Abstract
Carcinogenesis is predominantly dependent on the cancer stem cells (CSCs) residing or populating within the cancer. We previously demonstrated that the novel synthetic genistein analogue, 7-difluoromethoxyl-5,4'-di-n-octylgenistein (DFOG), induced apoptotic cell death of ovarian and gastric cancer cells. The present study demonstrated that sphere‑forming cells (SFCs) derived from the ovarian cancer cell-line SKOV3 possessed ovarian cancer stem-like cell (OCSLC) properties, including self-renewal and high tumorigenicity. DFOG may be effective in inhibiting the self‑renewal capacity of SFCs derived from the SKOV3 cell line. DFOG decreased the level of phosphorylated FOXO3a protein in SKOV3 cell‑derived SFCs. The inhibition of FOXO3a expression by siRNA significantly attenuated the ability of DFOG to inhibit the self-renewal capacity of SKOV3-derived SFCs. Our results suggested that DFOG has been demonstrated to significantly inhibit the self-renewal capacity of ovarian cancer stem cells (OCSCs) through a mechanism partly dependent on the activation of FOXO3a.
Highlights
Ovarian cancer is the fourth leading cause of cancer‐related mortality in females in the world and the leading cause of mortality from a gynecological cancer
The current study demonstrated that sphere-forming cells (SFCs) derived from the ovarian cancer cell-line SKOV3 possessed ovarian cancer stem-like cell (OCSLC) properties, including self-renewal and high tumorigenicity
To determine if a population of self-renewing cancer stem cells (CSCs) exists in ovarian cell-lines, SKOV3, OVCAR-3 and A2780 ovarian cancer cell‐lines were grown in serum-free sphere‐forming conditions
Summary
Ovarian cancer is the fourth leading cause of cancer‐related mortality in females in the world and the leading cause of mortality from a gynecological cancer. The standard first‐line treatment for ovarian cancer has not markedly altered since 1996 and includes the intravenous administration of a platinum agent. Cancer progression and development is predominantly dependent on the cancer stem cells (CSCs) residing or populating within the cancer. The self-renewing, near infinite proliferative capacity and potential for differentiation of CSCs is of vital importance in the occurrence, development and metastasis of cancer. It is believed that targeting CSCs may offer important and perhaps revolutionary advances in the targeting of cancer. Studies by our laboratory have demonstrated that the novel synthetic genistein analogue, 7-difluoromethoxyl-5,4'-di-n-octyl genistein (DFOG), induced cellular apoptotic death of ovarian and gastric cancer cells [17,18]. Whether DFOG inhibits the selfrenewing capacity of ovarian cancer stem cells (OCSCs) has not been previously demonstrated
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