TEEG Induced A549 Cell Autophagy by Regulating the PI3K/AKT/mTOR Signaling Pathway

Abstract

TEEG (3β,16β,23-trihydroxy-13,28-epoxyurs-11-ene-3-O-β-D-glucopyranoside) is derived from the chloroform extract of the Chinese medicine formula Shenqi San (CE-SS). In the present study, we aimed to elucidate the anticancer effect and possible molecular mechanism underlying the action of TEEG against the human non-small cell lung cancer (NSCLC) cell line A549 in vitro. A549 cells were incubated with different concentrations of TEEG. Cell proliferation was assessed by MTT assay. Autophagy was evaluated by immunofluorescence staining. Autophagy-associated proteins were examined by Western blot analysis. TEEG markedly inhibited A549 cell proliferation in a concentration-dependent manner. Immunofluorescence staining showed that TEEG induced autophagy in A549 cells. The LC3-II : LC3-I conversion ratio and the expression of Beclin-1, Atg5, Atg7, and Atg12 increased with the concentration of TEEG. In addition, increased TEEG concentration enhanced the expression of Class III p-PI3K and reduced the expression of Class I p-PI3K, p-AKT, p-mTOR, and p-P70S6K. These results indicate that TEEG induces autophagy of A549 cells through regulation of the PI3K/AKT/mTOR signaling pathway.

Cyclophilin A inhibits A549 cell oxidative stress and apoptosis by modulating the PI3K/Akt/mTOR signaling pathway

“…These findings suggest that CypA can protect A549 cells from H2O2induced oxidative injury and apoptosis.In many cancers, including lung carcinoma, the PI3K/AKT/mTOR pathway is hyperactive, thus blocking apoptosis through the regulation of downstream signaling molecules, such as inhibiting the activation of Caspase-7, as well inactivating Bcl-2 family members[50,51]. Emerging evidence has demonstrated that activation of the PI3K/Akt signaling pathway protects A549 cells from oxidative stress and apoptosis[52][53][54]. Intriguingly, a previous study reported that extracellular CypA promotes platelet adhesion via cluster of differentiation 147 (CD147)-mediated PI3K/Aktsignaling[55].…”

Apoptosis of T-acute lymphoblastic leukemia cells is induced by the combination of PI3K and autophagy inhibitors

“…Meanwhile autophagy provides nutritional support to cells under different stress conditions and is regarded to be one of the physiological processes that can affect cell survival [30]. Autophagy in lung cancer can be inhibited by oncogenes, such as PI3K and mTOR, while it can be activated by autophagy-related proteins, such as ATG5, ATG12 and Beclin-1 [31]. In our work, after the treatment of PX-866 and PI-103, the expression of ATG5, ATG12 and Beclin-1 in CCRF-CEM and Jurkat cells was dramatically elevated.…”