Hsp60 chaperonopathies and chaperonotherapy: targets and agents

The dissociation of the Hsp60/pro-Caspase-3 complex by bis(pyridyl)oxadiazole copper complex ( CubipyOXA ) leads to cell death in NCI-H292 cancer cells

“…Along this line of thought, inhibition of certain Hsps known to be involved in carcinogenesis has been proposed as a potential anti-cancer treatment strategy worth testing [42][43][44]35]. Furthermore, monitoring the levels of Hsps can be a useful way of following up the response to therapy [6].…”

“…Hsp60 has been implicated in carcinogenesis via its interaction with components of the Caspase cascade that leads to apoptosis. However, opinions about the role of this chaperone in carcinogenesis, and in apoptosis in particular, differ and it is not yet clear when and how Hsp60 is pro-apoptotic (i.e., it acts as an anti-cancer factor) or the contrary, namely it works in favor of the tumor by interfering with apoptosis [5][6][7][8][9][10].…”

“…Our recent studies have shown that the induction of stress on cancer cells affects the Hsp60 levels [6,11,12] and it is known that this chaperone plays a crucial role in apoptosis. Furthermore, we found that Hsp60 interacts with Pro-Caspase-3 (pC3) in the mucoepidermoid carcinoma cell line NCI-H292 and this association persists after the induction of oxidative stress [5].…”

Doxorubicin anti-tumor mechanisms include Hsp60 post-translational modifications leading to the Hsp60/p53 complex dissociation and instauration of replicative senescence

“…High doses of doxorubicin (640 and 1280 nM) decreased H292 cell viability inducing apoptotic cell death, as suggested by flow cytometry analysis (see later). On the basis of these results, three subapoptotic doses (20,40, and 80 nM) were chosen to evaluate doxorubicin effect after 5 days of treatment. Morphological changes were already visible starting at 20 nM of doxorubicin.…”

“…The mitochondrial chaperonin Hsp60 also named HSPD1 [17] was found in multiple subcellular sites and function in the folding and intracellular trafficking of many proteins [18,19]. Hsp60 has been found elevated in a large number of human carcinomas, which opens novel perspectives for cancer diagnosis and therapy targeting Hsp60 [20,21]. The chaperonin can activate the immune system [22] and can have both, pro-survival and pro-death functions, depending on tissue, cell type, and apoptosis inducers [23].…”