Induction of apoptosis and histone hyperacetylation by diallyl disulfide in prostate cancer cell line PC-3
Arumugam Arunkumar1, Marati Radhakrishnan Vijayababu, Nandagopal Gunadharini
1Department of Endocrinology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, Tamil Nadu 600 113, India.
Abstract:
Prostate cancer is the most invasive and frequently occurred cancer in men. In the initial stages, it is androgen dependent and the androgen ablation therapy is effective at this stage. In the final stages, it becomes androgen-independent and is unresponsive to androgen ablation therapy. At this stage, induction of apoptosis is considered as a better strategy to control cancer. Histone acetylation and deacetylation are involved in transcriptional activation and transcriptional repression, respectively. Diallyl disulfide (DADS) induced histone hyperacetylation can be correlated with the expression of antiproliferative genes. Induction of apoptosis by DADS has been correlated with histone acetylation. In the present study, DADS, oil soluble organosulfur compound of garlic, has been studied for its effect on histone acetylation and induction of apoptosis in prostate cancer cells in vitro. The induction of apoptosis has been demonstrated by annexin V-FITC binding assay. Extent of apoptosis has been assessed measuring the activity of caspase-3. The results have shown that DADS induced apoptosis in prostate cancer cells in a dose dependent manner. At both 25 and 40 microM concentrations, DADS increased the number of both early and late apoptotic cells. Histone hyperacetylation was also observed in DADS treated cells. It is concluded that DADS, induces apoptosis by influencing histone acetylation in prostate cancer cells.
Insights
Diallyl disulfide (DADS), a compound found in garlic, effectively induces apoptosis, or programmed cell death, in prostate cancer cells. This occurs through a mechanism involving histone hyperacetylation, offering a potential new strategy for cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Prostate cancer progresses from androgen-dependent to androgen-independent stages.
- Apoptosis induction is a key strategy for managing advanced prostate cancer.
- Histone acetylation regulates gene expression, influencing cell proliferation and apoptosis.
Purpose of the Study:
- To investigate the effects of Diallyl disulfide (DADS) on histone acetylation and apoptosis in prostate cancer cells.
- To explore DADS as a potential therapeutic agent for androgen-independent prostate cancer.
Main Methods:
- In vitro study using prostate cancer cell lines.
- Annexin V-FITC binding assay to detect apoptosis.
- Caspase-3 activity assay to quantify apoptosis.
- Assessment of histone acetylation levels.
Main Results:
- DADS treatment dose-dependently induced apoptosis in prostate cancer cells.
- Increased numbers of early and late apoptotic cells were observed at 25 and 40 microM DADS.
- DADS treatment led to significant histone hyperacetylation in treated cells.
Conclusions:
- Diallyl disulfide (DADS) effectively induces apoptosis in prostate cancer cells.
- DADS exerts its pro-apoptotic effects by influencing histone acetylation.
- DADS represents a promising therapeutic candidate for prostate cancer treatment.
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