Skip to main content
Top
Published in: BMC Complementary Medicine and Therapies 1/2022

Open Access 01-12-2022 | Breast Cancer | Research

Naringenin and cryptotanshinone shift the immune response towards Th1 and modulate T regulatory cells via JAK2/STAT3 pathway in breast cancer

Authors: Shokoofe Noori, Mitra Nourbakhsh, Hossein Imani, Niloofar Deravi, Niloufar Salehi, Zohreh Abdolvahabi

Published in: BMC Complementary Medicine and Therapies | Issue 1/2022

Login to get access

Abstract

Background

Use of natural products has been proposed as an efficient method in modulation of immune system and treatment of cancers. The aim of this study was to investigate the potential of cryptotanshinone (CPT), naringenin, and their combination in modulating the immune response towards Th1 cells and the involvement of JAK2/STAT3 signaling pathway in these effects.

Methods

Mouse models of delayed type hypersensitivity (DTH) were produced and treated with naringenin and CPT. The proliferation of spleen cells were assessed by Bromodeoxyuridine (BrdU) assay. Flowcytometry and enzyme-linked immunosorbent assay (ELISA) tests were employed to evaluate subpopulation of T-lymphocytes and the levels of cytokines, respectively. The JAK/STAT signaling pathway was analyzed by Western blotting.

Results

We showed higher DTH, increased lymphocyte proliferation, decreased tumor growth and reduced JAK2/STAT3 phosphorylation in mice treated with naringenin and CPT. Moreover, a significant decline in the production of IL-4 and an upsurge in the production of IFN-γ by splenocytes were observed. Additionally, the population of intra-tumor CD4+CD25+Foxp3+ T cells was significantly lower in naringenin + CPT treated animals than that in controls.

