Title : Integrative approach to combat cancer
Abstract:
Use of herbal medicines alone and in combination with conventional anticancer agents has increased remarkably in cancer patients. However, lack of scientific evidence has limited the use of these cocktails. Thus it is necessary to evaluate the effect of these combinations alone and with anticancer drugs. This study investigates the chemotherapeutic potential of extracts of H. mystax (HM), N. nimmoniana (NN), Ocimum tenuiflorum (OT) and their combinations with Camptothecin and Cisplatin against KB cell line. The 95% ethanol (E) and aqueous plant extracts (by soxhletion) were quantified for the presence of phenolic acids by RP – HPLC method. In vitro cytotoxicity analysis of individual extracts and in combination was performed by MTT assay. Selective toxicity of plant extracts were checked using normal cell line. The isobologram and combination index (CI) method of Chou-Talalay were used to evaluate the interactions between extract(s) and drug. Dose reduction index (DRI) was calculated. Synergistic combinations induced cancer cell death was analyzed by Annexin V – PI assay. Ethanol and aqueous extracts have shown presence of caffeic acid, catechol, vanillin, gallic acid and p–coumaric acid. The ethanol extract of selected plants showed potent activity against KB cells. These extracts were also studied in combination with anticancer agents. Fifteen combinations were prepared using constant drug ratio of their median effect dose. Four combinations viz., HM-E:NN-E, NN-E:OT-E, HM-E:NN-E:OT-E and HM-E:NN-E:Cisplatin showed synergistic growth inhibitory effect. Combination Index values (CI) at different dose levels (IC50 – IC90) ranging from 1.01 to 0.13 for HM-E: NN-E, 1.00 - 0.16 for NN-E: OT-E, 1.11 - 0.26 for HM-E:NN-E:OT-E and 0.65 to 1.15 for HM-E: NN-E: Cisplatin respectively after 24 hr exposure on cervical cancer cell line. The dose reduction level was different for each combination. Synergistic combination exposure induced characteristic changes and showed significant cell death in KB cells. Herbal mixtures alone or in combination with anticancer agent(s) produced a synergistic effect in inhibiting cervical cancer cells. Therefore, herbals in combination alone and with anticancer drugs may help to increase therapeutic index and minimize dose related toxicity of anticancer treatments. However, further in vivo studies are needed to check its therapeutic efficacy and safety
