Related Experiment Video
Updated: Apr 12, 2026
![Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate DMBA-TPA](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F60445.jpg&w=3840&q=50)
Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate DMBA-TPA
Published on: December 19, 2019
Effect of nisin and doxorubicin on DMBA-induced skin carcinogenesis--a possible adjunct therapy
Simran Preet1, Sanjay Bharati2, Anshul Panjeta2
1Department of Biophysics, Basic Medical Sciences Block-2, Panjab University, Sector-25, Chandigarh, 160014, India. simranpreet@pu.ac.in.
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.
Insights
Nisin combined with doxorubicin (DOX) shows synergistic effects against skin cancer in mice, reducing tumor size and increasing apoptosis. This combination offers a potential strategy to overcome drug resistance in cancer therapy.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Multidrug-resistant cancer cells necessitate novel therapeutic approaches.
- Nisin, an antimicrobial peptide, and doxorubicin (DOX) are investigated for their combined efficacy.
- Skin carcinogenesis models are crucial for evaluating anti-cancer agents.
Purpose of the Study:
- To evaluate the synergistic anti-cancer activity of nisin and doxorubicin (DOX) against DMBA-induced skin carcinogenesis.
- To assess the combination's impact on tumor burden, histological changes, apoptosis, and oxidative/antioxidant status.
Main Methods:
- Animal bioassays were conducted to measure tumor burden and volume.
- Histological analysis of skin tissues was performed.
- In situ apoptosis was quantified using the TUNEL assay.
- Oxidant and antioxidant markers, including lipid peroxidation (LPO) and enzyme activities, were measured.
Main Results:
- The nisin-DOX combination significantly reduced mean tumor burden and volume compared to individual treatments.
- Histological examination revealed chromatin condensation and nuclear marginalization, consistent with increased apoptosis shown by TUNEL assay.
- Adjunct therapy induced mild oxidative stress, with increased LPO and nitrite generation.
- Superoxide dismutase levels marginally increased, while catalase activity decreased in the combination group.
Conclusions:
- Nisin acts synergistically with doxorubicin, demonstrating potent anti-cancer effects in a skin carcinogenesis model.
- The combination therapy promotes apoptosis and may offer a strategy to combat drug-resistant cancers.
- Nisin can be considered a potential adjunct to doxorubicin for overcoming cancer drug resistance.
