ABSTRACT
In systemic therapy, chemotherapeutic drugs, often, cause considerable side effects; and combination of natural compounds lessen the extent of such effects. In the present study, combined effect of citral and 5-fluorouracil was studied in Schizosaccharomyces pombe cells. The antagonistic combination index found was at 0.01 and 0.025 mM of citral with 40 µg or higher concentration of 5-fluorouracil. The combined treatment was so effective that higher number of cells underwent apoptosis compared to individual treatment of 5-fluorouracil. Citral controlled ROS levels and increased survival of normal cells. Several differentially expressed proteins observed in the citral treatment could further help understanding its mechanism of action.
Subject(s)
Apoptosis/drug effects , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Fluorouracil/antagonists & inhibitors , Fluorouracil/toxicity , Fungal Proteins/analysis , Monoterpenes/pharmacology , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Schizosaccharomyces/drug effects , Schizosaccharomyces/growth & development , Schizosaccharomyces/metabolismABSTRACT
CMF is a combination of anticancer chemotherapeutic agents Cyclophosphamide, Methotrexate and 5-Fluorouracil. Vitamin E protects the basolateral membrane (BSM) from CMF induced lipid peroxidative damages. Rats were treated intravenously with cyclophosphamide-10 mg, methotrexate-1.0 mg and 5-fluorouracil-10 mg per kg body weight for six cycles. Vitamin E (600 mg/kg body weight) was administered orally, daily. Intestinal basolateral membrane bound ATPases (3.6.1.3), Alkalinephosphatase (3.1.1) and 5'-Nucleotidase (3.1.3.5) were protected by co-administration of vitamin E with CMF. In CMF treated rats the lipid peroxidation levels were found to be elevated with a significant depletion in membrane sulfhydryl groups. In vitamin E co-administered animals, the enzyme activities were found to be restored with concomitant reduction in malondialdehyde levels and an increase in the sulfhydryl groups. The membrane cholesterol and phospholipid levels which were altered in CMF treated rats were bought back to the normal in co-administration of vitamin E.