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.

Toxicology Research
|June 18, 2021
PubMed

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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