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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2020

Open Access 01-12-2020 | Breast Cancer | Research article

Cell metabolomics to study the function mechanism of Cyperus rotundus L. on triple-negative breast cancer cells

Authors: Shuangshuang Ma, Fukai Wang, Caijuan Zhang, Xinzhao Wang, Xueyong Wang, Zhiyong Yu

Published in: BMC Complementary Medicine and Therapies | Issue 1/2020

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Abstract

Background

Triple-negative breast cancer (TNBC) is a kind of malignant tumor with higher recurrence and metastasis rate. According to historical records, the dry rhizomes Cyperus rotundus L. could be ground into powder and mixed with ginger juice and wine for external application for breast cancer. We studied the effect of the ethanol extract of Cyperus rotundus L. (EECR) on TNBC cells and found its’ apoptosis-inducing effect with a dose-relationship. But the function mechanism of EECR on TNBC is still mysterious. Hence, the present research aimed to detect its function mechanism at the small molecule level through ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) metabolomics.

Methods

The CCK-8 assay and the Annexin V-FITC/PI assay were applied to test the effect of EECR on MDA-MB-231 cells and MDA-MB 468 cells at various concentrations of 0, 200, 400, and 600 μg/ml. UPLC-Q-TOF-MS/MS based metabolomics was used between the control group and the EECR treatment groups. Multivariate statistical analysis was used to visualize the apoptosis-inducing action of EECR and filtrate significantly changed metabolites.

Results

The apoptosis-inducing action was confirmed and forty-nine significantly changed metabolites (VIP > 1, p < 0.05, and FC > 1.2 or FC < 0.8) were identified after the interference of EECR. The level of significant differential metabolites between control group, middle dose group, and high dose group were compared and found that which supported the apoptosis-inducing action with dose-dependence.

