Monascin accelerates anoikis in circulating tumor cells and prevents breast cancer metastasis

Chen,Kung‑Yen; Lin,Jui-An; Yao,Han-Yun; Hsu,An-Chih; Tai,Yu‑Ting; Ho,Bing‑Ying

doi:10.3892/ol.2020.12029

Monascin accelerates anoikis in circulating tumor cells and prevents breast cancer metastasis

Authors:
- Kung‑Yen Chen
- Jui-An Lin
- Han-Yun Yao
- An-Chih Hsu
- Yu‑Ting Tai
- Bing‑Ying Ho
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Affiliations: Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan, Department of General Surgery, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
Published online on: August 27, 2020 https://doi.org/10.3892/ol.2020.12029
Article Number: 166
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Anoikis resistance has been observed in various types of cancers in which anchorage‑independent growth is a crucial step for cancer metastasis. Therefore, agents interfering with this specific cancer cell behavior may be integrated into novel antimetastatic strategies. Monascin (MS), a secondary metabolite found in Monascus species, is a known potent chemopreventive compound used for treating metabolic complications; however, the effect of MS on anoikis resistance has not been investigated. In this study, 4T1 breast cells were treated with MS under either suspension or adhesion conditions. The higher cytotoxicity of MS was more potent against suspended cells than against adherent cells. This selective cytotoxicity was due to the induction of anoikis, which was evidenced by changes in cell aggregation, caspase activity, and Annexin V/propidium iodide binding as well as the results of systemic metastasis in an animal model. Furthermore, MS inhibited E‑cadherin and β‑catenin expression in the cells; the treated cells formed spherical aggregates, which suggested that anchorage‑independent growth was prevented by MS. These results provide new insights into the mechanisms underlying the growth‑preventing effect of MS on cancer cells and indicate the potential ability of MS to suppress metastasis.

