Anticancer effects of a novel chroman analog in HeLa cells are associated with G2-phase arrest and mitochondrial-mediated apoptosis

作者：Jeong Hyunjin; Shin Yumi; Kim Dong Kyoo^*

来源：Oncology Reports, 2018, 40(1): 545-553.

DOI：10.3892/or.2018.6404

• chroman analogs
• cell cycle
• apoptosis
• reactive oxygen species

In the present study, the anticancer activity of 1-[(3S,4R)-2,2-dimethyl-3-oxo-4-(2-piperidonyl)chroman-6-yl]-3-phenylurea (S32) was investigated by testing its effect in vitro on the growth of HeLa cells. First, we showed that the IC50 value of S32 was similar to 70 mu M by using WST-8 assay, and that it significantly inhibited the proliferation and viability of HeLa cells in a dose-dependent manner after 48 h. Morphological changes in apoptotic cells included cellular shrinkage and nuclear condensation. The results of [H-3]-thymidine incorporation and flow cytometric analysis indicated that S32 induced inhibition of DNA replication and G2-phase cell cycle arrest. Moreover, S32 induced the levels of reactive oxygen species (ROS) and decreased the mitochondrial membrane potential (MMP) in a time-dependent manner. Using Annexin V-FITC/propidium iodide (PI) dual staining assay, we found that S32 noticeably increased early apoptosis in HeLa cells in a time-dependent manner. The result of western blot analysis showed that the apoptotic induction was associated with an increase in Bax levels and a decrease in Bcl-2 levels, which led to activation of caspase-8, -9 and -3. Taken together, our findings demonstrated that S32 induces mitochondrial-mediated apoptosis in HeLa cells and suggest that S32 has potential as an anticancer drug.

• 出版日期2018-7