Abstract
Ovarian cancer is the fifth leading cause of cancer-related deaths in women. Despite treatment, most patients experience relapse and the 5-year survival rate of ovarian cancer is less than 50%. Serotonin has cell growth-promoting functions in a variety of carcinomas, but the effect of serotonin receptor antagonists on ovarian cancer cells is unknown. In this study, it was confirmed that methiothepin, a serotonin receptor antagonist, suppresses the viability of, and induces apoptosis in, ovarian cancer cells. Methiothepin also induces mitochondrial dysfunction, represented by depolarization of the mitochondrial membrane and increased mitochondrion-specific Ca2+ levels, and causes metabolic disruption in cancer cells such as decreased ATP production and oxidative phosphorylation. Methiothepin also interferes with vascular development in transgenic zebrafish embryos. Combination treatment with methiothepin improves the anti-cancer effect of paclitaxel, a standard chemotherapeutic agent. In conclusion, this study revealed that methiothepin is a potential novel therapeutic agent for ovarian cancer treatment.
Highlights
Ovarian cancer is the second most frequent and most lethal gynecological malignancy [1]
We investigated whether methiothepin could induce mitochondrial disruption and metabolic imbalances in ovarian cancer cells
After analyzing the change in the viability of ovarian cancer cells in response to methiothepin, it was confirmed that the cell viability was significantly reduced in a dose- and time-dependent manner (Figure 1A)
Summary
Ovarian cancer is the second most frequent and most lethal gynecological malignancy [1]. G protein coupled receptor (GPCR)-dependent Ca2+ signaling is reported to be activated by many types of neurotransmitters [5]. Serotonin has a mitogenic effect in ovarian cancer cells [9]. There is some evidence that regulation of serotonin activity can inhibit the progression or increase the drug sensitivity of ovarian cancer, but little is known about how serotonin antagonists affect ovarian cancer cells. This study evaluated alterations in the proliferation and viability of the ovarian cancer cell lines ES2 and OV90 in response to methiothepin treatment. The synergistic anti-cancer effect of methiothepin on ovarian cancer cells was verified through combination treatment with paclitaxel, a standard drug in chemotherapeutic approaches for the treatment of ovarian cancer
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.
