Targeting the Autophagy Pathway Using Ectopic Expression of Beclin 1 in Combination with Rapamycin in Drug-Resistant v-Ha-ras-Transformed NIH 3T3 Cells

Eum, Ki-Hwan; Lee, Michael

doi:10.1007/s10059-011-0034-6

Cited by 37 publications

(30 citation statements)

References 31 publications

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“…Beclin 1, another hallmark of autophagosomes, is a well-known protein with respect to the formation of autophagic vesicles (1,5). Western blotting results in the present study demonstrated that the expression level of beclin 1 protein was increased by 1.19-to 1.33-fold following treatment with Res, further corroborating the hypothesis that autophagy is induced by Res treatment (Fig.…”

Section: Inhibition Of Autophagy Attenuates the Res-induced Apoptosissupporting

confidence: 88%

“…Beclin 1 is required for the initiation stage in the formation of the autophagosome (1,5). In the present study, an increase in beclin1 protein expression levels was observed in Res-treated cells compared with the control, suggesting an enhanced induction of autophagy.…”

Section: Discussionsupporting

confidence: 61%

“…Beclin 1 was originally identified as a Bcl-2-interacting protein. Previous studies have demonstrated that beclin 1 and Bcl-2 interact in a multiprotein complex on the membrane of the endoplasmic reticulum; this observation in turn suggests a mechanism by which these proteins assist in mediating the intricate relationship between apoptosis and autophagy (1,16). It is known that beclin 1 generates a pro-apoptotic protein fragment and also interacts with the anti-apoptotic Bcl-2 family protein to inhibit autophagy and initiate mitochondrial apoptosis (22).…”

Section: Discussionmentioning

confidence: 99%

“…Autophagy has a cytoprotective function under stress conditions, such as during cytotoxic drug administration, and may result in increased drug resistance (1). It has been reported that autophagy increases the resistance of colorectal cancer stem-like cells to photodynamic therapy-induced apoptosis (1,27,28).…”

Section: Discussionmentioning

confidence: 99%

“…Autophagy associated with drug resistance is a major obstacle in cancer chemotherapy (1,2). It has been reported that autophagy-deficient tumors are typically more sensitive to chemotherapeutic agents than are their autophagy-proficient counterparts (3).…”

Section: Introductionmentioning

confidence: 99%

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Resveratrol induces autophagic apoptosis via the lysosomal cathepsin D pathway in human drug‑resistant K562/ADM leukemia cells

et al. 2018

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Abstract. The aim of the present study was to investigate the crosstalk between resveratrol (Res)-induced autophagy and apoptosis, and the molecular pathway by which autophagy leads to apoptotic death in drug-resistant K562/ADM leukemia cells. The viability of K562/ADM cells was determined using the MTT assay. The formation of autophagic vacuoles was detected using transmission electron microscopy and monodansylcadaverine (MDC) staining. Cell apoptosis was evaluated using flow cytometry. The expression of apoptosis-or autophagy-associated proteins was measured using western blotting. The results indicated that treatment with Res inhibited cell viability in a concentration-dependent manner. Furthermore, the numbers of MDC-positive fluorescent points, autophagic vacuoles and autolysosome-engulfed cytoplasmic materials were markedly increased in Res-treated K562/ADM cells compared with untreated cells, as determined using fluorescence microscopy and transmission electron microscopy. Res-induced apoptosis was associated with increased cleaved caspase-3 and B-cell lymphoma 2 associated X protein, and decreased B-cell lymphoma 2 (Bcl-2) protein expression levels when compared with the control (P<0.05). However, the proportion of apoptotic cells decreased from 69.6 to 41.0% (40 µmol/l Res) and from 77.3 to 58.8% (80 µmol/l Res) following pre-treatment with the autophagy inhibitor 3-methyladenine (P<0.01). The protein expression levels of microtubule-associated protein 1A/1B-light chain 3 and beclin 1, two markers of autophagy, were upregulated in Res-treated cells compared with the control (P<0.05). In addition, lysosomal cathepsin D (Cath D) release increased during Res-induced autophagy and apoptosis (P<0.05). The present results demonstrated that Res-induced apoptosis of K562/ADM cells was autophagy-dependent and the released Cath D may trigger caspase-dependent cell death through the Bcl-2 family of proteins. Furthermore, the present data indicate that to enhancement of the autophagy-cathepsin-apoptosis pathway may be an effective approach for overcoming anticancer drug resistance.

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Section: Inhibition Of Autophagy Attenuates the Res-induced Apoptosissupporting

confidence: 88%

Section: Discussionsupporting

confidence: 61%