The Natural Compound Cantharidin Induces Cancer Cell Death through Inhibition of Heat Shock Protein 70 (HSP70) and Bcl-2-associated Athanogene Domain 3 (BAG3) Expression by Blocking Heat Shock Factor 1 (HSF1) Binding to Promoters

Abstract

Background: HSF1 is a transcription factor that enhances cancer formation and progression. Results: Cantharidin inhibited the binding of HSF1 to the HSP70 promoter and subsequently blocked HSF1-dependent HSP70 expression. Conclusion:The HSF1-dependent expression of HSP70 and BAG3 is inhibited by cantharidin, causing the down-regulation of antiapoptotic BCL-2 family proteins, especially MCL-1. Significance: This information provides a new target molecule and pathway of cantharidin.

HSF1 Protects Neurons through a Novel Trimerization- and HSP-Independent Mechanism

“…This cooperation is likely mediated through a direct interaction between HSF1 and SIRT1 in the nucleus of neurons. SIRT1 has been shown previously to protect neurons in both cell culture and in in vivo models of neurodegenerative disease (Qin et al, 2006;Kim et al, 2007;Pfister et al, 2008;Tang and Chua, 2008;Jeong et al, 2012;Jiang et al, 2011). Interestingly, we have found previously that the catalytic activity of SIRT1 is not needed for neuroprotection by SIRT1 (Pfister et al, 2008).…”

Tyrosine kinase inhibitor tyrphostin AG490 triggers both apoptosis and autophagy by reducing HSF1 and Mcl-1 in PEL cells

“…Mcl-1 is a Bcl-2 family member that negatively regulates both apoptosis and autophagy [31,32]. This molecule has been previously reported to be reduced by AG490 treatment [33,34] and more recent studies have reported that also HSF1 can influence Mcl-1 expression [35]. However, a link between AG490, HSF1 and Mcl-1 molecules was not previously reported.…”

Molecular docking and dynamic simulation evaluation of Rohinitib — Cantharidin based novel HSF1 inhibitors for cancer therapy

“…The binding of active HSF1 to HSE induces the transcription of Hsp40, Hsp70, Hsp90, BAG3 and other chaperones, thus, initiating the cytoprotective molecular mechanisms (Fig. 1) [4,5,6,8].…”

“…The cancerous cells have been associated with high level of DNA damage, reactive oxygen species and aneuploidy and thus require stress response pathways for their survival [8,9].…”