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Circadian time-dependent chemopreventive potential of withaferin-A in 7,12-dimethylbenz[a]anthracene-induced oral carcinogenesis.
Pharmacol Rep. 2009 Jul-Aug; 61(4):719-26.PR

Abstract

Circadian time-dependent treatment with chemotherapeutic drugs (chronotherapy) optimizes the therapeutic index by maximizing treatment efficacy and minimizing toxicity. The circadian time-dependent chemopreventive and anti-lipid peroxidative efficacy of withaferin-A in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis was investigated in the present study. We induced oral squamous cell carcinoma in the buccal pouches of golden Syrian hamsters during the day (4:00, 8:00, 12:00, 16:00, 20:00 and 24:00) by application of DMBA three times per week for 14 weeks. The circadian time-dependent tumor incidence, volume and burden were observed in hamsters treated with either DMBA alone or DMBA + withaferin-A. The circadian pattern of lipid peroxidation by-products, as measured by the formation of thiobarbituric acid reactive substances (TBARS) and enzymatic antioxidants [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)], was also analyzed in the buccal mucosa of DMBA-treated hamsters. We found the highest incidence of tumor formation at 24.00 h in hamsters treated with DMBA alone as compared to other experimental groups. Circadian dysregulation of lipid peroxidation and antioxidant status was observed in DMBA-treated animals as compared to control animals. Oral (po) administration of withaferin-A (20 mg/kg) completely prevented the formation of tumors between 8.00 h and 12.00 h and synchronized the status of lipid peroxidation and antioxidants in the buccal mucosa of hamsters treated with DMBA alone. Also, oral administration of withaferin-A to DMBA-treated animals significantly reduced the formation of tumors and synchronized the status of lipid peroxidation and antioxidants in the rest of the time intervals. Our study thus suggests that withaferin-A has significant chemopreventive and anti-lipid peroxidative potential in DMBA-induced oral carcinogenesis, probably by interfering with DMBA-induced abnormal cell proliferation in the buccal mucosa.

Authors+Show Affiliations

Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India. rasmanshisak@gmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19815955

Citation

Manoharan, Shanmugam, et al. "Circadian Time-dependent Chemopreventive Potential of withaferin-A in 7,12-dimethylbenz[a]anthracene-induced Oral Carcinogenesis." Pharmacological Reports : PR, vol. 61, no. 4, 2009, pp. 719-26.
Manoharan S, Panjamurthy K, Balakrishnan S, et al. Circadian time-dependent chemopreventive potential of withaferin-A in 7,12-dimethylbenz[a]anthracene-induced oral carcinogenesis. Pharmacol Rep. 2009;61(4):719-26.
Manoharan, S., Panjamurthy, K., Balakrishnan, S., Vasudevan, K., & Vellaichamy, L. (2009). Circadian time-dependent chemopreventive potential of withaferin-A in 7,12-dimethylbenz[a]anthracene-induced oral carcinogenesis. Pharmacological Reports : PR, 61(4), 719-26.
Manoharan S, et al. Circadian Time-dependent Chemopreventive Potential of withaferin-A in 7,12-dimethylbenz[a]anthracene-induced Oral Carcinogenesis. Pharmacol Rep. 2009 Jul-Aug;61(4):719-26. PubMed PMID: 19815955.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Circadian time-dependent chemopreventive potential of withaferin-A in 7,12-dimethylbenz[a]anthracene-induced oral carcinogenesis. AU - Manoharan,Shanmugam, AU - Panjamurthy,Kuppusamy, AU - Balakrishnan,Subramanian, AU - Vasudevan,Kalaiarasan, AU - Vellaichamy,Lakshmanan, PY - 2008/09/30/received PY - 2009/06/06/revised PY - 2009/10/10/entrez PY - 2009/10/10/pubmed PY - 2010/7/23/medline SP - 719 EP - 26 JF - Pharmacological reports : PR JO - Pharmacol Rep VL - 61 IS - 4 N2 - Circadian time-dependent treatment with chemotherapeutic drugs (chronotherapy) optimizes the therapeutic index by maximizing treatment efficacy and minimizing toxicity. The circadian time-dependent chemopreventive and anti-lipid peroxidative efficacy of withaferin-A in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis was investigated in the present study. We induced oral squamous cell carcinoma in the buccal pouches of golden Syrian hamsters during the day (4:00, 8:00, 12:00, 16:00, 20:00 and 24:00) by application of DMBA three times per week for 14 weeks. The circadian time-dependent tumor incidence, volume and burden were observed in hamsters treated with either DMBA alone or DMBA + withaferin-A. The circadian pattern of lipid peroxidation by-products, as measured by the formation of thiobarbituric acid reactive substances (TBARS) and enzymatic antioxidants [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)], was also analyzed in the buccal mucosa of DMBA-treated hamsters. We found the highest incidence of tumor formation at 24.00 h in hamsters treated with DMBA alone as compared to other experimental groups. Circadian dysregulation of lipid peroxidation and antioxidant status was observed in DMBA-treated animals as compared to control animals. Oral (po) administration of withaferin-A (20 mg/kg) completely prevented the formation of tumors between 8.00 h and 12.00 h and synchronized the status of lipid peroxidation and antioxidants in the buccal mucosa of hamsters treated with DMBA alone. Also, oral administration of withaferin-A to DMBA-treated animals significantly reduced the formation of tumors and synchronized the status of lipid peroxidation and antioxidants in the rest of the time intervals. Our study thus suggests that withaferin-A has significant chemopreventive and anti-lipid peroxidative potential in DMBA-induced oral carcinogenesis, probably by interfering with DMBA-induced abnormal cell proliferation in the buccal mucosa. SN - 1734-1140 UR - https://www.unboundmedicine.com/medline/citation/19815955/Circadian_time_dependent_chemopreventive_potential_of_withaferin_A_in_712_dimethylbenz[a]anthracene_induced_oral_carcinogenesis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1734-1140(09)70125-2 DB - PRIME DP - Unbound Medicine ER -