Abstract
In the present study, we investigated the in vitro antitumor functions of a synthetic chalcone derivative 4,3′,4′,5′- tetramethoxychalcone (TMOC) in ovarian cancer cells. We found that TMOC inhibited the proliferation and colony formation of cisplatin sensitive cell line A2780 and resistant cell line A2780/CDDP, as well as ovarian cancer cell line SKOV3 in a time- and dose-dependent manner. Treatment of A2780 cells with TMOC resulted in G0/G1 cell cycle arrest through the down-regulation of cyclin D1 and CDK4, and the up-regulation of p16, p21 and p27 proteins. We demonstrated that TMOC might induce cell apoptosis through suppressing Bcl-2 and Bcl-xL, but enhancing the expression of Bax and the cleavage of PARP-1. Treatment of TMOC also reduced the invasion and migration of A2780 cells. Finally, we found that TMOC inhibited the constitutive activation of STAT3 signaling pathway and induced the expression of the tumor suppressor PTEN regardless of the p53 status in cell lines. These data suggest that TMOC may be developed as a potential chemotherapeutic agent to effectively treat certain cancers including ovarian cancer.
Highlights
IntroductionDue to the lack of sensitive and specific methods for early detection, nearly 60–70% of ovarian cancer patients are diagnosed at advanced stages [1,2]
Ovarian cancer is the leading cause of death from gynecologic malignancies in women
TMOC suppresses cell growth We first determined the anti-proliferative effects of TMOC on human ovarian carcinoma cells, including A2780 (p53 wild-type), A2780/CDDP and SKOV3 (p53 null) cells, as well as pre-neoplastic ovarian epithelial T29 cells
Summary
Due to the lack of sensitive and specific methods for early detection, nearly 60–70% of ovarian cancer patients are diagnosed at advanced stages [1,2]. Despite advances in treatment of ovarian cancer, predominantly involving cytoreductive surgery followed by platinum-based chemotherapy, the survival rate of ovarian cancer patients remains very low [3]. The continued development of novel therapeutic agents for ovarian cancer, especially for the platinum resistant cells, is still urgent. Occurring products from various plants are always important in the discovery of new therapeutic agents [6,7]. Chalcone derivatives (molecules containing 1,3-diphenyl2-3propen-1-one groups), one of the major classes of natural products with widespread distribution in spices, tea, beer, fruits and vegetables, display various interesting biological activities including anti-inflammatory, antimicrobial, antioxidant, and anticancer properties [8,9,10]. As a structure mimics of combretastatin A-4(CA-4), 39,49,59-trimethoxychalcone was reported to exhibit antimitotic properties caused by the inhibition of tubulin polymerization [11,12,13,14]
Sign-in/Register to view highlights & summary 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.
