Application Of Chemometrics Methods In Screening Antitumor Active Components

Cancer is a kind of disease which is seriously harmful to people. More and more research results on screening new drug for cancer therapy were reported. One important the new drug resources was nature products. However, since the nature products were so many, the screening work is burdensome. Randomly screening is laborious and hardly be done. Myxobacteria can produce lots of metabolites which possess anti-cancer cell activities. Epothilones are one of the metabolites which are well known. However, the products of these metabolites are commonly few and unstable. The purification and biological analysis of these metabolites is laborious. Chemometrics is a subject which is focus on application of maths, statistics and compute technology in analytical chemistry. In this paper, chemometrics was used to screen the new anti-cancer metabolites in the broth of myxobacteria.The broth samples of myxobacteria which were fermented under various fermentation conditions and whit fermentation media were collected. The samples were prepared by extracting the metabolites from broth with resin. The anti-cancer cell activities were against nasopharyngeal carcinoma cells CNE, tongue squamous cell carcinoma cell Tca 8113 and homo sapiens carcinoma cell ZR-75-1. The components of samples were analyzed with high performance liquid chromatogram (HPLC). Multi-regression method was employed to model the relationship between the normalized HPLC peaks and the anti-cancer cell actives against nasopharyngeal carcinoma cells CNE, tongue squamous cell carcinoma cell Tca 8113 and homo sapiens carcinoma cell ZR-75-1. T-test method was employed to measure the significances of the coefficients in the multi-linear regression model, in order to screen the new drugs which possess anti-cancer activities against nasopharyngeal carcinoma cells CNE, tongue squamous cell carcinoma cell Tca 8113 and homo sapiens carcinoma cell ZR-75-1. The results were shown as follow:(1) The HPLC peaks of the samples were normalized. The R2 of the model for anti-cancer actives against nasopharyngeal carcinoma cells CNE was 0.5685 which was competent for initially screening metabolites which possess anti-cancer activity. The F-value of the model was 2.7989, and the p-value was 0.0179, which indicated that the model was significant and credible. T-test method was employed to exam the significants of the coefficients in the models and the results demonstrated that five components, namely X5,X9,X42,X49,X52 possess significant anti-cancer activity against nasopharyngeal carcinoma cells CNE. New anti-cancer drug against nasopharyngeal carcinoma cells CNE can be screened according to these results.(2) The HPLC peaks of the samples were normalized. The R2 of the model for anti-cancer activities against nasopharyngeal carcinoma cells CNE was 0.8172 which was competent for initially screening metabolites which possess anti-cancer activity. The F-value of the model was 4.7196, and the p-value was 0.0008, which indicated that the model was significant and credible. T-test method was employed to exam the significants of the coefficients in the models and the results demonstrated that five components, namely X4, X11, X17, X18, X20, X31, X43, X49, X52, X56 possess significances anti-cancer activity against tongue squamous cell carcinoma cell Tca 8113. New anti-cancer drug against tongue squamous cell carcinoma cell Tca 8113 can be screened according to these results.(3) The HPLC peaks of the samples were normalized. The R2 of the model for anti-cancer actives against homo sapiens carcinoma cell ZR-75-1 was 0.8829 which was competent for initially screening metabolites which possess anti-cancer active. The F-value of the model was 33.7258, and the p-value was 1.1132*10-17, which indicated that the model was significant and credible. T-test method was employed to exam the significants of the coefficients in the models and the results demonstrated that seven components, namely X4, X11, X17, X18, X20, X31, X43, X49, X52, X56 possess significant anti-cancer active against homo sapiens carcinoma cell ZR-75-1. New anti-cancer drug against homo sapiens carcinoma cell ZR-75-1 can be screened according to these results.According to the results of HPLC, X49 and X52 were epothilone A and epothilone B respectively. The results demonstrated that epothilone A possess anti-cancer activities against nasopharyngeal carcinoma cells CNE, tongue squamous cell carcinoma cell Tca 8113 and homo sapiens carcinoma cell ZR-75-1, while epothilone A possess anti-cancer activities against nasopharyngeal carcinoma cells CNE, tongue squamous cell carcinoma cell Tca 8113. The similar conclusions can be found in the other literatures. These results also demonstrated the feasibility of this method.