ABCG2-ATPase was inhibited by low concentrations of Na-orthovanadate, N-ethylmaleimide and cyclosporin A. Verapamil had no effect, while Fumitremorgin C, reversing ABCG2-dependent cancer drug resistance, strongly inhibited this ATPase activity.
The breast cancer resistance protein (BCRP) gene, formally known as ATP-binding cassette transporter G2 (ABCG2) gene, encodes an ABC half transporter that causes resistance to certain cancer chemotherapeutic drugs when transfected and expressed in drug sensitive cancer cells.
Breast cancer resistance protein (BCRP), an ABC half-transporter, is overexpressed in cancer cell lines selected with doxorubicin/verapamil, topotecan, or mitoxantrone.
We have previously demonstrated a role for the ATP-binding cassette transporter breast cancer resistance protein (BCRP) in MTX resistance (Volk et al., Cancer Res., 62: 5035-5040, 2002).
More prospective studies are needed, preferably combining BCRP protein or mRNA quantification with functional assays, in order to determine the contribution of BCRP to drug resistance in human cancers.
Irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin; CPT-11) is a widely used potent antitumor drug that inhibits mammalian DNA topoisomerase I (Topo I); however, overexpression of ABCG2 (BCRP/MXR/ABCP) can confer cancer cell resistance to SN-38, the active form of CPT-11.
No associations were observed between the BCRPC421A polymorphism and clinicopathologic or epidemiologic factors, including age, gender, tumor grade, stage, cigarette smoking, family history of cancer and body mass index.
The human ABCG2 (BCRP/MXR/ABCP) transporter causes cancer drug resistance by actively extruding a variety of cytotoxic drugs, and it functions physiologically to protect our tissues from xenobiotics.
Among the ABC proteins, some members including ABCB1, ABCC1, ABCC2 and ABCG2 are believed to contribute to multidrug resistance of cancer chemotherapy.
WP744 overcomes transport by Pgp, MRP-1 and BCRP in cell lines and AML cells and is a promising agent for clinical development in AML and other malignancies with broad-spectrum multidrug resistance.
Of particular relevance to cancer chemotherapy are the transporters P-glycoprotein (Pgp) encoded by multidrug resistance 1 gene, multidrug resistance protein (MRP), and breast cancer resistance protein (BCRP).
Many chemo-sensitizing agents have been discovered, which can be developed for increasing drug adsorption and reversing drug resistance in cancer chemotherapy by inhibiting ABCG2 function or expression.
Intriguingly, recently developed molecular targeted cancer drugs, such as the tyrosine kinase inhibitors imatinib mesylate, gefitinib and others, can also interact with BCRP.
Furthermore, we also review evidence suggesting that tyrosine kinase inhibitors, including imatinib and gefitinib, are both direct and downstream inactivators of ABCG2 and, therefore, serve as candidates to reverse cancer stem cell chemoresistance and potentially target cancer stem cells.
Inhibition of ABCG2 and/or MDR1 revealed that resistance of cancer stem cells to doxorubicin may be mainly due to the expression of these ABC transporters that were highly up-regulated in the resistant subline.