Rhabdastrellic Acid-A Induced Autophagy-Associated Cell Death through Blocking Akt Pathway in Human Cancer Cells

Abstract

BackgroundAutophagy is an evolutionarily conserved protein degradation pathway. A defect in autophagy may contribute to tumorigenesis. Autophagy inducers could have a potential function in tumor prevention and treatment.Methodology/Principal FindingsOur results showed that Rhabdastrellic acid-A, an isomalabaricane triterpenoid isolated from the sponge Rhabdastrella globostellata, inhibited proliferation of human cancer cell lines Hep3B and A549 and induced caspase-independent cell death in both the cell lines. Further investigation showed that Rhabdastrellic acid-A induced autophagy of cancer cells determined by YFP-LC3 punctation and increased LC3-II. The pretreatment with autophagy inhibitor 3-MA inhibited Rhabdastrellic acid-A-induced cell death. Knockdown of autophagy-related gene Atg5 inhibited Rhabdastrellic acid-A-induced cell death in A549 cells. Also, phospho-Akt and its downstream targets significantly decreased after treatment with Rhabdastrellic acid-A in both cancer cell lines. Transfection of constitutive active Akt plasmid abrogated autophagy and cell death induced by Rhabdastrellic acid-A.Conclusions/SignificanceThese results suggest that Rhabdastrellic acid-A could induce autophagy-associated cell death through blocking Akt pathway in cancer cells. It also provides the evidence that Rhabdastrellic acid-A deserves further investigation as a potential anticancer or cancer preventive agent.

Cytotoxic effect of evodiamine in SGC-7901 human gastric adenocarcinoma cells via simultaneous induction of apoptosis and autophagy

“…Next, the SGC-7901 cells were treated with 10 µM of evodiamine together with the autophagy inhibitor, 3-MA and were analyzed for cell death by flow cytometry using the PI staining assay. Cells stained with PI were considered as dead cells (41). Evodiamine-induced cell death was partially suppressed when the cells were treated in combination with the specific autophagy inhibitor, 3-MA (Fig.…”

“…Cells were centrifuged at 1000 rpm for 5 min; the cell pellet was rinsed twice with PBS, and then resuspended in 500 µl PBS and analyzed by flow cytometry using the PI staining assay. Cell death was measured by PI staining (41). Briefly SGC-7901 cells were trypsinized after the treatment with 10 µM of evodiamine in the presence of the autophagy inhibitor 3-methyladenine (3-MA) for 24 h and collected and resuspended with 1 ml PBS.…”

MK615, A Compound Extract from the Japanese Apricot “Prunus mume” Inhibits In vitro Cell Growth and Interleukin-8 Expression in Non-small Cell Lung Cancer Cells

“…These observations suggest that the induction of autophagy is one of the mechanisms of MK615-mediated cancer cell death. Of note, previous studies have demonstrated that several triterpenoids including ursolic acid induce autophagy in cancer cells [25,[29][30][31]. Although the precise mechanisms of MK615-mediated autophagy induction remain unknown, some of the triterpenoids in MK615may play important roles in the autophagic cell death of cancer cells.…”

Momordica cochinchinensis Spreng. seed extract suppresses breast cancer growth by inducing cell cycle arrest and apoptosis

“…Cells were stained with 0.5 ml staining solution (50 mg/ml PI, 100 mg/ml RNase, 0.2% Triton X-100) and cells were incubated in 37˚C for 30 min in the dark. Cell death was measured by flow cytometry (FACSCalibur; BD Biosciences, Franklin Lakes, NJ, USA) (25).…”