2. Academic Validation
  3. Preventive effect of D-carvone during DMBA induced mouse skin tumorigenesis by modulating xenobiotic metabolism and induction of apoptotic events

Preventive effect of D-carvone during DMBA induced mouse skin tumorigenesis by modulating xenobiotic metabolism and induction of apoptotic events

  • Biomed Pharmacother. 2019 Mar:111:178-187. doi: 10.1016/j.biopha.2018.12.071.
Thamizharasi Gopalakrishnan 1,  Sindhu Ganapathy 2,  Veeravarmal Veeran 3,  Nalini Namasivayam 1
Affiliations

Affiliations

  • 1 Department of Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar, 608 002, Tamil Nadu, India.
  • 2 Department of Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar, 608 002, Tamil Nadu, India. Electronic address: ganapathysindhu@gmail.com.
  • 3 Department of Oral & Maxillofacial Pathology, Rajah Muthiah Dental College & Hospital, Annamalai Nagar, 608 002, Tamil Nadu, India.
PMID: 30583225 DOI: 10.1016/j.biopha.2018.12.071
Abstract

The structural integrity and excellent immune system of the skin makes it a protective covering, inspite of its exposure to hazardous compounds. In the present study, the chemopreventive efficacy of D-carvone was studied in 7, 12-dimethylbenz[a]anthracene (DMBA) induced skin carcinogenesis. DMBA (25 μg in 0.1 m L-1acetone) was used to induce skin Cancer in Swiss albino mice. Animals were randomly divided into six groups of six Animals in each. Different concentrations of D-carvone (10, 20, 30 mg/kg body weight) were used to assess its Anticancer effect. Tumor incidence, tumor volume, tumor burden, histological examination and levels of phase I and phase II detoxification agents were analyzed in experimental Animals. Further, expression of p53 and various apoptotic proteins including- Bcl-2, Bax was analyzed using immunohistochemistry and enzymatic expression of apoptotic proteins Caspase-3 and caspase-9 was carried out by using ELISA. We observed 100% tumor incidence in DMBA-painted Animals and our results showed that D-carvone at 20 mg dose significantly prevents skin carcinogenesis. Our results also showed decreased levels of phase I Enzymes (Cyt P450 and-Cyt b5) with increased levels of phase II Enzymes (GR, GST and GSH) and increased expression of Bax, Caspase-3 and caspase-9 with decreased expression of mutated p53 and Bcl-2 in Animals treated with DMBA and D-carvone at 20 mg dose. The results of the present study suggest that D-carvone can be used as a chemopreventive agent against skin Cancer, as it induces Apoptosis in Cancer. However, further studies are warranted to check chemopreventive efficacy of D-carvone on cell proliferation, angiogenesis, and metastasis before going to human trial.

Keywords

Apoptosis; D-carvone; DMBA; Detoxification; Skin carcinogenesis.

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