Hsp90 inhibitors, GA and 17AAG, lead to ER stress-induced apoptosis in rat histiocytoma

Taiyab, Aftab; Sreedhar, Amere Subbarao; Rao, Ch. Mohan

doi:10.1016/j.bcp.2009.04.001

Cited by 73 publications

(48 citation statements)

References 36 publications

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“…ER Ca 2þ stores are depleted by euplotin C through activated RyRs (Cervia et al 2006), by paclitaxel through formation of Bax dimers in the ER (Liao et al 2008), and by epigallocatechin gallate through inhibited protein processing at the level of glucosidase II (Magyar et al 2009) and GRP78/BiP (Ermakova et al 2006). Ca 2þ depletion and ER stress are also induced by cisplatin (Nawrocki et al 2005), dehydrocostuslactone Hung et al 2010), honokiol ), diaryl-and triarylmethanes (Abdelrahim et al 2006, inhibitors of heat shock protein 90 (Taiyab et al 2009), n-3 long-chain polyunsaturated fatty acids (Jakobsen et al 2008), rhein ), cardiotoxin III (Chien et al 2008), homoharringtonine (Jie et al 2007), berberine (Lin et al 2007b), diindolylmethane (Savino et al 2006), the multi-kinase inhibitor sorafenib (Rahmani et al 2007), the p210 bcr-abl tyrosine-kinase inhibitor STI571 (Pattacini et al 2004), parthenolide , photodynamic therapy with tetra-S-glycosylated porphyrin (Thompson et al 2008), and by many other drugs. Edelfosine leads to Bax/ Bak-mediated ER Ca 2þ depletion and apoptosis, without inducing a UPR (Nieto-Miguel et al 2007).…”

Section: Anticancer Drugsmentioning

confidence: 99%

Endoplasmic-Reticulum Calcium Depletion and Disease

Mekahli¹,

Bultynck²,

Parys³

et al. 2011

Cold Spring Harbor Perspectives in Biology

394

308

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Section: Anticancer Drugsmentioning

confidence: 99%

Endoplasmic-Reticulum Calcium Depletion and Disease

Mekahli¹,

Bultynck²,

Parys³

et al. 2011

Cold Spring Harbor Perspectives in Biology

394

308

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“…Several established compounds interfering with protein metabolism and turnover can induce UPR activation. Here, proteasome inhibitors like brotezomib [147], heat shock protein inhibitors like geldanamycin (17-AAG) [148] or protein deacetylase inhibitors like panobinostat [149,150,151] can rapidly induce ER stress-mediated apoptosis in cancer cells.…”

Section: Novel Compounds Enhancing Cell Death Responsesmentioning

confidence: 99%

Apoptosis-Modulating Drugs for Improved Cancer Therapy

Ocker

Höpfner

2012

Eur Surg Res

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Resistance to cell death induction has been recognized as a hallmark of cancer. Increasing understanding of the underlying molecular events regulating different cell death mechanisms like apoptosis, endoplasmic reticulum stress, autophagy, necroptosis and others has opened new possibilities for targeted interference with these pathways. While conventional chemotherapeutic agents usually inhibit cell cycle progression, DNA replication or mitosis execution, novel agents like small molecule kinase inhibitors also target survival-related kinases and signaling pathways and contribute to overcome resistance to chemotherapy and apoptosis. Additionally, antibodies targeting cellular death receptors have been described to specifically target tumor cells only. This review briefly highlights the pathways involved in (apoptotic) cell death and summarizes the current state of development of specific modulators of cell death and how they can help to improve the tolerability of chemotherapy regimens and increase survival rates in patients with advanced cancer diseases.

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“…So the selective inhibition of Hsp90 consequently inhibits the aberrant survival signaling pathway, which can induce apoptosis in cancer. The discovery of natural products that display anti-tumor activity by inhibiting Hsp90 function brought about a promising new class of pharmaceuticals [4]. Hsp90 inhibitors have already shown promising anti-tumor activity in preclinical model systems [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Heat shock protein 90 mediates the apoptosis and autophage in nicotinic-mycoepoxydiene-treated HeLa cells

Sun¹,

Xiao²,

Chen³

et al. 2015

ABBS

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Heat shock protein 90 (Hsp90) is a fascinating target for cancer therapy due to its significant role in the crossroad of multiple signaling pathways associated with cell proliferation and regulation. Hsp90 inhibitors have the potential to be developed into anti-cancer drugs. Here, we identified nicotinicmycoepoxydiene (NMD), a structurally novel compound as Hsp90 inhibitor to perform the antitumor activity. The compound selectively bound to the Hsp90 N-terminal domain, and degraded the Hsp90 client protein Akt. The degradation of Akt detained Bad in non-phosphorylation form. NMD-associated apoptosis was characterized by the formation of fragmented nuclei, poly(ADPribose) polymerase cleavage, cytochrome c release, caspase-3 activation, and the increased proportion of sub-G1 phase cells. Interestingly, the apoptosis was accompanied with autophagy, by exhibiting the increased expression of LC-3 and the decrease of lysosome pH value. Our findings provide a novel cellular mechanism by which Hsp90 inhibitor adjusts cell apoptosis and autophagy in vitro, suggesting that NMD not only has a potential to be developed into a novel anti-tumor pharmaceutical, but also exhibits a new mechanism in regulating cancer cell apoptosis and autophagy via Hsp90 inhibition.

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Hsp90 inhibitors, GA and 17AAG, lead to ER stress-induced apoptosis in rat histiocytoma

Cited by 73 publications

References 36 publications

Endoplasmic-Reticulum Calcium Depletion and Disease

Endoplasmic-Reticulum Calcium Depletion and Disease

Apoptosis-Modulating Drugs for Improved Cancer Therapy

Heat shock protein 90 mediates the apoptosis and autophage in nicotinic-mycoepoxydiene-treated HeLa cells

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