Diallyl disulfide (DADS) induced apoptosis undergo caspase-3 activity in human bladder cancer T24 cells
1Department of Clinical Pathology, Cheng-Hsin Rehabilitation Medical Center, Taipei 100, Taiwan, ROC.
Abstract:
Diallyl disulfide (DADS), one of the major components of garlic (Allium sativum), is well known to have chemopreventative activity against human cancer such as colon, lung and skin. But the exact mechanism of the action is still unclear. In this study, we investigated how DADS--induced cell cycle arrest and apoptosis in T24 human bladder cancer cells in vitro. Apoptosis induction, cell viability, cell cycle arrest, caspases-3, -9 activity and gene expression were measured to determine their variation by flow cytometric assay, western blot, and determination of caspase-3 activity, PCR and cDNA microarray. There are significant differences in cell death (decreased viable cells then increased the amounts of apoptosis) of T24 cells that were detected between DADS (5-75 microM) treated and untreated groups. A significant increase was found in apoptosis induction when cells were treated with DADS (50 microM) compared to without DADS treated groups. DADS also promoted caspase-3 activity after exposure for 1, 3, 6, 12, and 24 h, which led to induce apoptosis. DADS also increased the product of intracellular hydrogen peroxide. Furthermore, the DADS-induced apoptosis on T24 cells was blocked by the broad-spectrum caspase inhibitor, z-VAD-fmk and antioxidant (catalase). DADS also increased cyclin E and decreased CDK2 gene expression which may lead to the G2/M arrest of T24 cells.
Insights
Diallyl disulfide (DADS), a garlic compound, induces apoptosis and cell cycle arrest in human bladder cancer cells. This mechanism involves caspase activation and altered gene expression, suggesting DADS
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Diallyl disulfide (DADS), a key component of garlic (Allium sativum), exhibits known chemopreventative properties against various human cancers.
- The precise molecular mechanisms underlying DADS's anti-cancer effects remain incompletely understood.
Purpose of the Study:
- To elucidate the mechanisms by which DADS induces cell cycle arrest and apoptosis in T24 human bladder cancer cells in vitro.
- To investigate the role of caspases and gene expression in DADS-mediated anti-cancer activity.
Main Methods:
- Flow cytometry was used to assess apoptosis induction and cell cycle arrest.
- Western blot analysis and caspase-3 activity assays quantified protein expression and enzyme activity.
- Polymerase chain reaction (PCR) and cDNA microarray identified changes in gene expression.
Main Results:
- DADS treatment (5-75 microM) significantly increased apoptosis and decreased viable T24 cells.
- DADS (50 microM) markedly enhanced apoptosis induction and caspase-3 activity over 24 hours.
- DADS increased intracellular hydrogen peroxide, and its effects were reversed by caspase inhibitors and catalase.
- DADS altered gene expression, increasing cyclin E and decreasing CDK2, potentially causing G2/M arrest.
Conclusions:
- DADS effectively induces apoptosis and cell cycle arrest in T24 human bladder cancer cells.
- The pro-apoptotic effects of DADS are mediated through caspase activation and are influenced by reactive oxygen species.
- DADS modulates key cell cycle regulatory genes, contributing to its anti-cancer potential.
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