title: Effect of nisin and doxorubicin on DMBA-induced skin carcinogenesis--a possible adjunct therapy.
abstract: 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.
authors.affiliation: Department of Biophysics, Basic Medical Sciences Block-2, Panjab University, Sector-25, Chandigarh, 160014, India. simranpreet@pu.ac.in.
authors.forename: Simran
authors.initials: S
authors.lastname: Preet
authors.affiliation: Department of Biophysics, Basic Medical Sciences Block-2, Panjab University, Sector-25, Chandigarh, 160014, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Bharati
authors.affiliation: Department of Biophysics, Basic Medical Sciences Block-2, Panjab University, Sector-25, Chandigarh, 160014, India.
authors.forename: Anshul
authors.initials: A
authors.lastname: Panjeta
authors.affiliation: Department of Microbial Technology, Panjab University, Sector-14, Chandigarh, 160014, India.
authors.forename: Rupinder
authors.initials: R
authors.lastname: Tewari
authors.affiliation: Department of Microbiology, Basic Medical Sciences Block-1, Panjab University, Sector-25, Chandigarh, 160014, India.
authors.forename: Praveen
authors.initials: P
authors.lastname: Rishi
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D063646:Carcinogenesis / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D009561:Nisin / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects; D010880:Piperidines / Q000633:toxicity; D012878:Skin Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
chemical_list: C556780:3-(2,6-bis(4-fluorophenyl)-3-methylpiperidin-4-ylideneamino)-2-thioxoimidazolidin-4-one on 7,12-dimethylbenz(a)anthracene; D000873:Anthracenes; D010880:Piperidines; D009561:Nisin; D004317:Doxorubicin
keywords: Adjunct; Anti-cancer peptide; Doxorubicin; Nisin; Skin cancer