title: 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.
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Ch'ongju, Chungbuk, 361-763, Korea.
authors.forename: Pushpa Saranya
authors.initials: PS
authors.lastname: Kollipara
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Dohee
authors.initials: D
authors.lastname: Won
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Lee
authors.forename: Ha Chang
authors.initials: HC
authors.lastname: Sung
authors.forename: Hyun Sok
authors.initials: HS
authors.lastname: Chang
authors.forename: Kang Tae
authors.initials: KT
authors.lastname: Lee
authors.forename: Kang Sik
authors.initials: KS
authors.lastname: Lee
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Park
authors.forename: Min Jong
authors.initials: MJ
authors.lastname: Song
authors.forename: Ho Sueb
authors.initials: HS
authors.lastname: Song
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001514:Bee Venoms / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D018920:Coculture Techniques; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001514:Bee Venoms; D016328:NF-kappa B