Conclusion

Naringenin-CPT combination could exert immunomodulatory effects, suggesting this combination as a novel complementary therapeutic regimen for breast cancer.
Appendix
Available only for authorised users
Literature
1.
go back to reference Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J Clin. 2018;68(6):394–424. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J Clin. 2018;68(6):394–424.
2.
go back to reference Rebecca S, Siegel M, Kimberly D, Miller M, Ahmedin JD. Cancer statistics. Ca Cancer J Clin. 2017;67(27):7–30. Rebecca S, Siegel M, Kimberly D, Miller M, Ahmedin JD. Cancer statistics. Ca Cancer J Clin. 2017;67(27):7–30.
3.
go back to reference Ginsburg O, Bray F, Coleman MP, Vanderpuye V, Eniu A, Kotha SR, et al. The global burden of women’s cancers: a grand challenge in global health. Lancet. 2017;389(10071):847–60.PubMedCrossRef Ginsburg O, Bray F, Coleman MP, Vanderpuye V, Eniu A, Kotha SR, et al. The global burden of women’s cancers: a grand challenge in global health. Lancet. 2017;389(10071):847–60.PubMedCrossRef
5.
go back to reference Li W, Saud SM, Young MR, Colburn NH, Hua B. Cryptotanshinone, a Stat3 inhibitor, suppresses colorectal cancer proliferation and growth in vitro. Mol Cell Biochem. 2015;406(1–2):63–73.PubMedCrossRef Li W, Saud SM, Young MR, Colburn NH, Hua B. Cryptotanshinone, a Stat3 inhibitor, suppresses colorectal cancer proliferation and growth in vitro. Mol Cell Biochem. 2015;406(1–2):63–73.PubMedCrossRef
6.
go back to reference Patel K, Singh GK, Patel DK. A review on pharmacological and analytical aspects of naringenin. Chin J Integr Med. 2018;24(7):551–60.PubMedCrossRef Patel K, Singh GK, Patel DK. A review on pharmacological and analytical aspects of naringenin. Chin J Integr Med. 2018;24(7):551–60.PubMedCrossRef
7.
go back to reference Chun-Yan S, Qian-Liang M, Rahman K, Ting H, Lu-Ping Q. Salvia miltiorrhiza: traditional medicinal uses, chemistry, and pharmacology. Chin J Nat Med. 2015;13(3):163–82. Chun-Yan S, Qian-Liang M, Rahman K, Ting H, Lu-Ping Q. Salvia miltiorrhiza: traditional medicinal uses, chemistry, and pharmacology. Chin J Nat Med. 2015;13(3):163–82.
8.
go back to reference Kim DH, Paudel P, Yu T, Ngo TM, Kim JA, Jung HA, et al. Characterization of the inhibitory activity of natural tanshinones from Salvia miltiorrhiza roots on protein tyrosine phosphatase 1B. Chem Biol Interact. 2017;278:65–73.PubMedCrossRef Kim DH, Paudel P, Yu T, Ngo TM, Kim JA, Jung HA, et al. Characterization of the inhibitory activity of natural tanshinones from Salvia miltiorrhiza roots on protein tyrosine phosphatase 1B. Chem Biol Interact. 2017;278:65–73.PubMedCrossRef
9.
go back to reference Park B, Song HS, Kwon JE, Cho SM, Jang S-A, Kim MY, et al. Effects of Salvia miltiorrhiza extract with supplemental liquefied calcium on osteoporosis in calcium-deficient ovariectomized mice. BMC Complement Altern Med. 2017;17(1):545.PubMedPubMedCentralCrossRef Park B, Song HS, Kwon JE, Cho SM, Jang S-A, Kim MY, et al. Effects of Salvia miltiorrhiza extract with supplemental liquefied calcium on osteoporosis in calcium-deficient ovariectomized mice. BMC Complement Altern Med. 2017;17(1):545.PubMedPubMedCentralCrossRef
10.
go back to reference Li S, Wang H, Hong L, Liu W, Huang F, Wang J, et al. Cryptotanshinone inhibits breast cancer cell growth by suppressing estrogen receptor signaling. Cancer Biol Ther. 2015;16(1):176–84.PubMedCrossRef Li S, Wang H, Hong L, Liu W, Huang F, Wang J, et al. Cryptotanshinone inhibits breast cancer cell growth by suppressing estrogen receptor signaling. Cancer Biol Ther. 2015;16(1):176–84.PubMedCrossRef
11.
go back to reference Chen Z, Zhu R, Zheng J, Chen C, Huang C, Ma J, et al. Cryptotanshinone inhibits proliferation yet induces apoptosis by suppressing STAT3 signals in renal cell carcinoma. Oncotarget. 2017;8(30):50023.PubMedPubMedCentralCrossRef Chen Z, Zhu R, Zheng J, Chen C, Huang C, Ma J, et al. Cryptotanshinone inhibits proliferation yet induces apoptosis by suppressing STAT3 signals in renal cell carcinoma. Oncotarget. 2017;8(30):50023.PubMedPubMedCentralCrossRef
