Resveratrol and siRNA in combination reduces Hsp27 expression and induces caspase-3 activity in human glioblastoma cells

Abstract

GBM cells can easily gain resistance to conventional therapy, and therefore treatment of glioblastoma multiforme (GBM) is difficult. One of the hallmark proteins known to be responsible for this resistance is heat shock protein 27 (Hsp27) which has a key role in the cell survival. Resveratrol, a natural compound, exhibits antitumor effects against GBM, but there are no reports regarding its effect on Hsp27 expression in gliomas. The aim of the present study was to asses the effect of resveratrol on Hsp27 expression and apoptosis in non-transfected and transfected U-87 MG human glioblastoma cells. In order to block the Hsp27 expression, siRNA transfection was performed. Non-transfected and transfected cells were treated with either 10 or 15 μM resveratrol. The effects of resveratrol were compared with quercetin, a well-known Hsp27 inhibitor. Resveratrol was found to induce apoptosis more effectively than quercetin. Our data showed that resveratrol induces dose-and time-dependent cell death. We also determined that silencing of Hsp27 with siRNA makes the cells more vulnerable to apoptosis upon resveratrol treatment. The highest effect was observed in the 15 μM resveratrol and 25 nM siRNA combination group (suppressed Hsp27 expression by 93.4% and induced apoptosis by 101.2%). This study is the first report showing that resveratrol reduces Hsp27 levels, and siRNA-mediated Hsp27 silencing enhances the therapeutic effects of resveratrol in glioma cells. Our results suggest that resveratrol administration in combination with Hsp27 silencing has a potential to be used as a candidate for GBM treatment.

Brain Tumor-Derived Extracellular Vesicles as Carriers of Disease Markers: Molecular Chaperones and MicroRNAs

“…Hsp27 is an important regulator of F-actin polymerization and it was shown that p38MAPK activation, followed by Hsp27 phosphorylation, was required for Phorbol 12-myristate 13-acetate (PMA)-induced migration of glioblastoma cells, suggesting that this chaperone is a potential target of negative chaperonotherapy to inhibit cancer invasion and progression [211]. This hypothesis was further supported by findings showing that Hsp27 downregulation synergizes the anticancer effects of different drugs and treatments, reducing GBM cell proliferation and promoting caspase 3-mediated apoptosis [212][213][214].…”

Drug Delivery Systems in the Development of Novel Strategies for Glioblastoma Treatment

“…Since GBM cells are resistant to anti-tumor drugs, the use of siRNA in combination with chemotherapy could be beneficial to enhancing the treatment efficiency [161]. For example, the combination of resveratrol (RES) and heat shock protein 27-knockdown using siRNA (Hsp27) was tested to treat the disease [162]. Hsp27 is a tumor-promoting factor in GBM implicated in ECM remodeling and cell survival.…”

Progress in Natural Compounds/siRNA Co-delivery Employing Nanovehicles for Cancer Therapy

“…Heat shock proteins (HSPs) are involved in malignancy and HSP27 is one of these proteins. Overexpression of HSP27 causes metastasis of cancer cells via induction of epithelial–mesenchymal transition. , A combination of resveratrol and siRNA–HSP27 significantly inhibited the proliferation and migration of glioblastoma cells via down-regulation of HSP27 and activation of caspase-3, which, in turn, causes apoptosis of the cancer cells …”

“…387,388 A combination of resveratrol and siRNA−HSP27 significantly inhibited the proliferation and migration of glioblastoma cells via down-regulation of HSP27 and activation of caspase-3, which, in turn, causes apoptosis of the cancer cells. 389 The use of nanoplatforms for co-delivery of Res and siRNA enhances their antitumor activity. Over the past decades, electrospun fibers have been considered ideal candidates for drug delivery because of their potential in acting as platforms for sustained drug release.…”