Trilinolein inhibits proliferation of human non-small cell lung carcinoma A549 through the modulation of PI3K/Akt pathway.

Abstract

Trilinolein has been identified as one of the active constituents isolated from Panax notoginseng used widely in traditional Chinese medicine. Protective actions of Panax notoginseng against cerebral ischemia, beneficial effects on the cardiovascular system, and hemostatic, antioxidant, hypolipidemic, hepatoprotective, renoprotective and estrogen-like activities have been illustrated. In the present study, the effects of trilinolein on the growth of non-small cell lung carcinoma A549 were investigated. It was found that the exposure of A549 cells to trilinolein resulted in the growth inhibition and the induction of apoptosis in a dose- and time- dependent manner. Trilinolein treatment induced the upregulation of pro-apoptotic Bax, downregulation of anti-apoptotic Bcl-2 expression, which was associated with the proteolytic activation of caspases and the concomitant degradation of poly(ADP-ribose) polymerase (PARP) protein. Intracellular reactive oxygen species seem to play a role in the trilinolein-induced apoptosis, since ROS were produced early in the trilinolein treatment. Moreover, the activity of PI3K/Akt was downregulated in trilinolein-treated cells. Our results demonstrated that the most important regulators of trilinolein-induced apoptosis are Bcl-2 family and caspase-3, which are associated with cytochrome c release and dephosphorylation on the Akt signaling pathway.

• Authors: Pei-Yu Chou, Guan-Jhong Huang, Chun-Hsu Pan, Yi-Chung Chien, Ying-Yi Chen, Chieh-Hsi Wu, Ming-Jyh Sheu, Hsu-Chen Cheng
• Journal: The American journal of Chinese medicine (Am J Chin Med) Vol. 39 Issue 4 Pg. 803-15 ( 2011) ISSN: 1793-6853 [Electronic] Singapore
• PMID: 21721158 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Plant Extracts
• Proto-Oncogene Proteins c-bcl-2
• Reactive Oxygen Species
• Triglycerides
• bcl-2-Associated X Protein
• Cytochromes c
• Poly(ADP-ribose) Polymerases
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Caspase 3
• trilinolein

Topics

• Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy, metabolism)
• Caspase 3 (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cytochromes c (metabolism)
• Dose-Response Relationship, Drug
• Humans
• Panax notoginseng (chemistry)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation
• Phytotherapy
• Plant Extracts (pharmacology, therapeutic use)
• Poly(ADP-ribose) Polymerases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Triglycerides (pharmacology, therapeutic use)
• bcl-2-Associated X Protein (metabolism)