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Chemopreventive effect of 4'-demethyl epipodophyllotoxin on DMBA/TPA-induced mouse skin carcinogenesis
D Dhawan1, S Balasubramanian, A J Amonkar
1Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029 and Cancer Research Institute, Parel Mumbai, India.
Abstract:
The chemopreventive effect of topical application of 4'-demethyl epipodophyllotoxin (DMEP), an antimitotic agent, on a two-stage skin carcinogenesis model in Swiss Albino mice induced by 9, 10-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) was investigated. Two topical applications with 0.24% DMBA over 1 week, followed later by 5 nmol of TPA twice weekly produced 100% incidence of tumors in these animals by 18 weeks. Treatment of animals with DMEP (until the end of the experiment), 30 min before TPA treatment, significantly reduced the tumor incidence, tumor volume and the conversion efficiency of papillomas to squamous cell carcinomas. The tumor formation and growth was also delayed by DMEP pre-treatment. Application of DMEP protected against the losses provoked in levels of glutathione and activity of catalase and superoxide dismutase in skin and liver of animals by the application of DMBA/TPA. Thus, DMEP might possibly be exerting its chemopreventive activity by acting as an antioxidant.
Insights
4'-demethyl epipodophyllotoxin (DMEP) demonstrated chemopreventive effects against skin cancer in mice. DMEP reduced tumor development and protected against oxidative stress, suggesting antioxidant properties may underlie its efficacy.
Area of Science:
- Oncology
- Dermatology
- Pharmacology
Background:
- Skin carcinogenesis is a complex process often studied using chemical induction models.
- 9, 10-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) are commonly used carcinogens in experimental skin cancer research.
- Antimitotic agents are being explored for their potential chemopreventive properties.
Purpose of the Study:
- To investigate the chemopreventive potential of 4 omino-demethyl epipodophyllotoxin (DMEP) in a chemically induced mouse skin carcinogenesis model.
- To evaluate the effect of DMEP on tumor incidence, volume, and progression to squamous cell carcinoma.
- To assess the impact of DMEP on key antioxidant markers in the skin and liver.
Main Methods:
- A two-stage skin carcinogenesis model was established in Swiss Albino mice using DMBA and TPA.
- DMEP was topically applied 30 minutes prior to TPA treatment throughout the experiment.
- Tumor incidence, volume, progression, and levels of glutathione and antioxidant enzyme activities (catalase, superoxide dismutase) were measured.
Main Results:
- DMEP treatment significantly reduced tumor incidence, tumor volume, and the conversion of papillomas to squamous cell carcinomas.
- Pre-treatment with DMEP delayed the onset and growth of tumors.
- DMEP application protected against DMBA/TPA-induced depletion of glutathione and inhibited the decrease in catalase and superoxide dismutase activity.
Conclusions:
- Topical application of DMEP exhibits significant chemopreventive effects against DMBA/TPA-induced skin carcinogenesis in mice.
- DMEP's ability to mitigate oxidative stress, evidenced by preserved glutathione levels and antioxidant enzyme activity, suggests it acts as an antioxidant.
- These findings highlight DMEP as a potential candidate for skin cancer chemoprevention strategies.
![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)