12.
go back to reference Li H, Gao C, Liu C, Liu L, Zhuang J, Yang J, et al. A review of the biological activity and pharmacology of cryptotanshinone, an important active constituent in Danshen. Biomed Pharmacother. 2021;137: 111332.PubMedCrossRef Li H, Gao C, Liu C, Liu L, Zhuang J, Yang J, et al. A review of the biological activity and pharmacology of cryptotanshinone, an important active constituent in Danshen. Biomed Pharmacother. 2021;137: 111332.PubMedCrossRef
14.
go back to reference Waldman AD, Fritz JM, Lenardo MJ. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat Rev Immunol. 2020;20(11):651–68.PubMedPubMedCentralCrossRef Waldman AD, Fritz JM, Lenardo MJ. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat Rev Immunol. 2020;20(11):651–68.PubMedPubMedCentralCrossRef
15.
16.
go back to reference Franciotta D, Zardini E, Bergamaschi R, Andreoni L, Cosi V. Interferon γ and interleukin 4 producing T cells in peripheral blood of multiple sclerosis patients undergoing immunomodulatory treatment. J Neurol Neurosurg Psychiatry. 2003;74(1):123–6.PubMedPubMedCentralCrossRef Franciotta D, Zardini E, Bergamaschi R, Andreoni L, Cosi V. Interferon γ and interleukin 4 producing T cells in peripheral blood of multiple sclerosis patients undergoing immunomodulatory treatment. J Neurol Neurosurg Psychiatry. 2003;74(1):123–6.PubMedPubMedCentralCrossRef
17.
go back to reference Noori S, Taghikhani M, M. Hassan Z, Allameh A, Mostafaei A. Tehranolide Could Shift the Immune Response towards Th1 and Modulate the Intra-Tumor Infiltrated T Regulatory Cells. Iran J Immunol. 2009;6(4):216–24.PubMed Noori S, Taghikhani M, M. Hassan Z, Allameh A, Mostafaei A. Tehranolide Could Shift the Immune Response towards Th1 and Modulate the Intra-Tumor Infiltrated T Regulatory Cells. Iran J Immunol. 2009;6(4):216–24.PubMed
18.
go back to reference Ito SE, Shirota H, Kasahara Y, Saijo K, Ishioka C. IL-4 blockade alters the tumor microenvironment and augments the response to cancer immunotherapy in a mouse model. Cancer Immunol Immunother. 2017;66(11):1485–96.PubMedCrossRef Ito SE, Shirota H, Kasahara Y, Saijo K, Ishioka C. IL-4 blockade alters the tumor microenvironment and augments the response to cancer immunotherapy in a mouse model. Cancer Immunol Immunother. 2017;66(11):1485–96.PubMedCrossRef
20.
go back to reference Verma A, Mathur R, Farooque A, Kaul V, Gupta S, Dwarakanath BS. T-regulatory cells in tumor progression and therapy. Cancer Manag Res. 2019;11:10731–47.PubMedPubMedCentralCrossRef Verma A, Mathur R, Farooque A, Kaul V, Gupta S, Dwarakanath BS. T-regulatory cells in tumor progression and therapy. Cancer Manag Res. 2019;11:10731–47.PubMedPubMedCentralCrossRef
21.
go back to reference Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol. 2006;6(4):295–307.PubMedCrossRef Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol. 2006;6(4):295–307.PubMedCrossRef
22.
go back to reference Sredni B, Tichler T, Shani A, Catane R, Kaufman B, Strassmann G, et al. Predominance of TH1 response in tumor-bearing mice and cancer patients treated with AS 101. J Natl Cancer Inst. 1996;88:1276–84.PubMedCrossRef Sredni B, Tichler T, Shani A, Catane R, Kaufman B, Strassmann G, et al. Predominance of TH1 response in tumor-bearing mice and cancer patients treated with AS 101. J Natl Cancer Inst. 1996;88:1276–84.PubMedCrossRef
23.
go back to reference Jin W. Role of JAK/STAT3 signaling in the regulation of metastasis, the transition of cancer stem cells, and chemoresistance of cancer by epithelial-mesenchymal transition. Cells. 2020;9(1):217.PubMedCentralCrossRef Jin W. Role of JAK/STAT3 signaling in the regulation of metastasis, the transition of cancer stem cells, and chemoresistance of cancer by epithelial-mesenchymal transition. Cells. 2020;9(1):217.PubMedCentralCrossRef
