The heat shock protein 70 inhibitor VER155008 suppresses the expression of HSP27, HOP and HSP90β and the androgen receptor, induces apoptosis, and attenuates prostate cancer cell growth

Abstract

Heat shock proteins (HSPs) are molecular chaperones that play a pivotal role in correct folding, stabilization and intracellular transport of many client proteins including those involved in oncogenesis. HSP70, which is frequently overexpressed in prostate cancer (PCa), has been shown to critically contribute to tumor cell survival, and might therefore represent a potential therapeutic target. We treated both the androgen receptor (AR)‐positive LNCaP and the AR‐negative PC‐3 cell lines with the pharmacologic HSP70 inhibitor VER155008. Although we observed antiproliferative effects and induction of apoptosis upon HSP70 inhibition, the apoptotic effect was more pronounced in AR‐positive LNCaP cells. In addition, VER155008 treatment induced G1 cell cycle arrest in LNCaP cells and decreased AR expression. Further analysis of the HSP system by Western blot analysis revealed that expression of HSP27, HOP and HSP90β was significantly inhibited by VER155008 treatment, whereas the HSP40, HSP60, and HSP90α expression remained unchanged. Taken together, VER155008 might serve as a novel therapeutic option in PCa patients independent of the AR expression status.

Thermal stress involved in TRPV2 promotes tumorigenesis through the pathway of PI3K/Akt/mTOR in esophageal squamous cell carcinoma

“…5a, c, e-f). Previous works had reported that these two HSP proteins are involved in the progression of multiple types of cancers [33][34][35]. HSP70 and HSP27 may also play a role in the tumorigenesis of ESCC following the overactivation of TRPV2.…”

Molecular mechanisms in chaperonopathies: clues to understanding the histopathological abnormalities and developing novel therapies

“…negative chaperonotherapy. In this regard, current research aims at finding and standardizing compounds and delivery means targeting as specifically as possible the pathogenic chaperone [82][83][84][85][86]. If the chaperonopathy is by defect, positive chaperonotherapy is indicated, consisting in chaperone gene or protein replacement, or the use of manufactured chaperoning structures [87][88][89]; or chaperone-protein functional boosting with chemical compounds, namely chemical chaperones similar to those utilized for restoring enzymatic activity in genetic enzymopathies [82,[90][91][92][93].…”

Are IgG antibodies to heat shock proteins HSP27 and HSP60 useful markers in endometrial cancer and cervical cancer?

“…On the other hand, a marked and rapid overexpression of most HSPs in response to cellular damage is found, with cancer cells having been found to over-stimulate the synthesis of heat shock proteins [15]. This may be of fundamental importance in the pathogenesis and progression of cancerthe significant role of heat shock proteins as a therapeutic target in cancer has been demonstrated [16,17] but, on the other hand, they are also associated with drug resistance in cancer [18].…”