Conclusion

By means of metabolism, we have detected the mechanism of EECR inducing apoptosis of TNBC cells at the level of small molecule metabolites and found that EECR impacted the energy metabolism of TNBC cells. In addition, we concluded that EECR induced apoptosis by breaking the balance between ATP-production and ATP-consumption: arresting the pathways of Carbohydrate metabolism such as Central carbon metabolism in cancer, aerobic glycolysis, and Amino sugar and nucleotide sugar metabolism, whereas accelerating the pathways of ATP-consumption including Amino Acids metabolism, Fatty acid metabolism, Riboflavin metabolism and Purine metabolism. Although further study is still needed, EECR has great potential in the clinical treatment of TNBC with fewer toxic and side effects.
Appendix
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Literature
1.
Schneider BP, Winer EP, Foulkes WD, Judy G, Perou CM, Andrea R, Sledge GW, Carey LA. Triple-negative breast cancer: risk factors to potential targets. Clin Cancer Res. 2008;14(24):8010.PubMed
2.
Foulkes WD, Smith IE, Reisfilho JS. Triple-negative breast Cancer — NEJM; 2010.
3.
Narod SA. Breast cancer in young women. Nat Rev Clin Oncol. 2012;9(8):460–70.PubMed
4.
Young SR, Pilarski RT, Donenberg T, Shapiro C, Hammond LS, Miller J, Brooks KA, Cohen S, Tenenholz B, Desai D. The prevalence of BRCA1 mutations among young women with triple-negative breast cancer. BMC Cancer. 2009;9(1):86.PubMedPubMedCentral
5.
Bowen RL, Duffy SW, Ryan DA, Hart IR, Jones JL. Early onset of breast cancer in a group of British black women. Br J Cancer. 2008;98(8):1482 author reply 1483.
6.
Suryavanshi S, Choudhari A, Raina P, Kaul-Ghanekar R. A polyherbal formulation, HC9 regulated cell growth and expression of cell cycle and chromatin modulatory proteins in breast cancer cell lines. J Ethnopharmacol. 2019;242:10.
7.
Park SE, Shin WT, Park C, Hong SH, Kim GY, Kim SO, Ryu CH, Hong SH, Choi YH. Induction of apoptosis in MDA-MB-231 human breast carcinoma cells with an ethanol extract of Cyperus rotundus L. by activating caspases. Oncol Rep. 2014;32(6):2461–70.PubMed
8.
Mannarreddy P, Denis M, Munireddy D, Pandurangan R, Thangavelu KP, Venkatesan K. Cytotoxic effect of Cyperus rotundus rhizome extract on human cancer cell lines. Biomed Pharmacother. 2017;95:1375–87.PubMed
9.
Pirzada AM, Ali HH, Naeem M, Latif M, Bukhari AH, Tanveer A. Cyperus rotundus L.: traditional uses, phytochemistry, and pharmacological activities. J Ethnopharmacol. 2015;174:540–60.PubMed
10.
Wang FK, Song X, Ma SS, Liu CY, Sun XH, Wang XZ, Liu ZY, Liang D, Yu ZY. The treatment role of Cyperus rotundus L to triple-negative breast cancer cells. Biosci Rep. 2019;39:12.
11.
Patti GJ, Yanes O, Siuzdak G. Metabolomics: the apogee of the omic triology. Nat Rev Mol Cell Biol. 2013;13(4):263.
12.
Peterson AL, Walker AK, Sloan EK, Creek DJ. Optimized method for untargeted metabolomics analysis of MDA-MB-231 breast Cancer cells. Metabolites. 2016;6(4):16.
13.
Hounoum BM, Blasco H, Emond P, Mavel S. Liquid chromatography-high-resolution mass spectrometry-based cell metabolomics: experimental design, recommendations, and applications. Trac-Trends Anal Chem. 2016;75:118–28.
14.
Hayton S, Maker GL, Mullaney I, Trengove RD. Experimental design and reporting standards for metabolomics studies of mammalian cell lines. Cell Mol Life Sci. 2017;74(24):4421–41.PubMed
15.
Sangster T, Major H, Plumb R, Wilson AJ, Wilson ID. A pragmatic and readily implemented quality control strategy for HPLC-MS and GC-MS-based metabonomic analysis. Analyst. 2006;131(10):1075–8.PubMed
16.
Roberts LS, Yan P, Bateman LA, Nomura DK. Mapping novel metabolic nodes targeted by anti-Cancer drugs that impair triple-negative breast Cancer pathogenicity. ACS Chem Biol. 2017;12(4):1133–40.PubMed
17.
Dyczynski M, Vesterlund M, Bjorklund AC, Zachariadis V, Janssen J, Gallart-Ayala H, Daskalaki E, Wheelock CE, Lehtio J, Grander D, et al. Metabolic reprogramming of acute lymphoblastic leukemia cells in response to glucocorticoid treatment. Cell Death Dis. 2018;9:13.
18.
Zelena E, Dunn WB, Broadhurst D, Francis-McIntyre S, Carroll KM, Begley P, O'Hagan S, Knowles JD, Halsall A, Wilson ID, et al. Development of a robust and repeatable UPLC-MS method for the Long-term Metabolomic study of human serum. Anal Chem. 2009;81(4):1357–64.PubMed
19.
Heiden MGV, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324(5930):1029–33.
20.
Koppenol WH, Bounds PL, Dang CV. Otto Warburg's contributions to current concepts of cancer metabolism. Nat Rev Cancer. 2011;11(5):325–37.PubMed
21.
Chen JQ, Russo J. Dysregulation of glucose transport, glycolysis, TCA cycle and glutaminolysis by oncogenes and tumor suppressors in cancer cells. Biochim Biophys Acta-Rev Cancer. 2012;1826(2):370–84.
22.
Icard P, Poulain L, Lincet H. Understanding the central role of citrate in the metabolism of cancer cells. Biochim Biophys Acta-Rev Cancer. 2012;1825(1):111–6.