24.
go back to reference Marotta LL, Almendro V, Marusyk A, Shipitsin M, Schemme J, Walker SR, et al. The JAK2/STAT3 signaling pathway is required for growth of CD44+CD24ˉ stem cell-like breast cancer cells in human tumors. J Clin Investig. 2011;121(7):2723–35.PubMedPubMedCentralCrossRef Marotta LL, Almendro V, Marusyk A, Shipitsin M, Schemme J, Walker SR, et al. The JAK2/STAT3 signaling pathway is required for growth of CD44+CD24ˉ stem cell-like breast cancer cells in human tumors. J Clin Investig. 2011;121(7):2723–35.PubMedPubMedCentralCrossRef
25.
go back to reference Kitamura H, Ohno Y, Toyoshima Y, Ohtake J, Homma S, Kawamura H, et al. Interleukin-6/STAT3 signaling as a promising target to improve the efficacy of cancer immunotherapy. Cancer Sci. 2017;108(10):1947–52.PubMedPubMedCentralCrossRef Kitamura H, Ohno Y, Toyoshima Y, Ohtake J, Homma S, Kawamura H, et al. Interleukin-6/STAT3 signaling as a promising target to improve the efficacy of cancer immunotherapy. Cancer Sci. 2017;108(10):1947–52.PubMedPubMedCentralCrossRef
26.
go back to reference Pallandre JR, Brillard E, Créhange G, Radlovic A, Remy-Martin JP, Saas P, et al. Role of STAT3 in CD4+CD25+FOXP3+ regulatory lymphocyte generation: implications in graft-versus-host disease and antitumor immunity. J immunol (Baltimore, Md : 1950). 2007;179(11):7593–604. Pallandre JR, Brillard E, Créhange G, Radlovic A, Remy-Martin JP, Saas P, et al. Role of STAT3 in CD4+CD25+FOXP3+ regulatory lymphocyte generation: implications in graft-versus-host disease and antitumor immunity. J immunol (Baltimore, Md : 1950). 2007;179(11):7593–604.
27.
go back to reference Lee H, Pal SK, Reckamp K, Figlin RA, Yu H. STAT3: a target to enhance antitumor immune response. Curr Top Microbiol Immunol. 2011;344:41–59. Lee H, Pal SK, Reckamp K, Figlin RA, Yu H. STAT3: a target to enhance antitumor immune response. Curr Top Microbiol Immunol. 2011;344:41–59.
28.
go back to reference Qin J-J, Yan L, Zhang J, Zhang W-D. STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review. J Exp Clin Cancer Res. 2019;38(1):195.PubMedPubMedCentralCrossRef Qin J-J, Yan L, Zhang J, Zhang W-D. STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review. J Exp Clin Cancer Res. 2019;38(1):195.PubMedPubMedCentralCrossRef
29.
go back to reference Yu H, Jove R. The STATs of cancer—new molecular targets come of age. Nat Rev Cancer. 2004;4(2):97–105.PubMedCrossRef Yu H, Jove R. The STATs of cancer—new molecular targets come of age. Nat Rev Cancer. 2004;4(2):97–105.PubMedCrossRef
30.
go back to reference Nourbakhsh M, Farzaneh S, Taghikhani A, Zarghi A, Noori S. The effect of a newly synthesized ferrocene derivative against MCF-7 breast cancer cells and spheroid stem cells through ROS production and inhibition of JAK2/STAT3 signaling pathway. Anticancer Agents Med Chem. 2020;20(7):875–86.PubMedCrossRef Nourbakhsh M, Farzaneh S, Taghikhani A, Zarghi A, Noori S. The effect of a newly synthesized ferrocene derivative against MCF-7 breast cancer cells and spheroid stem cells through ROS production and inhibition of JAK2/STAT3 signaling pathway. Anticancer Agents Med Chem. 2020;20(7):875–86.PubMedCrossRef
31.
go back to reference Afshari H, Nourbakhsh M, Salehi N, Mahboubi-Rabbani M, Zarghi A, Noori S. STAT3-mediated apoptotic-enhancing function of sclareol against breast cancer cells and cell sensitization to cyclophosphamide. Iran J Pharm Res. 2020;19(1):398–412.PubMedPubMedCentral Afshari H, Nourbakhsh M, Salehi N, Mahboubi-Rabbani M, Zarghi A, Noori S. STAT3-mediated apoptotic-enhancing function of sclareol against breast cancer cells and cell sensitization to cyclophosphamide. Iran J Pharm Res. 2020;19(1):398–412.PubMedPubMedCentral
32.
go back to reference Council NR. Guide for the Care and Use of Laboratory Animals. 8th ed. Washington, DC: The National Academies Press; 2011. p. 246. Council NR. Guide for the Care and Use of Laboratory Animals. 8th ed. Washington, DC: The National Academies Press; 2011. p. 246.
