Targeting autophagy potentiates chemotherapy-induced apoptosis and proliferation inhibition in hepatocarcinoma cells

Guo, Xianling; Li, Ding; Hu, Fei; Song, Jianrui; Zhang, Shanshan; Deng, Wei; Sun, Kai; Zhao, Qinqin; Xie, Xuqin; Yang, Song; Wu, Mengchao; Wei, Lixin

doi:10.1016/j.canlet.2012.03.002

Cited by 164 publications

(114 citation statements)

References 38 publications

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“…Among them, CQ and its derivatives have gained increasing attention due to their favorable pharmacological properties and physiological tolerance as evidenced by their long history of use as anti-malarial agents and in diseases such as rheumatoid arthritis. CQ inhibits lysosomal acidification, which blocks the terminal stage of autophagy and has indeed been shown to potentiate the anticancer effects of various chemotherapeutic drugs both in vitro and in vivo (32)(33)(34)(35). Currently, multiple clinical trials using CQ as a sensitizing reagent, in combination with standard cancer therapies, are under evaluation in different tumor types, including lung cancer, glioblastoma multiforme, multiple myeloma, breast cancer, melanoma, colon cancer, prostate cancer, and advanced solid tumors unresponsive to chemotherapy (http:// clinicaltrials.gov).…”

Section: Discussionmentioning

confidence: 99%

Autophagy inhibition enhances sensitivity of endometrial carcinoma cells to paclitaxel

Liu

2015

International Journal of Oncology

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Abstract. Autophagy has been shown to be involved in cancer cell resistance to chemotherapy. Paclitaxel, a widely used chemotherapeutic drug, was demonstrated to induce autophagy in various cancer cells. Therefore, we sought to evaluate the role of autophagy on the paclitaxel-induced cell death in endometrial carcinoma. In this study, we found that paclitaxel induced autophagy in paclitaxel-insensitive HEC-1A and JEC cells, exhibiting an increased microtubule associated protein 1 light chain 3 (LC3)-II/LC3-I ratio, a decrease in p62/ SQSTM1 abundance, the upregulation of Beclin 1 expression and punctate dots of yellow fluorescent protein (YFP)-LC3 in the cytosol. Paclitaxel-mediated cell death was further potentiated by pretreatment with autophagy inhibitor chloroquine (CQ) or shRNA against the autophagic gene beclin 1. Moreover, paclitaxel stimulated reactive oxygen species (ROS) generation, and inhibition of the ROS by antioxidant N-acetyl-cysteine (NAC) blocked paclitaxel-induced autophagy, indicating that paclitaxel-induced autophagy in endometrial carcinoma cells is mediated by ROS. These findings suggest that paclitaxelelicited autophagic response plays a protective role that impedes the eventual death of endometrial carcinoma cell, and that autophagy-inhibitor therapy could be an effective and potent strategy to improve paclitaxel treatment outcomes in the treatment of endometrial carcinoma.

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Section: Discussionmentioning

confidence: 99%

Autophagy inhibition enhances sensitivity of endometrial carcinoma cells to paclitaxel

Liu

2015

International Journal of Oncology

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“…52 However, our results seem to be consistent with those of previous studies in that the inhibition of autophagy contributed to the cell's sensitivity to chemo-and radio-resistance. 53,54 By inference, the role of autophagy in tumorigenesis and cancer therapy appears to be contextual, functioning as a double-edged sword depending on the status of the tumor cells. In certain cancer treatments, autophagy is required to induce robust cell death in tumor cells as GSCs.…”

Section: Discussionmentioning

confidence: 99%

Suberoylanilide hydroxamic acid (SAHA) causes tumor growth slowdown and triggers autophagy in glioblastoma stem cells

et al. 2013

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“…On the other hand, mounting evidence suggests that autophagy may have cancer promoting effect [91] through providing stress tolerance, and inhibition of apoptosis [93]. These controversies are important and needs further studies to clarify because many current cancer therapy agents activate autophagy [94]. We observed that Atg5 expression was inversely correlated with serum levels and intra-hepatic expression of mTOR.…”

Section: Discussionmentioning

confidence: 74%

Target of Rapamycin (TOR) and Autophagy in Chronic Hepatitis C Virus Infection: Relation to Disease Activity

Lashen¹

2017

JLRDT

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Background: In chronic hepatitis C (CHC) infection, liver disease progression results from viral persistence. Deregulation of target of rapamycin (TOR) signaling and autophagy is detected in viral infections and cancer. We studied the role of TOR and autophagy in the progression of CHC infection.Methods: 54 patients infected with HCV, [27 with CHC; 13 with cirrhosis and 14 with hepatocellular carcinoma (HCC)]; and 15 healthy subjects were included. Quantification of serum TOR was determined using enzyme linked immunosorbent assay. Tissue samples were immune-stained using TOR and autophagy protein 5 (Atg5) polyclonal antibodies. Expression of TOR and Atg5 was scored semi-quantitatively.Results: Expression and serum TOR were higher in HCC patients compared to patients without HCC (P< 0.05). Serum and expression of TOR were positively correlated to inflammation, fibrosis, steatosis and tumor characteristics (Alpha-fetoprotein, maximum diameter, tumor grade and CLIP stage) (P<0.05). Expression of Atg5 was inversely correlated with inflammation, fibrosis and tumor characteristics (P<0.05), Atg5 showed significant inverse correlation with serum and intra-hepatic expression of TOR (P<0.05). Serum TOR showed high sensitivity and specificity in discriminating infected patients with and without HCC at a cut-off value of 4.55 ng/ml [Area under ROC curve = 0.970]. Conclusion:Activation of TOR plays an important role in progression of HCV related liver disease possibly though autophagy suppression and they could be a potential therapeutic target. Serum TOR is a potential seromarker in discriminating HCV infected patients with and without HCC with high sensitivity and specificity.

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Targeting autophagy potentiates chemotherapy-induced apoptosis and proliferation inhibition in hepatocarcinoma cells

Cited by 164 publications

References 38 publications

Autophagy inhibition enhances sensitivity of endometrial carcinoma cells to paclitaxel

Autophagy inhibition enhances sensitivity of endometrial carcinoma cells to paclitaxel

Suberoylanilide hydroxamic acid (SAHA) causes tumor growth slowdown and triggers autophagy in glioblastoma stem cells

Target of Rapamycin (TOR) and Autophagy in Chronic Hepatitis C Virus Infection: Relation to Disease Activity

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