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Kollipara, Pushpa Saranya,Kim, Jung Hyun,Won, Dohee,Lee, Sang Min,Sung, Ha Chang,Chang, Hyun Sok,Lee, Kang Tae,Lee, Kang Sik,Park, Mi Hee,Song, Min Jong,Song, Ho Sueb,Hong, Jin Tae 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.3
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 $3{\mu}g/ml$ 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-${\kappa}B$ 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-${\kappa}B$ 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.
Pushpa Saranya Kollipara,김정현,원도희,이상민,성하정,장현석,이강태,이강식,박미희,송민종,송호섭,홍진태 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.3
In the present study we experimented on amultimodal therapeutic approach, such as combining chemotherapyagent (Bee venom) with cellular (NK-92MI)immunotherapy. Previously bee venom has been found toshow anti-cancer effect in various cancer cell lines. In lungcancer cells bee venom showed an IC50 value of 3 lg/ml inboth cell lines. The co-culture of NK-92MI cell lines withlung cancer cells also show a decrease in viability upto50 % at 48 h time point. Hence we used bee venom treatedNK-92MI cells to co-culture with NSCLC cells and foundthat there is a further decrease in cell viability upto 70 and75 % in A549 and NCI-H460 cell lines respectively. Wefurther investigated the expression of various apoptotic andanti-apoptotic proteins and found that Bax, cleaved caspase-3 and -8 were increasing where as Bcl-2 and cIAP-2was decreasing. The expression of various death receptorproteins like DR3, DR6 and Fas was also increasing. Concomitantly the expression of various death receptorligands (TNFalpha, Apo3L and FasL) was also increasing of NK-92MI cells after co-culture. Further the DNAbinding activity and luciferase activity of NF-jB was alsoinhibited after co-culture with bee venom treated NK-92MIcell lines. The knock down of death receptors with si-RNAhas reversed the decrease in cell viability and NF-jBactivity after co-culture with bee venom treated NK-92MIcells. Thus this new approach can enhance the anti-cancereffect of bee venom at a much lower concentration.
( Jin Tae Hong ),( Pushpa Saranya Kollipara ),( Do Hee Won ),( Chul Ju Hwang ),( Yu Yeon Jung ),( Heui Seoung Yoon ),( Mi Hee Park ),( Min Jong Song ),( Ho Sueb Song ) 한국응용약물학회 2014 Biomolecules & Therapeutics(구 응용약물학회지) Vol.22 No.2
In the present study, we investigated anti-cancer effect of snake venom activated NK cells (NK-92MI) in lung cancer cell lines. Weused snake venom (4 mg/ml) treated NK-92MI cells to co-culture with lung cancer cells. There was a further decrease in cancer cellgrowth up to 65% and 70% in A549 and NCI-H460 cell lines respectively, whereas 30-40% was decreased in cancer cell growthby snake venom or NK-92MI alone treatment. We further found that the expression of various apoptotic proteins such as that Bax,and cleaved caspase-3 as well as the expression of various death receptor proteins like DR3, DR4 and Fas was also further increased. Moreover, consistent with cancer cell growth inhibition, the DNA binding activity of NF-kB was also further inhibited aftertreatment of snake venom activated NK-92MI cells. Thus, the present data showed that activated NK cells could further inhibitlung cancer cell growth.