33.
go back to reference du PercieSert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLOS Biology. 2020;18(7):e3000410.CrossRef du PercieSert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLOS Biology. 2020;18(7):e3000410.CrossRef
34.
go back to reference Langroudi L, Hasan Z, Ardeshirylajimi A, Soleimani M. Isolation and characterization of a new cell line from spontaneous mouse mammary tumour, MBL-6, for in vivo cancer studies. Vet Sci Dev. 2017;7(1):6042. Langroudi L, Hasan Z, Ardeshirylajimi A, Soleimani M. Isolation and characterization of a new cell line from spontaneous mouse mammary tumour, MBL-6, for in vivo cancer studies. Vet Sci Dev. 2017;7(1):6042.
35.
go back to reference Noori S, Taghikhani M, Hassan ZM, Allameha A, Mostafaei A. Tehranolide molecule modulates the immune response, reduce regulatory T cell and inhibits tumor growth in vivo. Mol Immunol. 2010;47(7):1579–84.PubMedCrossRef Noori S, Taghikhani M, Hassan ZM, Allameha A, Mostafaei A. Tehranolide molecule modulates the immune response, reduce regulatory T cell and inhibits tumor growth in vivo. Mol Immunol. 2010;47(7):1579–84.PubMedCrossRef
36.
go back to reference Gad SC, Cassidy CD, Aubert N, Spainhour B, Robbe H. Nonclinical Vehicle Use in Studies by Multiple Routes in Multiple Species. Int J Toxicol. 2006;25(6):499–521.PubMedCrossRef Gad SC, Cassidy CD, Aubert N, Spainhour B, Robbe H. Nonclinical Vehicle Use in Studies by Multiple Routes in Multiple Species. Int J Toxicol. 2006;25(6):499–521.PubMedCrossRef
37.
go back to reference Cragg GM, Pezzuto JM. natural products as a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents. Med Princ Pract. 2016;25(suppl 2 Suppl. 2):41–59.PubMedCrossRef Cragg GM, Pezzuto JM. natural products as a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents. Med Princ Pract. 2016;25(suppl 2 Suppl. 2):41–59.PubMedCrossRef
38.
go back to reference Shin DS, Kim HN, Shin KD, Yoon YJ, Kim SJ, Han DC, et al. Cryptotanshinone inhibits constitutive signal transducer and activator of transcription 3 function through blocking the dimerization in DU145 prostate cancer cells. Cancer Res. 2009;69(1):193–202.PubMedCrossRef Shin DS, Kim HN, Shin KD, Yoon YJ, Kim SJ, Han DC, et al. Cryptotanshinone inhibits constitutive signal transducer and activator of transcription 3 function through blocking the dimerization in DU145 prostate cancer cells. Cancer Res. 2009;69(1):193–202.PubMedCrossRef
39.
go back to reference Bao L, Liu F, Guo HB, Li Y, Tan BB, Zhang WX, et al. Naringenin inhibits proliferation, migration, and invasion as well as induces apoptosis of gastric cancer SGC7901 cell line by downregulation of AKT pathway. Tumour Biol. 2016;37(8):11365–74.PubMedCrossRef Bao L, Liu F, Guo HB, Li Y, Tan BB, Zhang WX, et al. Naringenin inhibits proliferation, migration, and invasion as well as induces apoptosis of gastric cancer SGC7901 cell line by downregulation of AKT pathway. Tumour Biol. 2016;37(8):11365–74.PubMedCrossRef
40.
go back to reference Chen L, Wang H-J, Xie W, Yao Y, Zhang Y-S, Wang H. Cryptotanshinone inhibits lung tumorigenesis and induces apoptosis in cancer cells in vitro and in vivo. Mol Med Rep. 2014;9(6):2447–52.PubMedCrossRef Chen L, Wang H-J, Xie W, Yao Y, Zhang Y-S, Wang H. Cryptotanshinone inhibits lung tumorigenesis and induces apoptosis in cancer cells in vitro and in vivo. Mol Med Rep. 2014;9(6):2447–52.PubMedCrossRef
41.
go back to reference Gumushan Aktas H, Akgun T. Naringenin inhibits prostate cancer metastasis by blocking voltage-gated sodium channels. Biomed Pharmacother. 2018;106:770–5.PubMedCrossRef Gumushan Aktas H, Akgun T. Naringenin inhibits prostate cancer metastasis by blocking voltage-gated sodium channels. Biomed Pharmacother. 2018;106:770–5.PubMedCrossRef
42.
