The BH3 mimetic S1 induces autophagy through ER stress and disruption of Bcl-2/Beclin 1 interaction in human glioma U251 cells

Zhong, Jian‐Jiang; Xu, Ye; Huiuk, Yi; Su, Jing; Yu, Huimei; Xiang, Xiyan; Li, Xiaoning; Zhang, Zhichao; Sun, Liankun

doi:10.1016/j.canlet.2012.04.009

Cited by 52 publications

(57 citation statements)

References 40 publications

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“…Gossypol Triggers an ER Stress Response and Induces NOXA in an ATF4/ATF3-dependent Manner-We and others have found previously that many putative BH3 mimetics trigger the ISR, which involves the transcription factors ATF4 and ATF3 leading to the induction of NOXA (25,29,30). We also established that one such BH3 mimetic, S1, triggers the ISR pathway through the canonical ER stress, which included activation of the eIF2␣ kinase, PERK (30).…”

Section: Noxa Is Required For Gossypol-mediated Sensitization Tosupporting

confidence: 54%

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Gossypol Increases Expression of the Pro-apoptotic BH3-only Protein NOXA through a Novel Mechanism Involving Phospholipase A2, Cytoplasmic Calcium, and Endoplasmic Reticulum Stress

Soderquist¹,

Danilov

Eastman

2014

Journal of Biological Chemistry

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Background:The mechanism through which gossypol mediates anti-cancer activity is poorly understood. Results: Gossypol rapidly activates phospholipase A2, increases cytoplasmic calcium, endoplasmic reticulum stress, and NOXA, and sensitizes cells to apoptosis. Conclusion: Phospholipase A2 is a novel target of gossypol. Significance: This pathway can explain many reported activities of gossypol including sensitization to the BCL2 inhibitor,

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Section: Noxa Is Required For Gossypol-mediated Sensitization Tosupporting

confidence: 54%

“…Specifically, AA or increased calcium can induce oxidative stress, autophagy, and JNK activity (58 -63). In addition, calcium signaling has been shown to increase DR5 expression (29).…”

Section: Discussionmentioning

confidence: 99%

Gossypol Increases Expression of the Pro-apoptotic BH3-only Protein NOXA through a Novel Mechanism Involving Phospholipase A2, Cytoplasmic Calcium, and Endoplasmic Reticulum Stress

Soderquist¹,

Danilov

Eastman

2014

Journal of Biological Chemistry

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“…S1 increases reactive oxygen species, resulting in initiation of endoplasmic reticulum (ER) stress [56]. S1-mediated death is in part because of autophagy through ER stress and disruption of Beclin 1/BCL-2 interaction [57].…”

Section: Wehi-539 [48]mentioning

confidence: 99%

BH3 mimetics: Their action and efficacy in cancer chemotherapy

Nakajima¹,

Tanaka²

2016

Integr Cancer Sci Therap

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Evading apoptosis is a hallmark of cancer, and anti-apoptotic BCL-2 family proteins are frequently highly expressed in cancers. In cancer cells, aberrant DNA replication invokes replication-associated DNA damage signaling in cancer cells; however, DNA damage-induced apoptotic signals are masked by such apoptosis evasion systems. Therefore, it is considered that targeting of apoptosis is efficient for cancer cell-selective therapeutic methods. BCL-2 family proteins are critical regulators of mitochondrion-mediated apoptosis, and 'BH3-only' subfamily proteins induce apoptosis by binding to anti-apoptotic BCL-2 family proteins via their BH3 domain. BH3 mimetics are small molecules that mimic BH3-proteins by binding to anti-apoptotic BCL-2 family proteins. To date, more than 20 compounds have been identified, and their effects in cancer therapy have been analyzed. In this review, their efficacy in cancer chemotherapy will be discussed.

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“…Previous reports have suggested that autophagy can be induced by S1 (20). Therefore, we used indirect fluorescence technology to detect the activation of autophagy.…”

Section: S1 Treatment Activates Autophagy In Skov3/ddp Cellsmentioning

confidence: 99%

“…S1 has been proven to induce apoptosis of liver cancer cells and breast cancer cells via the mitochondrial pathway by interfering with the interactions between Bcl-2/Bax and Mcl-1/Bak, and thus exhibits antitumor activity (18,19). Moreover, S1 was shown to induce autophagy and ER stress in human glioma cells (20).…”

Section: Introductionmentioning

confidence: 99%

The BH3 mimetic S1 induces endoplasmic reticulum stress-associated apoptosis in cisplatin-resistant human ovarian cancer cells although it activates autophagy

Liu

Sun

et al. 2013

Oncology Reports

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Abstract. SKOV3/DDP human ovarian cancer cells have been shown to be resistant to cisplatin. Although the BH3 mimetic S1 induces cell death in several types of tumor cells, it is unclear whether it induces death in drug-resistant cells. Herein, we found that S1 induced endoplasmic reticulum (ER) stress-associated apoptosis in both SKOV3 and SKOV3/DDP cells. S1 activated autophagy at early time points in SKOV3/ DDP cells, and inhibition of autophagy increased ER stressassociated apoptosis. Collectively, our data indicate that autophagy plays a protective role, but it cannot protect against S1-induced cell death in cisplatin-resistant SKOV3/DDP cells.

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The BH3 mimetic S1 induces autophagy through ER stress and disruption of Bcl-2/Beclin 1 interaction in human glioma U251 cells

Cited by 52 publications

References 40 publications

Gossypol Increases Expression of the Pro-apoptotic BH3-only Protein NOXA through a Novel Mechanism Involving Phospholipase A2, Cytoplasmic Calcium, and Endoplasmic Reticulum Stress

Gossypol Increases Expression of the Pro-apoptotic BH3-only Protein NOXA through a Novel Mechanism Involving Phospholipase A2, Cytoplasmic Calcium, and Endoplasmic Reticulum Stress

BH3 mimetics: Their action and efficacy in cancer chemotherapy

The BH3 mimetic S1 induces endoplasmic reticulum stress-associated apoptosis in cisplatin-resistant human ovarian cancer cells although it activates autophagy

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