Induction of G0/G1 phase cell cycle arrest and apoptosis by thymol through ROS generation and caspase-9/-3 activation in breast and colorectal cancer cell lines
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Published on: May 14, 2016
Riyasdeen Anvarbatcha1, Faisal Kunnathodi, Mozaffarul Islam
1Scientific Research Center, Prince Sultan Military Medical City, Riyadh-11159, Kingdom of Saudi Arabia.
Background:
Cancer is a major malignancy and one of the leading causes of death; it calls for a proactive strategy for the cure. Herbs are reservoirs of novel chemical entities and their phytochemical exploration has contributed considerably to the discovery of new anticancer drugs. Thymol, a natural phenolic monoterpenoid, has been implicated with many medicinal properties, including anticancer ones. However, the anti-proliferative and apoptosis-inducing ability of thymol on MDA-MB-231 and HCT-8 cell lines has not been studied yet in detail, and hence this study was conceived.
Materials And Methods:
We studied the cytotoxicity, morphological alterations of the cell, oxidative stress, cell cycle modulation, apoptosis and expression of apoptosis-related proteins that ensued due to thymol treatment in these cancer cells.
Results:
Thymol inhibited the cell proliferation, altered the morphology of the cells, increased the intracellular ROS level, arrested the cells in G0/G1 phase, induced apoptosis, upregulated pro-apoptotic protein p53 expression, downregulated anti-apoptotic protein Bcl-xL expression, and activated caspase-9 and -3.
Conclusion:
These findings elucidate that thymol induces apoptosis through the intrinsic pathway, in MDA-MB-231 breast and HCT-8 colorectal cancer cells through ROS generation and G0/G1 phase cell cycle arrest. This reiterates the broad-spectrum anti-tumor potential of thymol and provides an insight to study further to be developed into an anticancer drug.
Insights
Thymol, a natural compound, effectively inhibits cancer cell proliferation and induces apoptosis in breast and colorectal cancer cells. It works by generating reactive oxygen species (ROS) and arresting cells in the G0/G1 phase, highlighting its anticancer potential.
Area of Science:
- Phytochemistry
- Molecular Biology
- Cancer Research
Background:
- Herbal compounds are a rich source of novel anticancer agents.
- Thymol, a natural monoterpenoid, exhibits various medicinal properties, including anticancer effects.
- Limited studies exist on thymol's specific anti-proliferative and apoptosis-inducing effects on MDA-MB-231 and HCT-8 cancer cell lines.
Purpose of the Study:
- To investigate the anti-proliferative and apoptosis-inducing effects of thymol on MDA-MB-231 (breast) and HCT-8 (colorectal) cancer cell lines.
- To elucidate the underlying mechanisms of thymol-induced cancer cell death.
Main Methods:
- Cytotoxicity assays to assess cell viability.
- Morphological analysis to observe cellular changes.
- Measurement of intracellular reactive oxygen species (ROS) levels.
- Cell cycle analysis to determine cell cycle phase distribution.
- Apoptosis assays and Western blotting to analyze apoptosis-related protein expression and caspase activation.
Main Results:
- Thymol significantly inhibited cell proliferation and induced morphological changes in cancer cells.
- Treatment with thymol led to increased intracellular ROS levels.
- Thymol caused cell cycle arrest at the G0/G1 phase.
- Apoptosis was induced, evidenced by upregulated p53, downregulated Bcl-xL, and activated caspase-9 and -3.
Conclusions:
- Thymol induces apoptosis in MDA-MB-231 and HCT-8 cancer cells via the intrinsic pathway.
- ROS generation and G0/G1 cell cycle arrest are key mechanisms in thymol-induced apoptosis.
- These findings support thymol's broad-spectrum antitumor potential and suggest its further development as an anticancer therapeutic.
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