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1	Aceto N, Bardia A, Miyamoto DT, Donaldson MC, Wittner BS, Spencer JA, Yu M, Pely A, Engstrom A, Zhu H, et al: Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell. 158:1110–1122. 2014. View Article : Google Scholar : PubMed/NCBI
2	Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW and Hayes DF: Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 351:781–791. 2004. View Article : Google Scholar : PubMed/NCBI
3	van Dalum G, Holland L and Terstappen LW: Metastasis and circulating tumor cells. EJIFCC. 23:87–97. 2012.PubMed/NCBI
4	Sirimangkalakitti N, Chamni S, Suwanborirux K and Chanvorachote P: Renieramycin M Sensitizes Anoikis-resistant H460 lung cancer cells to anoikis. Anticancer Res. 36:1665–1671. 2016.PubMed/NCBI
5	Zhang X, Yang L, Chien S and Lv Y: Suspension state promotes metastasis of breast cancer cells by up-regulating cyclooxygenase-2. Theranostics. 8:3722–3736. 2018. View Article : Google Scholar : PubMed/NCBI
6	Zou G, Ren B, Liu Y, Fu Y, Chen P, Li X, Luo S, He J, Gao G, Zeng Z, et al: Inhibin B suppresses anoikis resistance and migration through the transforming growth factor-β signaling pathway in nasopharyngeal carcinoma. Cancer Sci. 109:3416–3427. 2018. View Article : Google Scholar : PubMed/NCBI
7	Cominetti MR, Altei WF and Selistre-de-Araujo HS: Metastasis inhibition in breast cancer by targeting cancer cell extravasation. Breast Cancer (Dove Med Press). 11:165–178. 2019.PubMed/NCBI
8	Laguinge LM, Samara RN, Wang W, El-Deiry WS, Corner G, Augenlicht L, Mishra L and Jessup JM: DR5 receptor mediates anoikis in human colorectal carcinoma cell lines. Cancer Res. 68:909–917. 2008. View Article : Google Scholar : PubMed/NCBI
9	Steadman K, Stein WD, Litman T, Yang SX, Abu-Asab M, Dutcher SK and Bates S: PolyHEMA spheroids are an inadequate model for the drug resistance of the intractable solid tumors. Cell Cycle. 7:818–829. 2008. View Article : Google Scholar : PubMed/NCBI
10	Hong Y, Fang F and Zhang Q: Circulating tumor cell clusters: What we know and what we expect (Review). Int J Oncol. 49:2206–2216. 2016. View Article : Google Scholar : PubMed/NCBI
11	Kang HG, Jenabi JM, Zhang J, Keshelava N, Shimada H, May WA, Ng T, Reynolds CP, Triche TJ and Sorensen PH: E-cadherin cell-cell adhesion in ewing tumor cells mediates suppression of anoikis through activation of the ErbB4 tyrosine kinase. Cancer Res. 67:3094–3105. 2007. View Article : Google Scholar : PubMed/NCBI
12	Giannoni E, Fiaschi T, Ramponi G and Chiarugi P: Redox regulation of anoikis resistance of metastatic prostate cancer cells: Key role for Src and EGFR-mediated pro-survival signals. Oncogene. 28:2074–2086. 2009. View Article : Google Scholar : PubMed/NCBI
13	Lee BH, Hsu WH, Huang T, Chang YY, Hsu YW and Pan TM: Effects of monascin on anti-inflammation mediated by Nrf2 activation in advanced glycation end product-treated THP-1 monocytes and methylglyoxal-treated wistar rats. J Agric Food Chem. 61:1288–1298. 2013. View Article : Google Scholar : PubMed/NCBI
14	Su NW, Lin YL, Lee MH and Ho CY: Ankaflavin from Monascus-fermented red rice exhibits selective cytotoxic effect and induces cell death on Hep G2 cells. J Agric Food Chem. 53:1949–1954. 2005. View Article : Google Scholar : PubMed/NCBI
15	Ho BY, Lin CH, Apaya MK, Chao WW and Shyur LF: Silibinin and paclitaxel cotreatment significantly suppress the activity and lung metastasis of triple negative 4T1 mammary tumor cell in mice. J Tradit Complement Med. 2:301–311. 2012. View Article : Google Scholar : PubMed/NCBI
16	Mohamed MS, Bishr MK, Almutairi FM and Ali AG: Inhibitors of apoptosis: Clinical implications in cancer. Apoptosis. 22:1487–1509. 2017. View Article : Google Scholar : PubMed/NCBI
17	Kim YN, Koo KH, Sung JY, Yun UJ and Kim H: Anoikis resistance: An essential prerequisite for tumor metastasis. Int J Cell Biol. 2012:3068792012. View Article : Google Scholar : PubMed/NCBI
18	Piyush T, Rhodes JM and Yu LG: MUC1 O-glycosylation contributes to anoikis resistance in epithelial cancer cells. Cell Death Discov. 3:170442017. View Article : Google Scholar : PubMed/NCBI
19	Tien YW, Kuo HC, Ho BI, Chang MC, Chang YT, Cheng MF, Chen HL, Liang TY, Wang CF, Huang CY, et al: A high circulating tumor cell count in portal vein predicts liver metastasis from periampullary or pancreatic cancer: A high portal venous CTC count predicts liver metastases. Medicine (Baltimore). 95:e34072016. View Article : Google Scholar : PubMed/NCBI
20	Park JY, Jeong AL, Joo HJ, Han S, Kim SH, Kim HY, Lim JS, Lee MS, Choi HK and Yang Y: Development of suspension cell culture model to mimic circulating tumor cells. Oncotarget. 9:622–640. 2018. View Article : Google Scholar : PubMed/NCBI
21	Cheng CF and Pan TM: Monascus-fermented red mold dioscorea protects mice against alcohol-induced liver injury, whereas its metabolites ankaflavin and monascin regulate ethanol-induced peroxisome proliferator-activated receptor-gamma and sterol regulatory element-binding transcription factor-1 expression in HepG2 cells. J Sci Food Agric. 98:1889–1898. 2018. View Article : Google Scholar : PubMed/NCBI
22	Khanna C and Hunter K: Modeling metastasis in vivo. Carcinogenesis. 26:513–523. 2005. View Article : Google Scholar : PubMed/NCBI
23	Bill R and Christofori G: The relevance of EMT in breast cancer metastasis: Correlation or causality? FEBS Lett. 589:1577–1587. 2015. View Article : Google Scholar : PubMed/NCBI
24	Alix-Panabieres C, Mader S and Pantel K: Epithelial-mesenchymal plasticity in circulating tumor cells. J Mol Med (Berl). 95:133–142. 2017. View Article : Google Scholar : PubMed/NCBI
25	Melzer C, von der Ohe J and Hass R: Breast carcinoma: From initial tumor cell detachment to settlement at secondary sites. Biomed Res Int. 2017:85343712017. View Article : Google Scholar : PubMed/NCBI
26	Gao C, Xiao G and Hu J: Regulation of Wnt/β-catenin signaling by posttranslational modifications. Cell Biosci. 4:132014. View Article : Google Scholar : PubMed/NCBI
27	Green SK, Francia G, Isidoro C and Kerbel RS: Antiadhesive antibodies targeting E-cadherin sensitize multicellular tumor spheroids to chemotherapy in vitro. Mol Cancer Ther. 3:149–159. 2004.PubMed/NCBI