Circadian time-dependent chemopreventive potential of withaferin-A in 7,12-dimethylbenz[a]anthracene-induced oral carcinogenesis.

Content Provider	Semantic Scholar
Author	Manoharan, Shanmugam Panjamurthy, Kuppusamy Balakrishnan, Subramanian Vasudevan, Kalaiarasan Vellaichamy, Lakshmanan
Copyright Year	2009
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.
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://rabbit.if-pan.krakow.pl/pjp/pdf/2009/4_719.pdf
Alternate Webpage(s)	http://www.if-pan.krakow.pl/pjp/pdf/2009/4_719.pdf
Alternate Webpage(s)	http://if-pan.krakow.pl/pjp/pdf/2009/4_719.pdf
Alternate Webpage(s)	http://rabbit.if-pan.krakow.pl/pjp/pdf/2009/4_719_ab.pdf
Alternate Webpage(s)	http://www.if-pan.krakow.pl/pjp/pdf/2009/4_719_ab.pdf
PubMed reference number	19815955v1
Volume Number	61
Issue Number	4
Journal	Pharmacological reports : PR
Language	English
Access Restriction	Open
Subject Keyword	9,10-Dimethyl-1,2-benzanthracene Abnormal cell Administration, Oral Adverse reaction to drug Antioxidants Buccal surface CATALASE Carcinogenesis Cell Proliferation Chronotherapy GLUTATHIONE PEROXIDASE Hamsters Lipid Peroxidation Mesocricetus auratus Neoplasms Pouch - device Squamous Epithelial Cells Squamous cell carcinoma Superoxide Dismutase Superoxides Thiobarbituric Acid Reactive Substances therapeutic index withaferin A
Content Type	Text
Resource Type	Article