In view of the emergence of multidrug-resistant
cancer cells, there is a need for therapeutic alternatives. Keeping this in mind, the present study was aimed at evaluating the synergism between
nisin (an
antimicrobial peptide) and
doxorubicin (DOX) against DMBA-induced skin
carcinogenesis. The possible tumoricidal activity of the combination was evaluated in terms of animal bioassay observations, changes in hisotological architecture of skin tissues, in situ apoptosis assay (TUNEL assay) and in terms of
oxidant and
antioxidant status of the skin tissues. In vivo additive effect of the combination was evidenced by larger decreases in mean tumour burden and tumour volume in mice treated with the combination than those treated with the drugs alone. Histological observations indicated that
nisin-DOX
therapy causes
chromatin condensation and marginalisation of nuclear material in skin tissues of treated mice which correlated well with the results of TUNEL assay wherein a marked increase in the rate of apoptosis was revealed in tissues treated with the combination. A slightly increased oxidative stress in response to the adjunct
therapy as compared to dox-alone-treated group was revealed by levels of lipid peroxidation (LPO) and
nitrite generation in skin tissue-treated mice. An almost similar marginal enhancement in
superoxide dismutase levels corresponding with a decrease in
catalase activity could also be observed in nisin + DOX-treated groups as compared to
nisin and dox-alone-treated groups. These results point towards the possible use of
nisin as an adjunct to
doxorubicin may help in developing alternate strategies to combat currently developing drug resistance in
cancer cells.