Chemotherapeutic efficacy of paclitaxel in combination with Withania somnifera on benzo(a)pyrene-induced experimental lung cancer.
Lung cancer is one of the leading causes of cancer death in the world and is notoriously difficult to treat effectively. In the present study, male Swiss albino mice were divided into five groups of six animals each: group I animals received corn oil orally and served as a control; group II cancer-induced animals received benzo(a)pyrene (50 mg/kg bodyweight dissolved in corn oil, orally) twice weekly for four successive weeks; group III cancer-bearing animals (after 12 weeks of induction) were treated with paclitaxel (33 mg/kg bodyweight, i.p.) once weekly for 4 weeks; group IV cancer-bearing animals were treated with paclitaxel along with Withania somnifera (400 mg/kg bodyweight) orally once weekly for 4 weeks; and group V animals constituted the drug control treated with paclitaxel along with W. somnifera. The serum, lung and liver were investigated biochemically for aryl hydrocarbon hydroxylase, gamma-glutamyl transpeptidase, 5'-nucleotidase, lactate dehydrogenase and protein-bound carbohydrate components (hexose, hexosamine and sialic acid). These enzyme activities were increased significantly in cancer-bearing animals compared with control animals. The elevation of these in cancer-bearing animals was indicative of the persistent deteriorating effect of benzo(a)pyrene in cancer-bearing animals. Our data suggest that paclitaxel, administered with W. somnifera, may extend its chemotherapeutic effect through modulating protein-bound carbohydrate levels and marker enzymes, as they are indicators of cancer. The combination of paclitaxel with W. somnifera could effectively treat the benzo(a)pyrene-induced lung cancer in mice by offering protection from reactive oxygen species damage and also by suppressing cell proliferation.
Senthilnathan
Palaniyandi
P
Department of Medical Biochemistry, ALM Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600-113, India.
Padmavathi
Radhakrishnan
R
Magesh
Venkatraman
V
Sakthisekaran
Dhanapal
D
D015720:5'-Nucleotidase / Q000032:analysis; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000032:analysis; D001564:Benzo(a)pyrene; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood; D001835:Body Weight; D006023:Glycoproteins / Q000032:analysis; D006595:Hexosamines / Q000032:analysis / Q000737:chemistry; D006601:Hexoses / Q000032:analysis / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000097:blood; D008168:Lung / Q000201:enzymology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000032:analysis / Q000097:blood; D017239:Paclitaxel / Q000627:therapeutic use*; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D028321:Plant Preparations / Q000627:therapeutic use; D018517:Plant Roots / Q000737:chemistry; D011073:Polyamines / Q000032:analysis; D047368:Tumor Burden; D032341:Withania / Q000737:chemistry*; D005723:gamma-Glutamyltransferase / Q000032:analysis
D014408:Biomarkers, Tumor; D006023:Glycoproteins; D006595:Hexosamines; D006601:Hexoses; D010936:Plant Extracts; D028321:Plant Preparations; D011073:Polyamines; D001564:Benzo(a)pyrene; D007770:L-Lactate Dehydrogenase; D001189:Aryl Hydrocarbon Hydroxylases; D005723:gamma-Glutamyltransferase; D015720:5'-Nucleotidase; D019158:N-Acetylneuraminic Acid; D017239:Paclitaxel