Co-culture with NK-92MI cells enhanced the anti-cancer effect of bee venom on NSCLC cells by inactivation of NF-κB

Abstract

In the present study we experimented on a multimodal therapeutic approach, such as combining chemotherapy agent (Bee venom) with cellular (NK-92MI) immunotherapy. Previously bee venom has been found to show anti-cancer effect in various cancer cell lines. In lung cancer cells bee venom showed an IC(50) value of 3 μg/ml in both cell lines. The co-culture of NK-92MI cell lines with lung cancer cells also show a decrease in viability upto 50 % at 48 h time point. Hence we used bee venom treated NK-92MI cells to co-culture with NSCLC cells and found that there is a further decrease in cell viability upto 70 and 75 % in A549 and NCI-H460 cell lines respectively. We further investigated the expression of various apoptotic and anti-apoptotic proteins and found that Bax, cleaved caspase-3 and -8 were increasing where as Bcl-2 and cIAP-2 was decreasing. The expression of various death receptor proteins like DR3, DR6 and Fas was also increasing. Concomitantly the expression of various death receptor ligands (TNFalpha, Apo3L and FasL) was also increasing of NK-92MI cells after co-culture. Further the DNA binding activity and luciferase activity of NF-κB was also inhibited after co-culture with bee venom treated NK-92MI cell lines. The knock down of death receptors with si-RNA has reversed the decrease in cell viability and NF-κB activity after co-culture with bee venom treated NK-92MI cells. Thus this new approach can enhance the anti-cancer effect of bee venom at a much lower concentration.

Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy

“…Further, the DNA binding activity and luciferase activity of NF-κB was also inhibited after co-culture with BV treated NK-92MI cell lines. The knock down of death receptors with siRNA was observed to reverse the decrease in cell viability and NF-κB activity after co-culture with BV treated NK-92MI cells [50]. Similar effects of death receptor mediated BV activity was observed by Jo et al [41], where they suggested that BV and MEL induces apoptotic cell death in SKOV3 and PA-1 ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway.…”

Synergistic Effect of Natural Killer Cells and Bee Venom on Inhibition of NCI-H157 Cell Growth

“…Apoptosis occurs through two mechanisms that are expressed in the mitochondria 35) and from the cell surface 30) . In the cell surface, receptors such as perform a major role in resistance to various treatment applied [36][37][38] . In other words, the regulation of NF-κ B can be a key to the treatment in the cancer cells.…”

“…In korean medicine, the studies of herb medication and pharmacopuncture for inducing apoptosis have been actively conducted 13,[16][17][18] , and lately, there are many studies that BV has the effect of regulation of NF-κ B 24,[26][27][28][29][30][31]35,38,39) .…”

Biotoxins for Cancer Therapy

“…BV induces apoptotic cell death through several cancer cell death mechanisms, among them the activation of PLA2 by melittin is the critical mechanism for the anti-cancer activity of BV. The conjugation of cell lytic peptide (melittin) with hormone receptors and gene therapy carrying melittin can be useful as a novel targeted therapy for some types of cancer (Orsolic, 2012;Kollipara et al, 2014).…”