go back to reference Liu Y, Lin F, Chen Y, Wang R, Liu J, Jin Y, et al. Cryptotanshinone inhibites bladder cancer cell proliferation and promotes apoptosis via the PTEN/PI3K/AKT Pathway. J Cancer. 2020;11(2):488–99.PubMedPubMedCentralCrossRef Liu Y, Lin F, Chen Y, Wang R, Liu J, Jin Y, et al. Cryptotanshinone inhibites bladder cancer cell proliferation and promotes apoptosis via the PTEN/PI3K/AKT Pathway. J Cancer. 2020;11(2):488–99.PubMedPubMedCentralCrossRef
43.
go back to reference Parashar P, Tripathi CB, Arya M, Kanoujia J, Singh M, Yadav A, et al. Biotinylated naringenin intensified anticancer effect of gefitinib in urethane-induced lung cancer in rats: favourable modulation of apoptotic regulators and serum metabolomics. Artif Cells Nanomed Biotechnol. 2018;46(sup3):S598-s610.PubMedCrossRef Parashar P, Tripathi CB, Arya M, Kanoujia J, Singh M, Yadav A, et al. Biotinylated naringenin intensified anticancer effect of gefitinib in urethane-induced lung cancer in rats: favourable modulation of apoptotic regulators and serum metabolomics. Artif Cells Nanomed Biotechnol. 2018;46(sup3):S598-s610.PubMedCrossRef
44.
go back to reference Wu CF, Klauck SM, Efferth T. Anticancer activity of cryptotanshinone on acute lymphoblastic leukemia cells. Arch Toxicol. 2016;90(9):2275–86.PubMedCrossRef Wu CF, Klauck SM, Efferth T. Anticancer activity of cryptotanshinone on acute lymphoblastic leukemia cells. Arch Toxicol. 2016;90(9):2275–86.PubMedCrossRef
45.
go back to reference Tan X, Chen W, Jiao C, Liang H, Yun H, He C, et al. Anti-tumor and immunomodulatory activity of the aqueous extract of Sarcodon imbricatus in vitro and in vivo. Food Funct. 2020;11(1):1110–21.PubMedCrossRef Tan X, Chen W, Jiao C, Liang H, Yun H, He C, et al. Anti-tumor and immunomodulatory activity of the aqueous extract of Sarcodon imbricatus in vitro and in vivo. Food Funct. 2020;11(1):1110–21.PubMedCrossRef
46.
go back to reference Chen C, Su X, Hu Z. Immune promotive effect of bioactive peptides may be mediated by regulating the expression of SOCS1/miR-155. Exp Ther Med. 2019;18(3):1850–62.PubMedPubMedCentral Chen C, Su X, Hu Z. Immune promotive effect of bioactive peptides may be mediated by regulating the expression of SOCS1/miR-155. Exp Ther Med. 2019;18(3):1850–62.PubMedPubMedCentral
47.
go back to reference Lian GY, Wang QM, Tang PM, Zhou S, Huang XR, Lan HY. Combination of Asiatic Acid and Naringenin Modulates NK Cell Anti-cancer Immunity by Rebalancing Smad3/Smad7 Signaling. Mol Ther. 2018;26(9):2255–66.PubMedPubMedCentralCrossRef Lian GY, Wang QM, Tang PM, Zhou S, Huang XR, Lan HY. Combination of Asiatic Acid and Naringenin Modulates NK Cell Anti-cancer Immunity by Rebalancing Smad3/Smad7 Signaling. Mol Ther. 2018;26(9):2255–66.PubMedPubMedCentralCrossRef
48.
go back to reference Casey SC, Amedei A, Aquilano K, Azmi AS, Benencia F, Bhakta D, et al. Cancer prevention and therapy through the modulation of the tumor microenvironment. Semin Cancer Biol. 2015;35:S199–223.PubMedPubMedCentralCrossRef Casey SC, Amedei A, Aquilano K, Azmi AS, Benencia F, Bhakta D, et al. Cancer prevention and therapy through the modulation of the tumor microenvironment. Semin Cancer Biol. 2015;35:S199–223.PubMedPubMedCentralCrossRef
50.
go back to reference Castro F, Cardoso AP, Gonçalves RM, Serre K, Oliveira MJ. Interferon-gamma at the crossroads of tumor immune surveillance or evasion. Front Immunol. 2018;9:847.PubMedPubMedCentralCrossRef Castro F, Cardoso AP, Gonçalves RM, Serre K, Oliveira MJ. Interferon-gamma at the crossroads of tumor immune surveillance or evasion. Front Immunol. 2018;9:847.PubMedPubMedCentralCrossRef
51.
go back to reference Mendes LF, Gaspar VM, Conde TA, Mano JF, Duarte IF. Flavonoid-mediated immunomodulation of human macrophages involves key metabolites and metabolic pathways. Sci Rep. 2019;9(1):14906.PubMedPubMedCentralCrossRef Mendes LF, Gaspar VM, Conde TA, Mano JF, Duarte IF. Flavonoid-mediated immunomodulation of human macrophages involves key metabolites and metabolic pathways. Sci Rep. 2019;9(1):14906.PubMedPubMedCentralCrossRef
