Proliferative inhibition, cell-cycle dysregulation, and induction of apoptosis by ursolic acid in human non-small cell lung cancer A549 cells.
Ursolic acid (UA) is a pentacyclic triterpene compound isolated from many types of medicinal plants and is present in human diet. It has been reported to possess a wide range of pharmacological properties, and is one of the most promising chemopreventive agents for cancer. Here, we report that UA inhibits the cell proliferation of human lung cancer cell line A549 and provide a molecular understanding of this effect. The results showed that UA blocked cell cycle progression in the G1 phase that was associated with a marked decrease in the protein expression of cyclin D1, D2, and E and their activating partner cdk2, 4, and 6 with concomitant induction of p21/WAF1. This accumulation of p21/WAF1 might be through a p53-dependent manner. Further, UA treatment also resulted in the triggering of apoptosis as determined by DNA fragmentation assay. This effect was found to correlate with the up-regulation of Fas/APO-1, Fas ligand, and Bax, and down-regulation of NF-kappaB, Bcl-2, and Bcl-XL. Taken together, our study indicated that UA might be a potential chemopreventive agent for lung cancer.
Hsu
Ya-Ling
YL
Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, No. 100, Shin-Chuan 1st Road, 807, Taiwan.
Kuo
Po-Lin
PL
Lin
Chun-Ching
CC
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
D000972:Antineoplastic Agents, Phytogenic; D018797:Cell Cycle Proteins; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D014315:Triterpenes; D000097245:Ursolic Acid; C505661:FASLG protein, human