy. Frontiers in Oncology, 12, 834072.PubMedPubMedCentral
247.
248.
249.
250.
251.
252.
253.
254.
Xu, L., Bi, Y., Xu, Y., Zhang, Z., Xu, W., Zhang, S., et al. (2020). Oridonin inhibits the migration and epithelial-to-mesenchymal transition of small cell lung cancer cells by suppressing FAK-ERK1/2 signalling pathway. Journal of Cellular and Molecular Medicine (Online), 24(8), 4480–4493. https://​doi.​org/​10.​1111/​jcmm.​15106CrossRef
255.
256.
257.
258.
259.
Hu, J. H., Yang, D. S., Ren, X. Q., Wang, C. Y., He, Z. K., & Zhang, X. F. (2016). ArdipusillosideIinhibits the growth, invasion and epithelial-to-mesenchymal transitionof gastric cancer cells through the JAK/STAT3 signaling pathway. International Journal of Clinical and Experimental Medicine, 9(2), 1801–1807.
260.
261.
262.
Subramani, R., Gonzalez, E., Arumugam, A., Nandy, S., Gonzalez, V., Medel, J., et al. (2016). Nimbolide inhibits pancreatic cancer growth and metastasis through ROS-mediated apoptosis and inhibition of epithelial-to-mesenchymal transition. Scientific Reports (Nature Publisher Group), 6, 19819. https://​doi.​org/​10.​1038/​srep19819CrossRef
263.
264.
265.
266.
Lee, J., Hwangbo, C., Lee, J. J., Seo, J., & Lee, J. H. (2010). The sesquiterpene lactone eupatolide sensitizes breast cancer cells to TRAIL through down-regulation of c-FLIP expression. Oncology Reports, 23(1), 229–237.PubMed
267.
268.
269.
270.
271.
Jiang, S. Y., Yu, J., Zhu, M., Zhang, X. M., Zhang, Y. Y., Zhang, Q., et al. (2022). Gambogic acid inhibits epithelial-mesenchymal transition in breast cancer cells through upregulation of SIRT1 expression in vitro. Precision Medical Sciences, 11(1), 14–22. https://​doi.​org/​10.​1002/​prm2.​12057CrossRef
272.
273.
274.
275.
Cao, Z. Q., Wang, X. X., Lu, L., Xu, J. W., Li, X. B., Zhang, G. R., et al. (2018). β-Sitosterol and gemcitabine exhibit synergistic anti-pancreatic cancer activity by modulating apoptosis and inhibiting epithelial-mesenchymal transition by deactivating Akt/GSK-3β signaling. Frontiers in Pharmacology, 9, 1525. https://​doi.​org/​10.​3389/​fphar.​2018.​01525CrossRefPubMed
276.
277.
278.
279.
280.
281.
282.
283.
Ghanbari-Movahed, M., Mondal, A., Farzaei, M. H., & Bishayee, A. (2022). Quercetin-and rutin-based nano-formulations for cancer treatment: A systematic review of improved efficacy and molecular mechanisms. Phytomedicine, 97, 153909.PubMed
284.
Ghanbari-Movahed, M., Kaceli, T., Mondal, A., Farzaei, M. H., & Bishayee, A. (2021). Recent advances in improved anticancer efficacies of camptothecin nano-formulations: A systematic review. Biomedicines, 9(5), 480.PubMedPubMedCentral
285.
Kashyap, D., Tuli, H. S., Yerer, M. B., Sharma, A., Sak, K., Srivastava, S., et al. (2021). Natural product-based nanoformulations for cancer therapy: Opportunities and challenges. In Semin Cancer Biol, (Vol. 69, pp. 5–23): Elsevier
286.
Lagoa, R., Silva, J., Rodrigues, J. R., & Bishayee, A. (2020). Advances in phytochemical delivery systems for improved anticancer activity. Biotechnology Advances, 38, 107382.PubMed
Metadata
Title
Targeting the key players of phenotypic plasticity in cancer cells by phytochemicals
Authors
Sajad Fakhri
Seyed Zachariah Moradi
Fatemeh Abbaszadeh
Farahnaz Faraji
Roshanak Amirian
Dona Sinha
Emily G. McMahon
Anupam Bishayee
Publication date
03-01-2024
Publisher
Springer US
Keyword
Metastasis
Published in
Cancer and Metastasis Reviews / Issue 1/2024
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-023-10161-8

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