Isoalantolactone exerts anticancer effects on human HEC-1-B endometrial cancer cells via induction of ROS mediated apoptosis and inhibition of MEK/ERK signalling pathway.

Abstract

Isoalantolactone has been shown to inhibit the growth of different cancer cells. The objective of the present study was to evaluate the effects of isoalantolactone on the proliferation of endometrial cancer HEC-1-B cells. Results showed that isoalantolactone suppressed the proliferation of HEC-1-B cells in a concentration-dependent manner and exhibited an IC50 of 10 µM. The cytotoxic effects of isoalantolactone were relatively lower against the normal THESC cells. Mechanistic studies revealed apoptosis to be responsible for the isoalantolactone mediated antiproliferative effects. Annexin V/PI assay showed that the percentage of the apoptotic HEC-1B cells increased from 3.74% in untreated cells to 28.9% at 20 µM isoalantolactone. The expression of Bax was significantly increased and that of Bcl-2 was decreased in isoalantolactone treated HEC-1B cells. Analysis of ROS levels revealed that the ROS levels of HEC-1B cells increased with the increase in concentration of isoalantolactone. The ROS levels increased to 210% of the control at 20 µM isoalantolactone. The wound healing and the transwell assays showed that migration and invasion of the HEC-1B cells was significantly decreased upon isoalantolactone treatment. Finally, the effects of isoalantolactone were also evaluated on the MEK/ERK signalling pathway. It was found that isoalantolactone could concentration-dependently block the expression of p-MEK and p-ERK. Taken together, the results suggest that isoalantolactone could prove to be a lead molecule in the development of chemotherapy for endometrial cancer.

• Authors: Fang Hu, Ping Yang
• Journal: Acta biochimica Polonica (Acta Biochim Pol) Vol. 69 Issue 2 Pg. 453-458 (Jun 08 2022) ISSN: 1734-154X [Electronic] Poland
• PMID: 35675539 (Publication Type: Journal Article)

Chemical References

• Reactive Oxygen Species
• Sesquiterpenes
• isoalantolactone
• Mitogen-Activated Protein Kinase Kinases

Topics

• Apoptosis
• Cell Line, Tumor
• Cell Proliferation
• Endometrial Neoplasms (drug therapy, metabolism)
• Female
• Humans
• MAP Kinase Signaling System
• Mitogen-Activated Protein Kinase Kinases (pharmacology, therapeutic use)
• Reactive Oxygen Species (metabolism)
• Sesquiterpenes