Liver cancer is the most common form of cancer in Taiwan and it usually responds to chemotherapy. However, patients often have side effects to the chemotherapeutic drugs. Thus new agents are urgently required to treat liver cancer. Chrysophanol, one of the anthraquinone derivatives, was reported to inhibit some human cancer cell growth which may be due to the induction of apoptosis similar to other anthraquinone derivatives though such actions have not been reported. In the present study, we reported that chrysophanol inhibits cell growth in Hep3B liver cancer cells based on the following observations: 1) induc cell morphological changes; 2) decreased percentage of viable cells; 3) induced S phase arrest of cell cycle progression; 4) induced DNA damage as measured by comet assay and DAPI staining. Chrysophanol-induced cell death however, seems to be related to necrotic processes rather than typical apoptosis. Chrysophanol induced reactive oxygen species and Ca(2+) production and decreased mitochondrial membrane potential (ΔΨm) and ATP levels in Hep3B cells. No effects were observed on known protein regulators of apoptosis such as Bax and Bcl-2. Chrysophanol-induced cell death took place independently of caspase-8 and -9. Based on our findings, we propose that chrysophanol reduces cellular ATP levels causing a drop in energy resulting in necrotic-like cell death.
Diallyl sulfide (DAS) is a component of garlic (Alliaceae family). Although diallyl polysulfide has been shown to exhibit anticancer activities, no report explored DAS-affected cell death in human cervical cancer cells in vitro. This study investigated DAS affected on cell-cycle regulation and apoptosis in human cervical cancer Ca Ski cells. DAS at 25-100 μM decreased the viability of Ca Ski cells by increasing G0/G1 phase arrest followed by induction of apoptosis in concentration- and time-dependent effects. Flow cytomteric assay indicated that DAS (75 μM) promoted the production of Ca(2+) accumulation and decreased the level of mitochondrial membrane potential in Ca Ski cells. Western blotting showed that 75 μM of DAS-induced G0/G1 phase arrest was mediated through the increased expression of p21, p27, and p53 with a simultaneous decrease in CDK2, CDK6, and CHK2 expression. The characteristics of apoptosis, such as morphological changes and DNA condensation, altered the ratio of Bax/Bcl-2 and sub-G1 phase occurred in Ca Ski cells after exposure to DAS. Furthermore, DAS induced mitochondrial dysfunction, leading to the release of cytochrome c for causing apoptosis in Ca Ski cells. These findings suggest that DAS might be a potential chemotherapeutic agent for the treatment of cervical cancer.
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