52.
go back to reference Qin L, Jin L, Lu L, Lu X, Zhang C, Zhang F, et al. Naringenin reduces lung metastasis in a breast cancer resection model. Protein Cell. 2011;2(6):507–16.PubMedPubMedCentralCrossRef Qin L, Jin L, Lu L, Lu X, Zhang C, Zhang F, et al. Naringenin reduces lung metastasis in a breast cancer resection model. Protein Cell. 2011;2(6):507–16.PubMedPubMedCentralCrossRef
53.
go back to reference Du G, Jin L, Han X, Song Z, Zhang H, Liang W. Naringenin: a potential immunomodulator for inhibiting lung fibrosis and metastasis. Cancer Res. 2009;69(7):3205–12.PubMedCrossRef Du G, Jin L, Han X, Song Z, Zhang H, Liang W. Naringenin: a potential immunomodulator for inhibiting lung fibrosis and metastasis. Cancer Res. 2009;69(7):3205–12.PubMedCrossRef
54.
go back to reference Wiejak J, Dunlop J, Mackay SP, Yarwood SJ. Flavanoids induce expression of the suppressor of cytokine signalling 3 (SOCS3) gene and suppress IL-6-activated signal transducer and activator of transcription 3 (STAT3) activation in vascular endothelial cells. Biochem J. 2013;454(2):283–93.PubMedCrossRef Wiejak J, Dunlop J, Mackay SP, Yarwood SJ. Flavanoids induce expression of the suppressor of cytokine signalling 3 (SOCS3) gene and suppress IL-6-activated signal transducer and activator of transcription 3 (STAT3) activation in vascular endothelial cells. Biochem J. 2013;454(2):283–93.PubMedCrossRef
55.
go back to reference Ge Y, Yang B, Chen Z, Cheng R. Cryptotanshinone suppresses the proliferation and induces the apoptosis of pancreatic cancer cells via the STAT3 signaling pathway. Mol Med Rep. 2015;12(5):7782–8.PubMedCrossRef Ge Y, Yang B, Chen Z, Cheng R. Cryptotanshinone suppresses the proliferation and induces the apoptosis of pancreatic cancer cells via the STAT3 signaling pathway. Mol Med Rep. 2015;12(5):7782–8.PubMedCrossRef
56.
go back to reference Wiejak J, Dunlop J, Mackay S, Yarwood S. Flavanoids Induce Expression of the Suppressor of Cytokine Signalling 3 (SOCS3) Gene and Suppress IL6- Activated Signal Transducer and Activator of Transcription 3 (STAT3) Activation in Vascular Endothelial Cells. Biochem J. 2013;454(2):283–93.PubMedCrossRef Wiejak J, Dunlop J, Mackay S, Yarwood S. Flavanoids Induce Expression of the Suppressor of Cytokine Signalling 3 (SOCS3) Gene and Suppress IL6- Activated Signal Transducer and Activator of Transcription 3 (STAT3) Activation in Vascular Endothelial Cells. Biochem J. 2013;454(2):283–93.PubMedCrossRef
57.
go back to reference Lee J-K, Won C, Yi EH, Seok S-H, Kim M-H, Kim S-J, et al. Signal transducer and activator of transcription 3 (Stat3) contributes to T-cell homeostasis by regulating pro-survival Bcl-2 family genes. Immunology. 2013;140(3):288–300.PubMedPubMedCentral Lee J-K, Won C, Yi EH, Seok S-H, Kim M-H, Kim S-J, et al. Signal transducer and activator of transcription 3 (Stat3) contributes to T-cell homeostasis by regulating pro-survival Bcl-2 family genes. Immunology. 2013;140(3):288–300.PubMedPubMedCentral
58.
go back to reference Dzhagalov I, Dunkle A, He Y-W. The anti-apoptotic Bcl-2 family member Mcl-1 promotes T lymphocyte survival at multiple stages. J Immunol (Baltimore, Md : 1950). 2008;181(1):521–8. Dzhagalov I, Dunkle A, He Y-W. The anti-apoptotic Bcl-2 family member Mcl-1 promotes T lymphocyte survival at multiple stages. J Immunol (Baltimore, Md : 1950). 2008;181(1):521–8.
Metadata
Title
Naringenin and cryptotanshinone shift the immune response towards Th1 and modulate T regulatory cells via JAK2/STAT3 pathway in breast cancer
Authors
Shokoofe Noori
Mitra Nourbakhsh
Hossein Imani
Niloofar Deravi
Niloufar Salehi
Zohreh Abdolvahabi
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2022
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-022-03625-x

Other articles of this Issue 1/2022

BMC Complementary Medicine and Therapies 1/2022 Go to the issue