Abstract
Albendazole (ABZ) has been reported to display anti-tumoral actions against various maliganncies, but possible impact of ABZ on gastric cancer has not been deciphered. As aberrant phosphorylation of STAT3 and STAT5 proteins can regulate the growth and progression of gastric cancer, we postulated that ABZ may interrupt the activation of these oncogenic transcription factors. We found that ABZ exposure abrogated STAT3/5 activation, inhibited phosphorylation of Janus-activated kinases 1/2 and Src and enhanced the levels of SHP-1 protein. Silencing of SHP-1 gene by small interfering RNA (siRNA) reversed the ABZ-promoted attenuation of STAT3 as well as STAT5 activation and cellular apoptosis. In addition, these effects were noted to be driven by an augmented levels of reactive oxygen species caused by drug-induced GSH/GSSG imbalance. Thus, the data indicates that ABZ can modulate the activation of STAT3 and STAT5 by pleiotropic mechanisms in gastric cancer cells.
Highlights
IntroductionPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
The influence of ABZ on gastric cancer cells and the underlying mechanisms have not been evaluated previously. It was investigated whether ABZ can impact the activation of STAT3 and STAT5 pathway in gastric cancer cells and thereby exhibit pleiotropic actions on tumor progression as well as survival
Anti-STAT3, anti-PTPε, anti-SHP-1, anti-Procaspase-3, anti-PARP, anti-Bcl-2, anti-Bcl-xL, anti-Survivin, anti-Cyclin D1, anti-COX-2, anti-β-actin antibodies, and SHP-1 small interfering RNA (siRNA) were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA)
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Various previous reports have indicated that a number of naturally derived pharmacological agents can attenuate STAT activation, which may have a great potential in the prevention and therapy of cancer [13,22,23,24,25,26]. Biomedicines 2021, 9, 362 malignancies including gastric cancer [38], targeting of STAT3/5 phosphorylation may be beneficial for gastric cancer treatment. The influence of ABZ on gastric cancer cells and the underlying mechanisms have not been evaluated previously. In this study, it was investigated whether ABZ can impact the activation of STAT3 and STAT5 pathway in gastric cancer cells and thereby exhibit pleiotropic actions on tumor progression as well as survival
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