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Bba, a synthetic derivative of 23-hydroxybutulinic acid, reverses multidrug resistance by inhibiting the efflux activity of MRP7 (ABCC10).


ABSTRACT: Natural products are frequently used for adjuvant chemotherapy in cancer treatment. 23-O-(1,4'-bipiperidine-1-carbonyl) betulinic acid (BBA) is a synthetic derivative of 23-hydroxybutulinic acid (23-HBA), which is a natural pentacyclic triterpene and the major active constituent of the root of Pulsatillachinensis. We previously reported that BBA could reverse P-glycoprotein (P-gp/ABCB1)-mediated multidrug resistance (MDR). In the present study, we investigated whether BBA has the potential to reverse multidrug resistance protein 7 (MRP7/ABCC10)-mediated MDR. We found that BBA concentration-dependently enhanced the sensitivity of MRP7-transfected HEK293 cells to paclitaxel, docetaxel and vinblastine. Accumulation and efflux experiments demonstrated that BBA increased the intracellular accumulation of [(3)H]-paclitaxel by inhibiting the efflux of [(3)H]-paclitaxel from HEK293/MRP7 cells. In addition, immunoblotting and immunofluorescence analyses indicated no significant alteration of MRP7 protein expression and localization in plasma membranes after treatment with BBA. These results demonstrate that BBA reverses MRP7-mediated MDR through blocking the drug efflux function of MRP7 without affecting the intracellular ATP levels. Our findings suggest that BBA has the potential to be used in combination with conventional chemotherapeutic agents to augment the response to chemotherapy.

SUBMITTER: Chen JJ 

PROVIDER: S-EPMC3775757 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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bba, a synthetic derivative of 23-hydroxybutulinic acid, reverses multidrug resistance by inhibiting the efflux activity of MRP7 (ABCC10).

Chen Jun-Jiang JJ   Patel Atish A   Sodani Kamlesh K   Xiao Zhi-Jie ZJ   Tiwari Amit K AK   Tiwari Amit K AK   Zhang Dong-Mei DM   Li Ying-Jie YJ   Yang Dong-Hua DH   Ye Wen-Cai WC   Chen Si-Dong SD   Chen Zhe-Sheng ZS  

PloS one 20130917 9


Natural products are frequently used for adjuvant chemotherapy in cancer treatment. 23-O-(1,4'-bipiperidine-1-carbonyl) betulinic acid (BBA) is a synthetic derivative of 23-hydroxybutulinic acid (23-HBA), which is a natural pentacyclic triterpene and the major active constituent of the root of Pulsatillachinensis. We previously reported that BBA could reverse P-glycoprotein (P-gp/ABCB1)-mediated multidrug resistance (MDR). In the present study, we investigated whether BBA has the potential to re  ...[more]

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