Multidrug-resistant Carcinoma Cell Line Research Articles

ABC Proteins Protect the Human Body and Maintain Optimal Health

Human MDR1, a multi-drug transporter gene, was isolated as the first of the eukaryote ATP Binding Cassette (ABC) proteins from a multidrug-resistant carcinoma cell line in 1986. To date, over 25 years, many ABC proteins have been found to play important physiological roles by transporting hydrophobic compounds. Defects in their functions cause various diseases, indicating that endogenous hydrophobic compounds, as well as water-soluble compounds, are properly transported by transmembrane proteins. MDR1 transports a large number of structurally unrelated drugs and is involved in their pharmacokinetics, and thus is a key factor in drug interaction. ABCA1, an ABC protein, eliminates excess cholesterol in peripheral cells by generating HDL. Because ABCA1 is a key molecule in cholesterol homeostasis, its function and expression are highly regulated. Eukaryote ABC proteins function on the body surface facing the outside and in organ pathways to adapt to the extracellular environment and protect the body to maintain optimal health.

The riminophenazine agents clofazimine and B669 inhibit the proliferation of intrinsically multidrug resistant carcinoma cell lines.

The sensitivity to clofazimine, B669 and eight standard anti-tumour chemotherapeutic agents of four intrinsically multidrug resistant (MDR) cell lines [three human hepatocellular carcinoma cell lines (HepG2, PLC and Mahlavu) and a human colorectal carcinoma cell line (CaCo2)] were compared with that of a human cervix epithelioid carcinoma cell line (HeLa). The MDR cell lines and HeLa cells showed equivalent sensitivity to the riminophenazines, methotrexate and 5-fluorouracil, but exhibited ranging levels of resistance to vinblastine, doxorubicin, mitomycin C, daunorubicin, etoposide and vincristine. Riminophenazines may be useful agents in the chemotherapy of tumours with intrinsic MDR.