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Published on: June 16, 2019
[6]-Gingerol induces reactive oxygen species regulated mitochondrial cell death pathway in human epidermoid carcinoma
Nidhi Nigam1, Kulpreet Bhui, Sahdeo Prasad
1Proteomics Laboratory, Indian Institute of Toxicology Research (CSIR), M.G. Marg, Lucknow, India.
Abstract:
Since skin cancer incidence and prevalence is constantly rising up the charts despite all efforts, search for newer, better agents for protection and treatment is required. Ginger (Zingiber officinale Roscoe), a monocotyledonous herb, is widely used as a herbal medicine, given the presence of homologous phenolic ketones, of which [6]-gingerol is the major one. The quantity of [6]-gingerol in the fresh ginger rhizome was found to be 104-965 microg/g in common varieties of ginger available in Indian market. Herein, [6]-gingerol was assessed for its anti-apoptotic effects in human epidermoid carcinoma A431 cells. [6]-Gingerol treatment exhibited considerable cytotoxicity as indicated by growth inhibition of A431 cells mediated via generation of reactive oxygen species (ROS). Increase in ROS led to decrease in mitochondrial membrane potential (MMP) and subsequent induction of apoptosis. Results revealed that perturbations in mitochondrial membrane are associated with deregulation of Bax/Bcl-2 ratio at gene transcriptional level as well as protein level, where treatment with [6]-gingerol leads to up-regulation of Cytochrome-c and Apaf-1 subsequently culminating in triggering of Caspase cascade. These firmly suggest that [6]-gingerol can be effectively used for the treatment of skin cancer.
Insights
Ginger
Area of Science:
- Natural Products Chemistry
- Cancer Biology
- Cellular Toxicology
Background:
- Skin cancer incidence is increasing globally, necessitating novel therapeutic agents.
- Ginger (Zingiber officinale Roscoe) contains [6]-gingerol, a major bioactive phenolic ketone.
- The concentration of [6]-gingerol in ginger rhizomes varies, with significant levels found in Indian varieties.
Purpose of the Study:
- To investigate the anti-apoptotic and anti-cancer effects of [6]-gingerol.
- To evaluate the mechanism of action of [6]-gingerol in human epidermoid carcinoma A431 cells.
- To explore the potential of [6]-gingerol as a skin cancer treatment.
Main Methods:
- Treatment of A431 cells with purified [6]-gingerol.
- Assessment of cell viability and growth inhibition.
- Measurement of reactive oxygen species (ROS) generation.
- Analysis of mitochondrial membrane potential (MMP) and apoptosis markers.
- Evaluation of gene and protein expression of apoptosis-related molecules (Bax, Bcl-2, Cytochrome-c, Apaf-1, Caspases).
Main Results:
- [6]-Gingerol demonstrated significant cytotoxicity against A431 skin cancer cells.
- Cytotoxicity was mediated by increased reactive oxygen species (ROS) production.
- Elevated ROS levels led to decreased mitochondrial membrane potential (MMP) and induced apoptosis.
- Mitochondrial membrane perturbations were linked to altered Bax/Bcl-2 ratios.
- [6]-Gingerol treatment upregulated Cytochrome-c and Apaf-1, triggering the Caspase cascade.
Conclusions:
- [6]-Gingerol induces apoptosis in human epidermoid carcinoma cells via ROS generation and mitochondrial pathway.
- The study supports the potential of [6]-gingerol as a therapeutic agent for skin cancer treatment.
- Further research into [6]-gingerol's anti-cancer properties is warranted.