Curcumin Co-Treatment Sensitizes Multi-Drug Resistant Ht29 Colon Cancer Cell Line

Abstract

Colorectal cancer has been confirmed to be the third most dreadful cancer across the world. The latest reports show that the colorectal cancer is increasing in India at a high rate due to food habits, particularly consuming the foods with high fat content. Chemotherapy has been considered as a potential treatment in the control of a wide range of cancers recently, such as gastrointestinal cancers and so on. The scientists are looking to come up with new drugs to treat cancer by regulating the carcinogenesis with minimal toxicity. Curcumin is a phytochemical extracted from turmeric. It is highly effective product of the rhizomes of Curcuma longa L. (Zingiberaceae). It is also considered as a valuable drug for chemotherapeutic treatments in cancer. In case of animal studies, it has been clearly mentioned that curcumin controls carcinogenesis in various other organs as well as colon. Curcumin exhibits the capability to act as anti-mutagenic, anti-inflammatory drug as well. It has also been confirmed that the P-gp expression regulation is carried out by curcumin by inhibiting the COX-2 expression. Also, it has been clearly stated that curcumin down-regulates NF-kB pathway in various cell lines like Colo 205 colon cancer cell line etc. Multi Drug Resistance (MDR) plays a key role in case of the cancer cells to exhibit the resistance against the cytotoxicity of various chemotherapeutic drugs. This type of characteristics in cancer cells is developed due to low levels of the chemotherapeutic drug accumulated inside the cells during repeated exposure to the drug, showing the over-expression of P-glycoprotein (MDR-1). P-glycoprotein, a transporter protein, allows the cells to expel the wide range of chemotherapeutic drugs. The latest reports show that COX-2 expression and P-gp expression possess strong correlation with each other. In this research study, we generated the Multi-Drug Resistant HT29 Human colon cancer cells by treating the cells with increasing concentrations of a chemotherapeutic drug namely Doxorubicin Hydrochloride (DOX) and further we estimated the intracellular drug concentration in treated live as well as dead cells with the help of Doxorubicin Accumulation Assay. Also, the cell morphology change was studied in HT29 cells after every 24 hours of the DOX treatment separately as well as curcumin co-treatment (DOX+Curcumin). The curcumin co-treatment was carried out to observe the effect of curcumin on multi-drug resistant HT29 colon cancer cells and further study can be extended to investigate the various inflammatory genes controlled by NFkB at mRNA and protein level as well as the levels of cytokines which may get down-regulated by treatment. This study will help to completely understand the mechanism of reducing the effect of Multidrug Resistance (a unique property of cancer) by curcumin in case of colon cancer.