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Multidrug resistance (MDR) is a multifactorial phenomenon considered to be the main cause of failure in cancer chemotherapy. One of the underlying mechanisms of MDR is the overexpression of membrane transporter proteins, such as P-glycoprotein (P-gp/ABCB1) and multidrug resistance-associated protein 1 (MRP1/ABCC1). As these proteins are also expressed in normal tissues, considerable attention has been dedicated to the search for cytotoxic drugs that are not substrates for these proteins. This study investigated the effects of betulinic acid (BA) on the activity of ABCB1 and ABCC1 in Ma-104, a non-tumoral renal cell line constitutively expressing both proteins. The results indicated that concentrations of BA with low cytotoxicity to Ma-104 did not alter the activity of ABCB1 or ABCC1, nor did BA interfere with the accumulation of a classic chemotherapeutic, methotrexate. This suggests it would also be a good choice for use in drug cocktails. The lack of effect of BA on ABCB1 and ABCC1, as well as its antitumoral properties, suggest that this triterpene is a viable chemotherapeutic agent for MDR tumors.

molecular medicine reports

Betulinic acid does not modulate the activity of P-gp/ABCB1 or MRP1/ABCC1 in a non-tumoral renal cell line: Possible utility in multidrug resistance cancer chemotherapy