Metformin against Cancer Stem Cells through the Modulation of Energy Metabolism: Special Considerations on Ovarian Cancer

Ovarian cancer is the most lethal gynecologic malignancy among women worldwide and is presumed to result from the presence of ovarian cancer stem cells. To overcome the limitation of current anticancer agents, another anticancer strategy is necessary to effectively target cancer stem cells in ovarian cancer. In many types of malignancies, including ovarian cancer, metformin, one of the most popular antidiabetic drugs, has been demonstrated to exhibit chemopreventive and anticancer efficacy with respect to incidence and overall survival rates. Thus, the metabolic reprogramming of cancer and cancer stem cells driven by genetic alterations during carcinogenesis and cancer progression could be therapeutically targeted. In this review, the potential efficacy and anticancer mechanisms of metformin against ovarian cancer stem cells will be discussed.

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Novel Therapeutic Strategies for Ovarian Cancer Stem Cells

Frontiers in Oncology ◽

10.3389/fonc.2020.00319 ◽

2020 ◽

Vol 10 ◽

Cited By ~ 7

Author(s):

Nastassja Terraneo ◽

Francis Jacob ◽

Anna Dubrovska ◽

Jürgen Grünberg

Keyword(s):

Ovarian Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Therapeutic Strategies ◽

Ovarian Cancer Stem Cells ◽

Novel Therapeutic Strategies ◽

Novel Therapeutic

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265. Ovarian Cancer Stem Cells Are in an Epithelial/Mesenchymal Hybrid State and Have Multipotential Capacity for Differentiation

Molecular Therapy ◽

10.1016/s1525-0016(16)37706-1 ◽

2010 ◽

Vol 18 ◽

pp. S101

Keyword(s):

Ovarian Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Ovarian Cancer Stem Cells ◽

Hybrid State

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Abstract 1011: Disulfiram superior to ALDH1A1 inhibitor analogs in targeting ovarian cancer stem cells

10.1158/1538-7445.am2021-1011 ◽

2021 ◽

Author(s):

Michael Caminear ◽

Brittney Harrington ◽

Christina Annunziata

Keyword(s):

Ovarian Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Ovarian Cancer Stem Cells

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HER2 decreases drug sensitivity of ovarian cancer cells via inducing stem cell-like property in an NFκB-dependent way

Bioscience Reports ◽

10.1042/bsr20180829 ◽

2019 ◽

Vol 39 (3) ◽

Cited By ~ 1

Author(s):

Wenxiang Wang ◽

Yuxia Gao ◽

Jing Hai ◽

Jing Yang ◽

Shufeng Duan

Keyword(s):

Ovarian Cancer ◽

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Cancer Cells ◽

Drug Sensitivity ◽

Ovarian Cancer Cells ◽

Her2 Overexpression ◽

Her2 Positive ◽

Ovarian Cancer Stem Cells

Abstract Increasing evidence shows that cancer stem cells are responsible for drug resistance and relapse of tumors. In breast cancer, human epidermal growth factor receptor 2 (HER2) induces Herceptin resistance by inducing cancer stem cells. In the present study, we explored the effect of HER2 on cancer stem cells induction and drug sensitivity of ovarian cancer cell lines. First, we found that HER2 overexpression (HER2 OE) induced, while HER2 knockdown (HER2 KD) decreased CD44+/CD24− population. Consistently, HER2 expression was closely correlated with the sphere formation efficiency (SFE) of ovarian cancer cells. Second, we found that NFκB inhibition by specific inhibitor JSH23 or siRNA targetting subunit p65 dramatically impaired the induction of ovarian cancer stem cells by HER2, indicating that NFκB mediated HER2-induced ovarian cancer stem cells. Third, we found that HER2 KD significantly attenuated the tumorigenicity of ovarian cancer cells. Further, we found that HER2 inhibition increased drastically the sensitivity of ovarian cancer cells to doxorubicin (DOX) or paclitaxel (PTX). Finally, we examined the correlation between HER2 status and stem cell-related genes expression in human ovarian tumor tissues, and found that expressions of OCT4, COX2, and Nanog were higher in HER2 positive tumors than in HER2 negative tumors. Consistently, the 5-year tumor-free survival rate of HER2 positive patients was dramatically lower than HER2 negative patients. Taken together, our data indicate that HER2 decreases drug sensitivity of ovarian cancer cells via inducing stem cell-like property.

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