title: Chemomodulatory Potential of Bartogenic Acid Against DMBA/Croton Oil Induced Two-Step Skin Carcinogenesis in Mice.
abstract: Barringtonia racemosafruits are believed to be useful in cancer treatment in Ayurveda, the Indian system of medicine. In present study, bartogenic acid (BA), a triterpenoid constituent of Barringtonia fruits was evaluated for its cytotoxicity property using the human skin carcinoma cell line (SCC-13) and human peripheral blood mononuclear cells (PBMC). The chemopreventive efficacy of BA was evaluated against the DMBA/Croton oil-induced skin carcinogenesis in mice.BA was orally administered at the doses of 1, 2 or 4 mg/kg/day or applied topically every day for 12 weeks following DMBA application. Thein vitrodata from cell lines revealed that BA induces cytotoxicity against the SCC-13 cells (IC50=7.5 µM). It was found 4.05 times more selective to exert cytotoxicity against SCC-13 as compared to the PBMC (IC50=30.4 µM). Thein vivodatacollected from mice model of DMBA/Croton oil-induced skin carcinogenesis revealed that BA administered orally or applied topically, both reduced the precancerous skin lesions andthe incidence of tumor bearing. The oral doses of BA (2 and 4 mg/kg) and topical treatment significantly reduced the incidence and number of skin papillomas. At these doses, BA also increased the activities of catalase and superoxide dismutase and induced an increase in glutathionecontent and inhibited lipid peroxidation in the skin. These findings reveal the chemopreventive efficacy of BA and also demonstrate that it contributes to the cytotoxic and antioxidative effects ofBarringtonia racemosafruits. The study also validates the traditional claims of Barringtonia fruits and provides a scientific basis of its chemopreventive property.
authors.affiliation: Department of Pharmacology R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Maharashtra, India.
authors.forename: Chandragouda R
authors.initials: CR
authors.lastname: Patil
authors.affiliation: Department of Pharmacology R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Maharashtra, India.
authors.forename: Bhavin M
authors.initials: BM
authors.lastname: Sonara
authors.affiliation: Department of Pharmacology R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Maharashtra, India.
authors.forename: Umesh B
authors.initials: UB
authors.lastname: Mahajan
authors.affiliation: Department of Pharmacology, H. R. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Maharashtra, India.
authors.forename: Kalpesh R
authors.initials: KR
authors.lastname: Patil
authors.affiliation: Department of Pharmaceutical Chemistry, H. R. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Maharashtra, India.
authors.forename: Dipak D
authors.initials: DD
authors.lastname: Patil
authors.affiliation: Department of Pharmacognosy, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Maharashtra, India.
authors.forename: Ramchandra B
authors.initials: RB
authors.lastname: Jadhav
authors.affiliation: Department of Pharmacology R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Maharashtra, India.
authors.forename: Sameer N
authors.initials: SN
authors.lastname: Goyal
authors.affiliation: Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, PO Box- 17666, Al Ain, Abu Dhabi, UAE.
authors.forename: Shreesh
authors.initials: S
authors.lastname: Ojha
keywords: Bartogenic acid; Chemoprevention; DMBA/Croton oil; Natural products; Phytochemicals.; Skin Cancer; Two-stage skin carcinogenesis