Multidrug resistance (MDR) can be attributed to the overexpression of an ATP-binding cassette transporter (ABC transporter, P-glycoproteins) and/ or similar ABC proteins. ABC transporters are highly conserved across all known phyla, and are involved in the trans-membrane export of a large number of metabolic products in addition to lipophilic anti-neoplastic drugs. These MDR- associated transporters with associated ATPase are associated with a variety of therapeutic failures with lipophilic, antitumor drugs. This study encompasses the effects of tetrandrine (TET) (6,6’,7,12-tetramethoxy-2,2’-dimethyl-1 beta-berbaman) on two different ovarian cancer cell lines drug resistant human cancer cell lines. Resistance to paclitaxel (PCT) or doxorubicin (DOX) ie., adriamycin was displayed. Drug resistance was measured using the MTT redox assay with the drug resistant (NCI-ADR-RES) and drug susceptible (OVCAR8) ovarian cancer cell lines. Using a partially purified MDR-ATPase assay using ATP-luciferase luminescence, the effects of tetrandrine on the ABC/ATPase transporter was measured. The combination of a primary anti-cancer drug [either paclitaxel (PCT) or doxorubicin (DOX)] with tetrandrine display 100-200 fold reduction respectively in the IC50 (inhibitory concentration at 50% response for (PCT) and (DOX).Tetrandrine appears to be effective against ABC transporters partly due to a decrease in ATP availability to the MDR-1 pump. This could limit energy for the primary drug being pumped outside the cell. Hydrophobic TET is a competitive substrate for the pumping action of other hydrophobic drugs like (PCT) or (DOX) or other known substrates of the pump.
INHIBITORY EFFECT OF TETRANDRINE AND PACLITAXEL OR DOXORUBICIN ON MULTI-DRUG-RESISTANT (MDR) CANCER CELLS ASSOCIATED WITH MDR-ATPASE