Autophagy Involvement in Olanzapine-Mediated Cytotoxic Effects in Human Glioma Cells

Wang, Yixuan; Xu, Shuqing; Chen, Xianghui; Liu, Rui-Si; Liang, Zhong‐Qin

doi:10.7314/apjcp.2014.15.19.8107

Cited by 13 publications

(14 citation statements)

References 30 publications

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“…The results revealed that CTD also exhibited an ability to induce autophagy. Previous studies have demonstrated that autophagy is able to accelerate the incidence of apoptosis and suppress tumor cell multiplication and growth (25,26), which is line with the present results. The pathways involved in autophagy progression are complicated.…”

Section: Discussionsupporting

confidence: 93%

Cantharidin suppresses cell growth and migration, and activates autophagy in human non-small cell lung cancer cells

Liu

et al. 2018

Oncol Lett

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Abstract. Cantharidin (CTD), a component of Mylabris (blister beetle), is a traditional Chinese medicine that exerts an anticancer effect in multiple types of cancer cells. The aim of the present study was to investigate whether CTD exhibited anti-metastatic and inhibitory cell proliferation effects against human non-small cell lung cancer (NSCLC) A549 cells, and the possible underlying mechanism by which this occurs. The results of the present study demonstrated that CTD arrested proliferation, suppressed invasion and migration and induced apoptosis in A549 cells in vitro. Alterations of apoptosis-associated protein levels, including B-cell lymphoma-2 (Bcl-2), Bcl-associated X (Bax) and active caspase-3, were detected. Furthermore, the present study demonstrated that CTD activated autophagy through downregulation of p62 expression and upregulation of microtubule-associated proteins 1A/1B light chain 3B and Beclin-1 expression. Additionally, western blot analysis identified that CTD inhibited the phosphatidylinositol 3-kinase (PI3K)/RAC serine/threonine protein kinase (Akt)/mechanistic target of rapamycin (mTOR) signaling pathway in NSCLC, demonstrating that the levels of phosphorylated (p-)Akt, p-mTOR, phosphorylated ribosomal p70S6 protein kinase (p-p70-S6K) and cyclin D1 were significantly decreased following treatment with CTD. In conclusion, the results of the present study indicated that CTD impeded cell growth and migration by inhibiting PI3K/Akt/mTOR signaling in NSCLC, and promoted autophagy and apoptosis. CTD exhibited anticancer activity against NSCLC in vitro, revealing it as a potential candidate for the treatment of NSCLC.

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Section: Discussionsupporting

confidence: 93%

Cantharidin suppresses cell growth and migration, and activates autophagy in human non-small cell lung cancer cells

Liu

et al. 2018

Oncol Lett

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“…In recent years, olanzapine has been frequently used as a treatment for nausea and vomiting in cancer patients because of its known side effect (increased appetite) . Our previous experiments indicated that olanzapine could inhibit tumor proliferation both in vivo and in vitro . The current study verifies that this inhibitory effect is related to autophagy.…”

Section: Introductionsupporting

confidence: 75%

“…In general, NF‐κB increases tumorigenicity and has inhibitory effects on autophagy in cancer . In this study, we demonstrated that olanzapine activated autophagy through the inhibition of NF‐κB, ultimately promoting autophagy and apoptosis …”

Section: Introductionmentioning

confidence: 61%

“…Based on the CCK8 assay data, cell viability was reduced by olanzapine treatment. Accordingly, when combined with the autophagy inhibitor 3‐MA, the reduced cell viability was prevented, suggesting that olanzapine induced autophagy contributed to tumor cell death in glioma cells. Colony formation assays were also used to confirm the suppressive effects of olanzapine.…”

Section: Resultsmentioning

confidence: 99%

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Olanzapine induced autophagy through suppression of NF‐κB activation in human glioma cells

et al. 2019

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Summary Aims Our laboratory previously reported that olanzapine treatment inhibited growth of glioma cell lines and hypothesized that autophagy may be involved in the proliferation inhibitory effects of olanzapine. However, the mechanisms of olanzapine‐contributed autophagy activation are unclear. Methods The inhibitory effects of olanzapine on glioma cells were evaluated by CCK8 assay, Hoechst 33258 staining and annexin V‐FITC/PI staining. Western blotting, nuclear separation techniques, and immunofluorescence assays were used to investigate the relationship between the inhibition of NF‐κB and autophagy activation by olanzapine. Results In this work, we verified that olanzapine increased autophagic flux and autophagic vesicles. In addition, we confirmed that autophagy was related to NF‐κB inhibition in cancer progression, especially with the nuclear translocation of p65. Furthermore, we demonstrated that autophagy induced by olanzapine could be impaired with TNFα cotreatment. We also found that olanzapine had an inhibitory effect on T98 cells with positive MGMT protein expression, which may involve the inhibition of MGMT through effects on NF‐κB. Conclusions Our findings identify a pathway by which olanzapine induces autophagy by depressing NF‐κB in a glioma cell line, providing evidence which supports the use of olanzapine as a potential anticancer drug.

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“…Autophagy and apoptosis are intricately linked: Both are genetically regulated and evolutionarily conserved processes that can determine cell fate; however, while apoptosis invariably leads to cancer cell death, autophagy may occur as a survival response to growth factors or nutrient deprivation, but may also act as an important molecular mechanism for tumor cell suicide (14). Numerous studies have indicated that if cellular damage is extensive or if apoptosis is compromised, autophagy may be used to kill cells (15,16). …”

Section: Introductionmentioning

confidence: 99%

Rottlerin-induced autophagy leads to apoptosis in bladder cancer cells

Peng

Zhang

et al. 2016

Oncology Letters

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It has been well-established that apoptosis contributes to cancer cell death; however, the role of autophagy in cancer cell death remains unclear. The aim of the present study was to investigate the effects of rottlerin, a traditional Indian medicine, on cell growth inhibition and autophagy in EJ human bladder carcinoma cells in vitro. Cell viability, measured by MTT assay, was found to be suppressed in a dose- and time-dependent manner. In addition, apoptosis was significantly increased in cells treated with rottlerin, as indicated by increased annexin V-fluorescein isothiocyanate/propidium iodide staining and changes in the cell cycle distribution that indicated blockage at G1 phase. Rottlerin treatment also enhanced the activation of autophagy, with increased expression of microtubule-associated protein 1 light chain 3 (LC3)-II and the appearance of autophagosomes. The increased level of LC3-II and autophagosomes suggests that autophagy may contribute to apoptosis in these cells. In addition, no apparent alterations in the levels of pro-caspase-3, cleaved caspase-3, total poly (ADP ribose) polymerase (PARP) and cleaved-PARP were observed in cells treated with rottlerin, which indicates that caspases may not serve a key role during the process of apoptosis induced by rottlerin. Therefore, the results of the present study indicate that rottlerin promotes apoptosis and arrests the cell cycle in EJ cells, which may be caused by autophagy activation.

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Autophagy Involvement in Olanzapine-Mediated Cytotoxic Effects in Human Glioma Cells

Cited by 13 publications

References 30 publications

Cantharidin suppresses cell growth and migration, and activates autophagy in human non-small cell lung cancer cells

Cantharidin suppresses cell growth and migration, and activates autophagy in human non-small cell lung cancer cells

Olanzapine induced autophagy through suppression of NF‐κB activation in human glioma cells

Rottlerin-induced autophagy leads to apoptosis in bladder cancer cells

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