23.
Saravana Perumal S, Shanthi P, Sachdanandam P. Energy-modulating vitamins - a new combinatorial therapy prevents cancer cachexia in rat mammary carcinoma. Br J Nutr. 2005;93(6):901–9.
24.
Henriques BJ, Lucas TG, Gomes CM. Therapeutic approaches using riboflavin in mitochondrial energy metabolism disorders. Curr Drug Targets. 2016;17(13):1527–34.PubMed
25.
Ozsvari B, Bonuccelli G, Sanchez-Alvarez R, Foster R, Sotgia F, Lisanti MP. Targeting flavin-containing enzymes eliminates cancer stem cells (CSCs), by inhibiting mitochondrial respiration: vitamin B2 (riboflavin) in cancer therapy. Aging-US. 2017;9(12):2610–28.
26.
Long L, He JZ, Chen Y, Xu XE, Liao LD, Xie YM, Li EM, Xu LY. Riboflavin depletion promotes tumorigenesis in HEK293T and NIH3T3 cells by sustaining cell proliferation and regulating cell cycle-related gene transcription. J Nutr. 2018;148(6):834–43.PubMed
27.
Khan NA, Teli MA, Mohib-ul Haq M, Bhat GM, Lone MM, Afroz F. A survey of risk factors in carcinoma esophagus in the valley of Kashmir, Northern India. J Canc Res Ther. 2011;7(1):15–8.
28.
Zou XN, Taylor PR, Mark SD, Chao A, Wang W, Dawsey SM, Wu YP, Qiao YL, Zheng SF. Seasonal variation of food consumption and selected nutrient intake,in Linxian, a high risk area for esophageal cancer in China. Int J Vitam Nutr Res. 2002;72(6):375–82.PubMed
29.
Siassi F, Ghadirian P. Riboflavin deficiency and esophageal cancer: a case control-household study in the Caspian Littoral of Iran. Cancer Detect Prev. 2005;29(5):464–9.PubMed
30.
Michelhaugh SK, Muzik O, Guastella AR, Klinger NV, Polin LA, Cai H, Xin Y, Mangner TJ, Zhang S, Juha C. Assessment of tryptophan uptake and kinetics using 1-(2-F-18-Fluoroethyl)-L-tryptophan and alpha-C-11-methyl-L-tryptophan PET imaging in mice implanted with patient-derived brain tumor Xenografts. J Nucl Med. 2017;58(2):208–13.
31.
Jasbi P, Wang DF, Cheng SL, Fei Q, Cui JY, Liu L, Wei YP, Raftery D, Gu HW. Breast cancer detection using targeted plasma metabolomics. J Chromatogr B. 2019;1105:26–37.
32.
Bartsch C, Bartsch H. Melatonin in cancer patients and in tumor-bearing animals. Adv Exp Med Biol. 1999;467:247–64.PubMed
33.
Juhasz C, Nahleh Z, Zitron I, Chugani DC, Janabi MZ, Bandyopadhyay S, Ali-Fehmi R, Mangner TJ, Chakraborty PK, Mittal S, et al. Tryptophan metabolism in breast cancers: molecular imaging and immunohistochemistry studies. Nucl Med Biol. 2012;39(7):926–32.PubMedPubMedCentral
34.
Pai V, Marshall A, Hernandez L, Horseman N. Abstract #3365: serotonin a novel marker for breast cancer: bimodal association with breast cancer progression. Cancer Res. 2009;69(9 Supplement):3365.
35.
Leoncikas V, Wu HH, Ward LT, Kierzek AM, Plant NJ. Generation of 2,000 breast cancer metabolic landscapes reveals a poor prognosis group with active serotonin production. Sci Rep. 2016;6:13.
36.
El-Sokkary GH, Ismail IA, Saber SH. Melatonin inhibits breast cancer cell invasion through modulating DJ-1/KLF17/ID-1 signaling pathway. J Cell Biochem. 2019;120(3):3945–57.PubMed
37.
Akkiprik M, Peker I, Ozmen T, Amuran GG, Gulluoglu BM, Kaya H, Ozer A. Identification of differentially expressed IGFBP5-related genes in breast Cancer tumor tissues using cDNA microarray experiments. Genes. 2015;6(4):1201–14.PubMedPubMedCentral
38.
Yongjun Z, Xuefan G, Xiaobing Y. Phenylalanine activates the mitochondria-mediated apoptosis through the RhoA/rho-associated kinase pathway in cortical neurons. Eur J Neurosci. 2010;25(5):1341–8.
39.
Ali MR, Wu Y, Han T, Zang X, Xiao H, Tang Y, Wu R, Fernandez FM, El-Sayed MA. Simultaneous Time-dependent Surface Enhanced Raman Spectroscopy, Metabolomics and Proteomics Reveal Cancer Cell Death Mechanisms Associated with Au-Nanorod Photo-thermal Therapy. J Am Chem Soc. 2016;138(47):jacs.6b08787.
40.
Lien EC, Ghisolfi L, Geck RC, Asara JM, Toker A. Oncogenic PI3K promotes methionine dependency in breast cancer cells through the cystine-glutamate antiporter xCT. Sci Signal. 2017;10(510):13.
41.
Balendiran GK, Dabur R, Fraser D. The role of glutathione in cancer. Cell Biochem Funct. 2004;22(6):343–52.PubMed
42.
Liu XY, Fu YM, Meadows GG. Differential effects of specific amino acid restriction on glucose metabolism, reduction/oxidation status and mitochondrial damage in DU145 and PC3 prostate cancer cells. Oncol Lett. 2011;2(2):349–55.PubMedPubMedCentral
43.
Yang LF, Moss T, Mangala LS, Marini J, Zhao HY, Wahlig S, Armaiz-Pena G, Jiang DH, Achreja A, Win J, et al. Metabolic shifts toward glutamine regulate tumor growth, invasion and bioenergetics in ovarian cancer. Mol Syst Biol. 2014;10(5):23.
Metadata
Title
Cell metabolomics to study the function mechanism of Cyperus rotundus L. on triple-negative breast cancer cells
Authors
Shuangshuang Ma
Fukai Wang
Caijuan Zhang
Xinzhao Wang
Xueyong Wang
Zhiyong Yu
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2020
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-020-02981-w

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