Induction of α-Phellandrene on Autophagy in Human Liver Tumor Cells

Abstract

α-Phellandrene (α-PA) is a cyclic monoterpene. To investigate the induction of autophagy by α-PA and its mechanism, human liver tumor cells (J5) were incubated with α-PA and analyzed for cell viability and the molecular regulation of pre-autophagosome origination and autophagosome formation. According to the results, PI3K-I, mTOR, and Akt protein levels were decreased after α-PA treatment compared to those of the control group (p < 0.05). The phosphorylation of Bcl-2, and PI3K-III, LC3-II and Beclin-1 protein levels in J5 cells were increased after α-PA treatment (p < 0.05). In addition, α-PA up-regulated nuclear p53 and down-regulated cytoplasmic p53 expression in J5 cells. The NF-κB pathway was activated, as indicated by increase in cytosolic phosphorylated IκB, nuclear NF-κB levels, and the DNA-binding activity of NF-κB after α-PA treatment in J5 cells (p < 0.05). These results suggest that α-PA can induce J5 cell autophagy by regulating mTOR and LC-3II expression, p53 signaling, and NF-κB activation in J5 cells.

Vitexin suppresses autophagy to induce apoptosis in hepatocellular carcinoma via activation of the JNK signaling pathway

“…Increasing evidence has been presented that autophagy plays a crucial role in tumor suppression [18]. Findings from a number of reports directed at assessing natural extracts or traditional herbs for use in cancer treatment have revealed that their cytotoxic effects involve the induction and regulation of autophagy [19, 20]. Autophagy can serve as a means to promote cell survival or, contrarily, cell death in tumor cells treated with chemotherapeutic agents [21].…”

Comprehensive Analysis of the Chemical Composition and In Vitro Cytotoxic Mechanisms of Pallines Spinosa Flower and Leaf Essential Oils Against Breast Cancer Cells

“…α-phellandrene also alters the expression of cell cycle checkpoint genes such as cyclin G2 and the CDK inhibitor p21, in addition to several apoptosis regulatory factors including caspases [52]. Hsieh LC et al [53] have demonstrated that sub-micromolar concentrations of α-phellandrene promote cell death by autophagy through modulating the expression of mTOR and LC-3II, p53 signaling and NF-KB activation in J5 liver tumor cells. In addition, the toxicity of this compound involves necrosis when tested in liver cancer cell lines [54].…”

“…This is particularly obvious with the finding that the general caspase-inhibitor is only able to reverse ∼30% of the oil induced apoptosis in MDA-MB-2 31 compared to ∼60% in MCF-7 cells. The fact that the essential oils of P. spinosa contain compounds that promote cell death by autophagy [53], activation of MAPKs [50], production of ROS [51] and cell cycle arrest [51], proposes that they may also contribute to the cytotoxicity of F-PSEO and L-PSEO.…”

Kazakh Ziziphora Species as Sources of Bioactive Substances

“…rigida (0.1%) [21] Z. clinopodioides subsp. bungeana [201] Z. tenuior (0.48%) [94,179] Insecticidal activity against various species of insects [192,193]; larvicidal activity against various mosquito species [205,206] Antinociceptive activity assessed in various chemical-induced nociception models in rodents [207,208] Antidepressant activity in rats [208] Induction of autophagy in human liver tumour cells [209]; induction of necrosis [210]; induction of apoptosis in mice leukaemia WEHI-3 cells in vitro [211]; promotion of the immune response by increasing the level of T-cells, monocytes and macrophages in BALB/c mice in vivo [212] Molecules 2016, 21, 826 14 of 53…”

“…clinopodioides (2.0%) [184] Inhibition of P-glycoprotein-mediated transport of different substances [213] Suppression of CNS in mice [214,215] Some topical anti-inflammatory activity in carrageenan-induced paw edema in rats [216] Antioxidant activity in various free radical scavenging tests [217,218] Antifungal activity tested against some food spoilage yeasts [219] Larvicidal activity against mosquitoes Aedes aegypti and A. albopictus [206] Antiviral activity against herpes simplex virus type 1 in vitro [220] Review on some effects on cardiovascular system [221] Trypanocidal activity against Trypanosoma evansi [222] Z. tenuior (0.48%) [94,179] α-Phellandrene (35) Z. clinopodioides (0.3%) [184] Insecticidal activity against various species of insects [192,193]; larvicidal activity against various mosquito species [205,206] Antinociceptive activity assessed in various chemical-induced nociception models in rodents [207,208] Antidepressant activity in rats [208] Induction of autophagy in human liver tumour cells [209]; induction of necrosis [210]; induction of apoptosis in mice leukaemia WEHI-3 cells in vitro [211]; promotion of the immune response by increasing the level of T-cells, monocytes and macrophages in BALB/c mice in vivo [212] α-Terpinene (36)…”