A novel Bcl-X<sub>L</sub>inhibitor Z36 that induces autophagic cell death in Hela cells

Lin, Jian; Zheng, Zhibin; Li, Yanjun; Yu, Wenyu; Zhong, Wu; Tian, Songhai; Zhao, Fang; Ren, Xiaobai; Xiao, Junhai; Wang, Nan; Liu, Siyang; Wang, Lili; Sheng, Fugeng; Chen, Yingyu; Jin, Changwen; Li, Song; Xia, Bin

doi:10.4161/auto.5.3.7888

Cited by 33 publications

(33 citation statements)

References 34 publications

(48 reference statements)

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“…[24][25][26][27][28][29][30][31] In contrast to classical or canonical autophagy, noncanonical autophagy is a process that is neither blocked by the knockdown of BECN1 or its binding partner PIK3C3, nor inhibited by pharmacological inhibitors wortmannin (WM) or 3-methyladenine (3-MA), which interfere with the activity of the PtdIns3K. [24][25][26][27][28][29][30][31] The autophagy involved in vacuole biogenesis in plants also appears to be noncanonical, as it is also resistant to PtdIns3K inhibitors. 25 A better understanding of the role of noncanonical autophagy calls for further investigations to elucidate the molecular mechanism by which autophagy occurs bypassing BECN1 and PIK3C3.…”

Section: Bag3-dependent Noncanonical Autophagy Induced By Proteasome mentioning

confidence: 99%

BAG3-dependent noncanonical autophagy induced by proteasome inhibition in HepG2 cells

Liu

Zong

et al. 2013

Autophagy

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Section: Bag3-dependent Noncanonical Autophagy Induced By Proteasome mentioning

confidence: 99%

BAG3-dependent noncanonical autophagy induced by proteasome inhibition in HepG2 cells

Liu

Zong

et al. 2013

Autophagy

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“…Small-molecule inhibitors of antiapoptotic Bcl-2 family members have shown promise in overcoming chemo/ radioresistance in various tumor models including prostate cancer (5,6). (À)-Gossypol (Supplementary Fig.…”

Section: Introductionmentioning

confidence: 99%

Sorafenib Sensitizes (−)-Gossypol-Induced Growth Suppression in Androgen-Independent Prostate Cancer Cells via Mcl-1 Inhibition and Bak Activation

Lian

Dai

et al. 2012

Molecular Cancer Therapeutics

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The natural BH3-mimetic (À)-gossypol shows promising efficacy in ongoing phase II/III clinical trials for human prostate cancer. Here, we show for the first time, that treatment with (À)-gossypol and multikinase inhibitor sorafenib synergistically suppresses the growth of androgen-independent prostate cancer cells (AI-PC) in vitro and in vivo. Our data suggest that sorafenib attenuates (À)-gossypol-induced Mcl-1 upregulation in AI-PCs. In this way, it serves as a potent chemosensitizer to affect cell death. Interestingly, (À)-gossypol and sorafenib induce cell death via two distinct pathways among different AI-PCs; DU145 cells via apoptosis and PC-3 via autophagy. The appointed death pathway may depend on the level of proapoptotic protein Bak, although the level of antiapoptotic protein Bcl-2 plays some role in it. DU145 cells with high Bak level prefer apoptosis induction, whereas PC-3 cells with low Bak prefer the induction of autophagy. Furthermore, inhibiting nondominant death pathways, that is, autophagy in DU145 and apoptosis in PC-3, enhances cell killing by (À)-gossypol/sorafenib combination therapy. Ultimately, our data expose a new action for sorafenib as an enhancer of (À)-gossypol-induced cell growth suppression and reveal a novel cell death mode by Bak activation manners in AI-PCs. These new insights may facilitate the rational design of clinical trials by selecting patients most likely to benefit from the Bcl-2-targeted molecular therapy. Mol Cancer Ther; 11(2); 416-26. Ó2011 AACR.

