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The apoptotic mechanisms of MT-6, a mitotic arrest inducer, in human ovarian cancer cells.


ABSTRACT: Patients with ovarian cancer are typically diagnosed at an advanced stage, resulting in poor prognosis since there are currently no effective early-detection screening tests for women at average-risk for ovarian cancer. Here, we investigated the effects of MT-6, a derivative of moscatilin, in ovarian cancer cells. Our investigation showed that MT-6 inhibited the proliferation and viability of ovarian cancer cells with submicromolar IC50 values. MT-6-treated SKOV3 cells showed significant cell cycle arrest at G2/M phase, followed by an increase in the proportion of cells in a sub-G1 phase. In addition, MT-6 induced a concentration-dependent increase in mitotic markers, mitotic kinases, cell cycle regulators of G2/M transition, and apoptosis-related markers in ovarian cancer cells. MT-6 treatment also induced mitochondrial membrane potential loss, JNK activation, and DR5 expression. Cotreatment of cells with the JNK inhibitor SP600125 considerably attenuated MT-6-induced apoptosis, mitochondria membrane potential loss, DR5 upregulation, and suppression of cell viability. MT-6 also inhibited tumor growth in an SKOV3 xenograft model without significant body weight loss. Together, our findings suggest that MT-6 is a potent anticancer agent with tumor-suppressive activity in vitro and in vivo that could be further investigated for ovarian cancer therapy in the future.

SUBMITTER: Chen MC 

PROVIDER: S-EPMC5384015 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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The apoptotic mechanisms of MT-6, a mitotic arrest inducer, in human ovarian cancer cells.

Chen Mei-Chuan MC   Kuo Yi-Chiu YC   Hsu Chia-Ming CM   Chen Yi-Lin YL   Shen Chien-Chang CC   Teng Che-Ming CM   Pan Shiow-Lin SL  

Scientific reports 20170407


Patients with ovarian cancer are typically diagnosed at an advanced stage, resulting in poor prognosis since there are currently no effective early-detection screening tests for women at average-risk for ovarian cancer. Here, we investigated the effects of MT-6, a derivative of moscatilin, in ovarian cancer cells. Our investigation showed that MT-6 inhibited the proliferation and viability of ovarian cancer cells with submicromolar IC<sub>50</sub> values. MT-6-treated SKOV3 cells showed signific  ...[more]

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