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Ursolic acid disturbs ROS homeostasis and regulates survival-associated gene expression to induce apoptosis in
Laxminarayan Rawat1, Vijayashree Nayak1
1Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, K.K. Birla Goa Campus, NH-17B, Zuarinagar, Goa, 403726, India.
Abstract:
Ursolic acid is a natural compound possessing several therapeutic properties including anticancer potential. In present study, cytotoxic and antimetastatic properties of ursolic acid were investigated in intestinal cancer cell lines INT-407 and HCT-116. The cells growth and number were decreased in a dose- and time-dependent manner in both the cell lines. It also increases reactive oxygen species levels in the cells in order to induce apoptosis. Ursolic acid was found to be a significant inhibitor of cancer cells migration and gene expression of migration markers FN1, CDH2, CTNNB1 and TWIST was also downregulated. Ursolic acid treatment downregulated the gene expression of survival factors BCL-2, SURVIVIN, NFKB and SP1, while upregulated the growth-restricting genes BAX, P21 and P53. These results indicate that ursolic acid has anticancer and antimetastatic properties against intestinal cancer. These properties could be beneficial in cancer treatment and could be used as complementary medicine.
Insights
Ursolic acid, a natural compound, exhibits significant anticancer and antimetastatic properties in intestinal cancer cells. It effectively inhibits cell growth, migration, and induces apoptosis, suggesting its potential as a complementary cancer therapy.
Area of Science:
- Natural Products Chemistry
- Cancer Biology
- Molecular Oncology
Background:
- Ursolic acid is a pentacyclic triterpenoid found in various plants.
- It has demonstrated diverse pharmacological activities, including anti-inflammatory and antioxidant effects.
- Preliminary studies suggest potential anticancer effects, warranting further investigation.
Purpose of the Study:
- To investigate the cytotoxic and antimetastatic effects of ursolic acid on intestinal cancer cell lines.
- To elucidate the molecular mechanisms underlying ursolic acid's action, including apoptosis induction and gene expression modulation.
- To evaluate the potential of ursolic acid as a complementary therapeutic agent for intestinal cancer.
Main Methods:
- Treatment of INT-407 and HCT-116 intestinal cancer cell lines with varying concentrations of ursolic acid.
- Assessment of cell viability, proliferation, and apoptosis induction.
- Analysis of cell migration and invasion assays.
- Quantitative real-time PCR to determine the gene expression levels of key markers involved in cell migration, survival, and apoptosis.
Main Results:
- Ursolic acid significantly reduced cell growth and number in a dose- and time-dependent manner.
- Increased reactive oxygen species (ROS) levels were observed, leading to apoptosis induction.
- Ursolic acid markedly inhibited cancer cell migration and downregulated the expression of migration markers (FN1, CDH2, CTNNB1, TWIST).
- Gene expression analysis revealed downregulation of survival factors (BCL-2, SURVIVIN, NFKB, SP1) and upregulation of growth-restricting genes (BAX, P21, P53).
Conclusions:
- Ursolic acid possesses significant anticancer and antimetastatic properties against intestinal cancer cell lines.
- The compound induces apoptosis and inhibits cell migration through modulation of specific gene expression pathways.
- Ursolic acid shows promise as a complementary therapeutic agent in intestinal cancer treatment.
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