Conjugation of bisphosphonates with scorpion venom enhanced apoptotic activities in pancreatic cancer cells

Abstract

BackgroundIn recent times, prevalence and the incidence of pancreatic cancer (PC) have increased exponentially. Among of the major issues of PC are the asymptotic manifestation that delays diagnosis, and scarcity of therapeutic means. MethodologyTo provide an effective therapeutic approach, current study was executed, in which an optimized alendronate sodium (ALS) and scorpion venom (SV) nanoconjugate (ALS-SV nanoconjugate) was selected via experimental design applying size and zeta potential as the selected factors. Additionally, efficacy against PANC1 cells was determined by analysis of IC50, cell cycle, annexin V staining, Bcl-2, Bax, p53, etc. ResultsThe particle size of the optimized nanoconjugate was found to be 28.4{+/-} 1.2 nm and the zeta potential to be +26.2{+/-} 0.8 mV. The cytotoxicity in terms of IC50 ALS-SV nanoconjugate was found better (2.73 {+/-} 0.2 {micro}g/mL) than ALS alone (22.3 {+/-} 0.2 {micro}g/mL) and SV alone (6.23 {+/-} 0.4 {micro}g/mL). Besides, outcomes of cell cycle analysis exhibited maximum efficacy for nanoconjugate in the G2-M phase. Annexin V staining, Bax, Bcl-2, p53, and caspase 3 estimation also showed superior apoptotic activity for ALS-SV nanoconjugate. However, as compared to ALS alone and SV alone, nanoconjugate showed elevated expression levels of TNF-. The apoptotic activity was enhanced by the ALS-SV nanoconjugate as confirmed by MMP analysis. ConclusionAccordingly, the current study revealed an enhancement in the anti-PC effects of the ALS-SV nanoconjugate that is considered as a novel approach against PC.