Recombinant heat shock protein 27 (HSP27/HSPB1) protects against cadmium-induced oxidative stress and toxicity in human cervical cancer cells

Abstract

Cadmium (Cd) is a carcinogen with several well-described toxicological effects in humans, but its molecular mechanisms are still not fully understood. Overexpression of heat shock protein 27 (HSP27/HSPB1)-a multifunctional protein chaperone-has been shown to protect cells from oxidative damage and apoptosis triggered by Cd exposure. The aims of this work were to investigate the potential use of extracellular recombinant HSP27 to prevent/counteract Cd-induced cellular toxicity and to evaluate if peroxynitrite was involved in the development of Cd-induced toxicity. Here, we report that the harmful effects of Cd correlated with changes in oxidative stress markers: upregulation of reactive oxygen species, reduction in nitric oxide (NO) bioavailability, increment in lipid peroxidation, peroxynitrite (PN), and protein nitration; intracellular HSP27 was reduced. Treatments with Cd (100 μM) for 24 h or with the peroxynitrite donor, SIN-1, decreased HSP27 levels (~50%), suggesting that PN formation is responsible for the reduction of HSP27. Pre-treatments of the cells either with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) (a pharmacological inhibitor of NO synthase) or with recombinant HSP27 (rHSP27) attenuated the disruption of the cellular metabolism induced by Cd, increasing in a 55 and 52%, respectively, the cell viability measured by CCK-8. Cd induced necrotic cell death pathways, although apoptosis was also activated; pre-treatment with L-NAME or rHSP27 mitigated cell death. Our findings show for the first time a direct relationship between Cd-induced toxicity and PN production and a role for rHSP27 as a potential therapeutic agent that may counteract Cd toxicity.

Allicin suppresses the migration and invasion in cervical cancer cells mainly by inhibiting NRF2

“…It is estimated that approximately over 500,000 new cases are reported each year (1). Previous studies have indicated that human papilloma virus (HPV) infection is the major cause of cervical cancer (2,3). Undoubtedly, long term exposure to oxidative stress by cervical epithelial tissues will lead to the persistent, chronic viral infections, thereby causing genetic rearrangements and genomic instability due to the integration of the viral genome (4,5).…”

Mutation at Different Sites of Metal Transporter Gene OsNramp5 Affects Cd Accumulation and Related Agronomic Traits in Rice (Oryza sativa L.)

“…At present, it is the staple food of more than half the world’s population (Wang et al, 2013). Cd is carcinogenic to humans and has been classified as a Class I carcinogen by the International Agency for Research on Cancer (Broerse et al, 2012; Alvarez-Olmedo et al, 2017). Cd is mainly absorbed from the soil through the roots and reaches the vascular bundle through the two plant transport pathways—the symplast and the apoplast—by which it is then transported to the stems and leaves and later migrates to the grains, finally accumulating in the human body through the food chain, thereby causing serious harm to human health (Yao et al, 2003; Seregin and Kozhevnikova, 2008; Yoneyama et al, 2015).…”

Expression of Heat Shock Protein-27 (Hsp27) and P38MAPK in Esophageal Squamous Cell Carcinoma

“…Heat shock protein 27 (Hsp27) is a member of the heat shock protein family which has been linked to tumor progression and, most interestingly, to chemotherapy resistance in cancer patients. There is evidence showing a role for Hsp27 in the balance between tumor dormancy and tumor progression, mediated by tumor-vascular interactions [ 4 ]. Hsp27 function is associated with deleterious outcomes in cancer and is associated with the development of drug resistance [ 5 ].…”