Chemomodulatory Potential of Bartogenic Acid Against DMBA/Croton Oil Induced Two-Step Skin Carcinogenesis in Mice

Abstract

Barringtonia racemosa fruits 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. The in vitro data 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). The in vivo datacollected 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 of Barringtonia racemosa fruits. The study also validates the traditional claims of Barringtonia fruits and provides a scientific basis of its chemopreventive property.

C‐type natriuretic peptide (CNP) inhibits 7,12‐Dimethylbenz[a]anthracene (DMBA)/Croton oil‐induced skin tumor growth by modulating inflammation in Swiss albino mice

“…DMBA, a polycyclic aromatic hydrocarbon has been used to induce irreversible mutation in the cells, [26,27] followed by the repeated application of a tumor-promoter or 12-O-tetradecanoyng agent-phorbol ester phorbol-13-acetate (TPA) is the active constituent from croton oil and it induces accumulation of pro-inflammatory cytokine/chemokines in the skin, which in turn tumor promotion/progression levels. [28][29][30] Hence, in the present investigation, the anticancer activity of CNP was studied individually, and also in combination with CDDP in the DMBA/Croton oil-induced two-step skin carcinogenesis mouse model.…”

“…DMBA, a polycyclic aromatic hydrocarbon has been used to induce irreversible mutation in the cells, [ 26,27 ] followed by the repeated application of a tumor‐promoter or 12‐O‐tetradecanoyng agent‐phorbol ester phorbol‐13‐acetate (TPA) is the active constituent from croton oil and it induces accumulation of pro‐inflammatory cytokine/chemokines in the skin, which in turn tumor promotion/progression levels. [ 28–30 ]…”

Chemomodulatory Potential of n-Hexane Extract of Conyza bonariensis Against Skin Carcinogenesis in Mice Induced by Carcinogens: An in Vitro and in Vivo Study

“…Extract The SCC13 cells were procured from ATCC (Manassas, VA), and human PBMC was isolated by density centrifugation of heparinized blood of healthy donors using the dextran T-500 sedimentation method (Patil et al 2016). The cells were grown adherently in RPMI-1640 media supplemented with 10% fetal calf serum, 100 U/mL penicillin, and 100 µg/mL streptomycin at 37°C in 5% CO2 with 95% air (Saleem et al 2015).…”

Protective effect of Barringtonia racemosa Ethyl Acetate Fraction against Cisplatin-induced Nephrotoxicity in Rats

“…[14,15] B. racemosa contains several biologically active phytoconstituents, amongst which bartogenic acid, a natural pentacyclic triterpenoid, is well known for its biological properties, including α-glucosidase inhibitor, anti-arthritic, and anti-cancer. [16][17][18] It has also been reported that various parts of B. racemosa exhibit many pharmacological effects, like anti-oxidant, [14,15,19] anti-inflammatory, [20] anti-fungal, [21] anti-cancer, [22] analgesic, [23] anti-tuberculosis, [24] and anti-diarrhoea activity. [25] To our knowledge, there are no reports on the protective role of B. racemosa or bartogenic acid against anti-cancer drug-induced nephrotoxicity.…”