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“…Recent studies identify crucial functions of BNIP3 and BNIP3L in hypoxia-induced autophagy and indicate that hypoxia impacts cell survival. BNIP3 family disrupts the Bcl-2/Beclin1 complex and induces autophagy, especially when Bcl-2 or Bcl-X L is weakly expressed [39, 40]. In our study, BNIP3 was highly expressed under hypoxia (FC >7), while Bcl-2, Bcl-K L and Beclin1 were downregulated.…”

Section: Discussionmentioning

confidence: 48%

Adipose-derived mesenchymal stem cells from patients with atherosclerotic renovascular disease have increased DNA damage and reduced angiogenesis that can be modified by hypoxia

et al. 2016

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BackgroundAdipose-derived MSC (AMSCs) possess angiogenic and immunomodulatory properties that may modulate kidney regeneration. Whether these properties are retained in older patients with atherosclerotic vascular disease is poorly understood. Hypoxic conditions are known to modify properties and growth characteristics of AMSCs. We tested the hypothesis that AMSCs from older patients with atherosclerotic renovascular disease (RVD) differ from normal kidney donors, and whether hypoxia changes their functional and molecular properties to promote angiogenesis.MethodsAMSCs from 11 patients with RVD (mean age =74.5 years) and 10 healthy kidney donors (mean age = 51.2 years) were cultured under normoxia (20 % O2) and hypoxia (1 % O2) for 3–4 days until they reached 80 % confluency. We analyzed expression of genes and microRNAs using RNA sequencing and real-time quantitative rt-PCR. Protein expression of selected angiogenic factors (VEGF, IGF, HGF and EGF) were quantified in conditioned media using ELISAs. Apoptosis was tested using Annexin IV staining.ResultsNormoxic AMSC from RVD patients grew normally, but exhibited increased DNA damage and reduced migration. VEGF protein secretion was significantly lower in the RVD AMSCs (0.08 vs 2.4 ng/mL/ cell, p <0.05) while HGF was higher. Both trends were reversed during growth under hypoxic conditions. Hypoxia upregulated pro-angiogenic mRNAs expression in AMSCs (VEGF, FGF, STC and ANGPTL4), and downregulated expression of many miRNAs (e.g., miR-15a, miR-16, miR-93, miR-424, 126, 132, 221) except miR-210.ConclusionsThus, although AMSC from patients with RVD had increased DNA damage and reduced migration, hypoxia stimulated pro-angiogenic responses via increased expression of angiogenic genes, VEGF secretion and induction of the hypoxia-inducible miR-210, while downregulating angiogenesis-related miRNAs.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0389-x) contains supplementary material, which is available to authorized users.

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A novel Bcl-X_Linhibitor Z36 that induces autophagic cell death in Hela cells

Cited by 33 publications

References 34 publications

BAG3-dependent noncanonical autophagy induced by proteasome inhibition in HepG2 cells

BAG3-dependent noncanonical autophagy induced by proteasome inhibition in HepG2 cells

Sorafenib Sensitizes (−)-Gossypol-Induced Growth Suppression in Androgen-Independent Prostate Cancer Cells via Mcl-1 Inhibition and Bak Activation

Adipose-derived mesenchymal stem cells from patients with atherosclerotic renovascular disease have increased DNA damage and reduced angiogenesis that can be modified by hypoxia

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A novel Bcl-XLinhibitor Z36 that induces autophagic cell death in Hela cells

Cited by 33 publications

References 34 publications

BAG3-dependent noncanonical autophagy induced by proteasome inhibition in HepG2 cells

BAG3-dependent noncanonical autophagy induced by proteasome inhibition in HepG2 cells

Sorafenib Sensitizes (−)-Gossypol-Induced Growth Suppression in Androgen-Independent Prostate Cancer Cells via Mcl-1 Inhibition and Bak Activation

Adipose-derived mesenchymal stem cells from patients with atherosclerotic renovascular disease have increased DNA damage and reduced angiogenesis that can be modified by hypoxia

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A novel Bcl-X_Linhibitor Z36 that induces autophagic cell death in Hela cells