Science-based holistic philosophy of Chinese Medicine Formula: reflected in cytotoxicity of Tian-xian Liquid (in vitro) and the protein expression of p21, MMP-1 andMDR-1 in human colorectal carcinoma (in vivo) in response to Tian-xian Liquid

Abstract

AIM: This study aims at investigating the holistic effects of three functional constituent fractions obtained from Tian-xian Liquid (TXL) contributing to anti-tumorigenicity of TXL in human colorectal carcinoma in vivo and in vitro. METHODOLOGY: TXL and its functional constituent fractions, including fractions of ethyl-acetate (EA), butanol (BU) and aqueous (WA), were prepared. Tissue-specific proliferative effects of TXL and its three functional constituent fractions on human colorectal carcinoma HT-29 cells and splenocytes were studied by using MTT assay. Protein levels of p21, MMP-1 and MDR-1 in a xenografted nude mice model were examined by Western blot analysis. RESULTS AND DISCUSSION: TXL exerted anti-tumorigenicity in human colorectal carcinoma with tissue-specific cytotoxicity, through the interactions among its different functional fractions. The anti-proliferative action of BU and EA fractions were tissue-specific, in which BU fraction was anti-proliferative to HT-29 cells but proliferative to mouse splenocytes, whereas EA fraction was anti-proliferative to splenocyte but with far less effect on HT-29 cells. Besides, the response of p21, MMP-1 and MDR-1 revealed that all functional fractions worked together to exhibit mutual accentuation (相須) and/or mutual enhancement (相使) effects to achieve anti-proliferation, anti-metastasis and reversion of multi-drug resistance in anti-tumorigenicity. BU fraction and EA fraction exerted mutual counteraction (相殺) and mutual suppression (相畏) in anti-proliferative effects on splenocytes, and WA fraction and EA fraction demonstrated mutual antagonism (相惡) in anti-proliferative effects on HT-29 cells. CONCLUSION: This is the first study to elucidate the science behind the holistic philosophy of Chinese Medicine formula for treating colon cancer, through investigating into anti-tumorigenicity of TXL and its functional constituent fractions. Further research in this area may give hints to the development of more tissue-specific effective drugs with minimal side effects for fighting against human colorectal carcinoma.