Ampelopsin‐induced autophagy protects breast cancer cells from apoptosis through Akt‐mTOR pathway via endoplasmic reticulum stress

Abstract

Our previous study has shown that ampelopsin (AMP), a flavonol mainly found in Ampelopsis grossedentata, could induce cell death in human breast cancer cells via reactive oxygen species generation and endoplasmic reticulum (ER) stress pathway. Here, we examined whether autophagy is activated in AMP-treated breast cancer cells and, if so, sought to find the exact role and underlying molecular profile of autophagy in AMP-induced cell death. Our results showed that AMP treatment activated autophagy in MDA-MB-231 and MCF-7 breast cancer cells, as evidenced by the accumulation of autophagosomes, an increase of microtubule-associated protein 1 light chain 3 beta-2 (LC3B-II) and the conversion of LC3B-I to LC3B-II, the degradation of the selective autophagic target p62/SQSTM1, and the formation of green fluorescent protein (GFP)-LC3 puncta. Blockage of autophagy augmented AMP-induced cell death, suggesting that autophagy has cytoprotective effects. Meanwhile, AMP treatment suppressed Akt-mammalian target of rapamycin (mTOR) pathway as evidenced by dose- and time-dependent decrease of the phosphorylation of Akt, mTOR and ribosomal protein S6 kinase (p70S6K), whereas Akt activator insulin-like growth factor-1 (IGF-1) pretreatment partially restored Akt-mTOR pathway inhibited by AMP and decreased AMP-inuduced autophagy, signifying that AMP activated autophagy via inhibition of the Akt-mTOR pathway. Additionally, blocking ER stress not only reduced autophagy induction, but also alleviated inhibition of the Akt-mTOR pathway induced by AMP, suggesting that activation of ER stress was involved in induction of autophagy and inhibition of the Akt-mTOR pathway. Taken together, these findings indicate that AMP induces protective autophagy in human breast cancer cells through Akt-mTOR pathway via ER stress.

Linc00152 Functions as a Competing Endogenous RNA to Confer Oxaliplatin Resistance and Holds Prognostic Values in Colon Cancer

“…47 To determine whether Linc00152 contributes to chemoresistance through activating the AKT pathway, the specific AKT signaling inhibitor MK2206 and activator IGF-1 were used in the research, respectively. 48,49 Consistent with the speculation, increased cell response to L-OHP was observed when AKT signaling pathway was blocked in Linc00152-overexpressing cells. On the other hand, activation of the AKT signaling pathway decreased the sensitivity of cells to L-OHP induced apoptosis in 1 5 9 13 17 21 25 29 33 37 41 45 49 53 57 61 65 69 73 77 81 85 89 93 97 101 105 109 113 117 121 125 129 These results demonstrated that Linc00152 contributed to L-OHP resistance at least in part through modulating the miR-193a-3p/ ERBB4/AKT axis.…”

Basic Studies on Chemopreventive Properties of Quercetin and Curcumin and Other Plant-origin Compounds in Ovarian Cancer Cells – A Mini-review

“…with 80 mg/kg of quercetin twice a week; 30 mg/kg 3MA twice a week; a combination of 30 mg/kg 3 MA and 80 mg/kg of quercetin twice a week; or a vehicle control injected with the same volume of saline for 4 weeks [78]. The results of this study are consistent with the trend of predecessor studies [56,60,77] showing that quercetin has the potential to induce protective autophagy in cancer cells through AKT-mTOR and hypoxia-induced factor 1α signaling [79,80] and in this way to induce autophagy in ovarian cancer cells [81].…”

p8 attenuates the apoptosis induced by dihydroartemisinin in cancer cells through promoting autophagy

“…20 The major pathway of ER stress is unfolded protein response (UPR), which is identified to recover ER homeostasis and promote cell survival. 21 In addition, ER stress has proved to be one of the inducers of autophagy. 22 Interestingly, DHA induced-ER stress has been observed in several tumor cells, 23,24 and our previous studies have demonstrated that DHA both induce apoptosis and autophagy in various cancer cells.…”