Abstract
Ovarian cancer is the fifth leading cause of deaths due to cancer among women in the United States. In 2017, 22,440 women are expected to be diagnosed with ovarian cancer and 14,080 women will die with it. Currently used chemotherapies (Cisplatin or platinum/taxane combination) targets cancer cells, but spares cancer stem cells (CSCs), which are responsible for tumor relapse leading to recurrence of cancer. Aldehyde dehydrogenase I (ALDH1) positive cancer stem cells are one of the major populations in ovarian tumor and have been related to tumor progression and metastasis. In our studies, we observed expression of ALDH1 in both ovarian surface epithelium (OSE) and cortex with high levels of expression in OSE in normal ovary and benign (BN) tumor, compared to borderline (BL) and high grade (HG) ovarian tumors. In contrast, high levels of expression of ALDH1 were observed in cortex in BL and HG tumors compared to normal ovary and BN tumor. Withaferin A (WFA) alone or in combination with cisplatin (CIS) significantly inhibited the spheroid formation (tumorigenic potential) of isolated ALDH1 CSCs in vitro and significantly reduced its expression in tumors collected from mice bearing orthotopic ovarian tumor compared to control. Treatment of animals with CIS alone significantly increased the ALDH1 CSC population in tumors, suggesting that CIS targets cancer cells but spares cancer stem cells, which undergo amplification. WFA and CIS combination suppresses the expression of securin an “oncogene”, suggesting that securin may serve as a downstream signaling gene to mediate the antitumor effects of WFA.
Highlights
Ovarian cancer is the most lethal of all the gynecological malignancies, affecting over 22,000 women annually in the United States alone [1]
In our recent studies [25], we showed a significant increase in CD24, CD34, CD44, CD117, and Oct4 positive cancer stem cells in tumors collected from mice bearing implanted orthotopic ovarian cancer followed by treatment with CIS
Expression of Aldehyde dehydrogenase 1 (ALDH1) appeared to be higher in ovarian surface epithelium (OSE) in normal ovary and BN tumor compared to BL and high grade (HG) tumors
Summary
Ovarian cancer is the most lethal of all the gynecological malignancies, affecting over 22,000 women annually in the United States alone [1]. In our recent studies [25], we showed a significant increase in CD24, CD34, CD44, CD117, and Oct positive cancer stem cells in tumors collected from mice bearing implanted orthotopic ovarian cancer followed by treatment with CIS. These results strongly suggest that CIS or its derivatives, which are commonly used as first line chemotherapy for various cancers, kill cancer cells, spare CSCs that undergo amplification and lead to recurrence of cancer. It has been purported to possess anticancer, anti-inflammatory, antiangiogenic and cardio-protective effects [26,27,28,29,30,31]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
