Genistein-inhibited Cancer Stem Cell-like Properties and Reduced Chemoresistance of Gastric Cancer

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2014 Feb 28

PMID 24573253

Citations 44

Authors

Weifeng Huang

Chunpeng Wan

Qicong Luo

Zhengjie Huang

Qi Luo

Affiliations

Soon will be listed here.

Abstract

Genistein, the predominant isoflavone found in soy products, has exerted its anticarcinogenic effect in many different tumor types in vitro and in vivo. Accumulating evidence in recent years has strongly indicated the existence of cancer stem cells in gastric cancer. Here, we showed that low doses of genistein (15 µM), extracted from Millettia nitida Benth var hirsutissima Z Wei, inhibit tumor cell self-renewal in two types of gastric cancer cells by colony formation assay and tumor sphere formation assay. Treatment of gastric cancer cells with genistein reduced its chemoresistance to 5-Fu (fluorouracil) and ciplatin. Further results indicated that the reduced chemoresistance may be associated with the inhibition of ABCG2 expression and ERK 1/2 activity. Furthermore, genistein reduced tumor mass in the xenograft model. Together, genistein inhibited gastric cancer stem cell-like properties and reduced its chemoresistance. Our results provide a further rationale and experimental basis for using the genistein to improve treatment of patients with gastric cancer.

Citing Articles

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Articulating the Pharmacological and Nanotechnological Aspects of Genistein: Current and Future Prospectives.

Bansal K, Singh V, Mishra S, Bajpai M Curr Pharm Biotechnol. 2024; 25(7):807-824.

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References

Huang W, Liu H, Wang T, Zhang T, Kuang J, Luo Y . Tonicity-responsive microRNAs contribute to the maximal induction of osmoregulatory transcription factor OREBP in response to high-NaCl hypertonicity. Nucleic Acids Res. 2010; 39(2):475-85. PMC: 3025551. DOI: 10.1093/nar/gkq818. View

Kaufman P, Duke J, Brielmann H, Boik J, Hoyt J . A comparative survey of leguminous plants as sources of the isoflavones, genistein and daidzein: implications for human nutrition and health. J Altern Complement Med. 1997; 3(1):7-12. DOI: 10.1089/acm.1997.3.7. View

Peterson G, Barnes S . Genistein inhibits both estrogen and growth factor-stimulated proliferation of human breast cancer cells. Cell Growth Differ. 1996; 7(10):1345-51. View

Matsukawa Y, Marui N, Sakai T, Satomi Y, Yoshida M, Matsumoto K . Genistein arrests cell cycle progression at G2-M. Cancer Res. 1993; 53(6):1328-31. View

Takaishi S, Okumura T, Wang T . Gastric cancer stem cells. J Clin Oncol. 2008; 26(17):2876-82. PMC: 2743304. DOI: 10.1200/JCO.2007.15.2603. View

Banerjee S, Li Y, Wang Z, Sarkar F . Multi-targeted therapy of cancer by genistein. Cancer Lett. 2008; 269(2):226-42. PMC: 2575691. DOI: 10.1016/j.canlet.2008.03.052. View

Liu J, Ma L, Xu J, Liu C, Zhang J, Liu J . Co-expression of CD44 and ABCG2 in spheroid body-forming cells of gastric cancer cell line MKN45. Hepatogastroenterology. 2013; 60(125):975-80. DOI: 10.5754/hge121189. View

Farina H, Pomies M, Alonso D, Gomez D . Antitumor and antiangiogenic activity of soy isoflavone genistein in mouse models of melanoma and breast cancer. Oncol Rep. 2006; 16(4):885-91. View

Yuasa Y . Control of gut differentiation and intestinal-type gastric carcinogenesis. Nat Rev Cancer. 2003; 3(8):592-600. DOI: 10.1038/nrc1141. View

10.

Takaishi S, Okumura T, Tu S, Wang S, Shibata W, Vigneshwaran R . Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells. 2009; 27(5):1006-20. PMC: 2746367. DOI: 10.1002/stem.30. View

11.

Vidal S, Rodriguez-Bravo V, Galsky M, Cordon-Cardo C, Domingo-Domenech J . Targeting cancer stem cells to suppress acquired chemotherapy resistance. Oncogene. 2013; 33(36):4451-63. DOI: 10.1038/onc.2013.411. View

12.

Yang L, Ping Y, Yu X, Qian F, Guo Z, Qian C . Gastric cancer stem-like cells possess higher capability of invasion and metastasis in association with a mesenchymal transition phenotype. Cancer Lett. 2011; 310(1):46-52. DOI: 10.1016/j.canlet.2011.06.003. View

13.

Kim E, Kwon K, Song M, Seo S, Park S, Ka S . Genistein protects pancreatic beta cells against cytokine-mediated toxicity. Mol Cell Endocrinol. 2007; 278(1-2):18-28. DOI: 10.1016/j.mce.2007.08.003. View

14.

Jiang J, Chuai S, Wang Z, Zheng D, Xu F, Zhang Y . Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90 phenotype. Oncogene. 2011; 31(6):671-82. DOI: 10.1038/onc.2011.282. View

15.

Sarkar F, Adsule S, Padhye S, Kulkarni S, Li Y . The role of genistein and synthetic derivatives of isoflavone in cancer prevention and therapy. Mini Rev Med Chem. 2006; 6(4):401-7. DOI: 10.2174/138955706776361439. View

16.

Clarke M, Dick J, Dirks P, Eaves C, Jamieson C, Jones D . Cancer stem cells--perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res. 2006; 66(19):9339-44. DOI: 10.1158/0008-5472.CAN-06-3126. View

17.

Nishii T, Yashiro M, Shinto O, Sawada T, Ohira M, Hirakawa K . Cancer stem cell-like SP cells have a high adhesion ability to the peritoneum in gastric carcinoma. Cancer Sci. 2009; 100(8):1397-402. PMC: 11159778. DOI: 10.1111/j.1349-7006.2009.01211.x. View

18.

Chen T, Yang K, Yu J, Meng W, Yuan D, Bi F . Identification and expansion of cancer stem cells in tumor tissues and peripheral blood derived from gastric adenocarcinoma patients. Cell Res. 2011; 22(1):248-58. PMC: 3351913. DOI: 10.1038/cr.2011.109. View

19.

Ramirez A, Garcia-Rubio S . Current progress in the chemistry and pharmacology of akuammiline alkaloids. Curr Med Chem. 2003; 10(18):1891-915. DOI: 10.2174/0929867033457016. View

20.

Zhang C, Li C, He F, Cai Y, Yang H . Identification of CD44+CD24+ gastric cancer stem cells. J Cancer Res Clin Oncol. 2011; 137(11):1679-86. DOI: 10.1007/s00432-011-1038-5. View