Phytol Induces Apoptosis and ROS-Mediated Protective Autophagy in Human Gastric Adenocarcinoma AGS Cells

Abstract

Phytol, a diterpene alcohol produced from chlorophyll, is used widely as a food additive and an aromatic ingredient. However, the molecular mechanisms behind the cytotoxic effects of phytol in cancer cells are not understood. The current study demonstrated that phytol induces apoptosis in human gastric adenocarcinoma AGS cells, as evidenced by an increased cell population in the sub-G1 phase, downregulation of Bcl-2, upregulation of Bax, the activation of caspase-9 and -3, PARP cleavage, and depolarization of the mitochondrial membrane. In addition, phytol induced autophagy, as evidenced by the induction of acidic vesicle accumulation, the conversion of microtubule-associated protein LC3-I to LC3-II, and the suppression of Akt, mTOR, and p70S6K phosphorylation. Most importantly, pretreatment with chloroquine, a lysosomal inhibitor, strongly augmented phytol-induced apoptosis in AGS cells, suggesting that phytol could induce protective autophagy. Furthermore, co-treatment with a reactive oxygen species (ROS) scavenger enhanced the phytol-induced cytotoxicity, which is accompanied by the decrease in the levels of p62 as well as the percentage of acidic vesicular organelles (AVOs) positive cells, suggesting that the cytoprotective Nrf2 pathway was induced by phytol. Taken together, these findings provide valuable insights into the mechanisms by which phytol induces cell death in AGS cells.

Essential oil of Cyphostemma juttae (Vitaceae): Chemical composition and antitumor mechanism in triple negative breast cancer cells

“…Moreover, in the same cancer models, the essential oil showed antitumor capacities in the terms of cytotoxic and pro-oxidant activities and partially pro-apoptotic effects proven by preliminary cytofluorimetric analysis by propidium iodide where only a modest block in preG0-G1 position dose-dependent is observed in all cell lines and also shown in other studies [23]. It is very interesting to note that the essential oil exerts an inhibitory effect on the transcription of the P-glycoprotein the ABCB1 multi-drug efflux pump (MDR).…”

Pro-Apoptotic Activity of French Polynesian Padina pavonica Extract on Human Osteosarcoma Cells

“…In EPP, phytol—an acyclic monounsaturated diterpene alcohol and constituent of chlorophyll—was found in a remarkable amount. The anticancer activity of phytol against several tumor cell lines in vitro has been assessed [30,31,32], as well as its capacity to induce the apoptosis in hepatocellular carcinoma cells [33] and in human gastric adenocarcinoma AGS [34].…”

GC‐MS Based Metabolite Profiling, Antioxidant and Antimicrobial Properties of Different Solvent Extracts of Malaysian Plectranthus amboinicus Leaves

“…Similarly, the occurrence of these compounds is also evidenced in many medicinal plants leaves extracted with methanol [5, 33, 34]. Phytol is an important diterpene that possesses antimicrobial, antioxidant, and anticancer activities [5, 35, 36]. Hexadecanoic acid is known to exhibit strong antimicrobial and anti-inflammatory activity [5, 37].…”