Phytol shows anti-angiogenic activity and induces apoptosis in A549 cells by depolarizing the mitochondrial membrane potential

• Published in: Biomedicine & pharmacotherapy Vol. 105; pp. 742 - 752
• Main Authors: Sakthivel, Ravi, Malar, Dicson Sheeja, Devi, Kasi Pandima
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.09.2018
• Subjects: A549 Cells; Adenocarcinoma; Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - toxicity; Apoptosis - drug effects; CAM assay; Cell Cycle - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Dose-Response Relationship, Drug; Humans; Membrane Potential, Mitochondrial - drug effects; Mitochondrial membrane potential; Phytol; Phytol - pharmacology; Phytol - toxicity; PI staining; Time Factors; Western blotting; Adenocarcinoma; CAM assay; Phytol; PI staining; Western blotting; Mitochondrial membrane potential
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.06.035

[Display omitted] In the present study, the antiproliferative activity of phytol and its mechanism of action against human lung adenocarcinoma cell line A549 were studied in detail. Results showed that phytol exhibited potent antiproliferative activity against A549 cells in a dose and time-dependent manner with an IC50 value of 70.81 ± 0.32 μM and 60.7 ± 0.47 μM at 24 and 48 h, respectively. Phytol showed no adverse toxic effect in normal human lung cells (L-132), but mild toxic effect was observed when treated with maximum dose (67 and 84 μM). No membrane-damaging effect was evidenced by PI staining and SEM analysis. The results of mitochondrial membrane potential analysis, cell cycle analysis, FT-IR and Western blotting analysis clearly demonstrated the molecular mechanism of phytol as induction of apoptosis in A549 cells, as evidenced by formation of shrinked cell morphology with membrane blebbing, depolarization of mitochondrial membrane potential, increased cell population in the sub-G0 phase, band variation in the DNA and lipid region, downregulation of Bcl-2, upregulation of Bax and the activation of caspase-9 and -3. In addition, phytol inhibited the CAM vascular growth as evidenced by CAM assay, which positively suggests that phytol has anti-angiogenic potential. Taken together, these findings clearly demonstrate the mode of action by which phytol induces cell death in A549 lung adenocarcinoma cells.