Copper transporters regulate the cellular pharmacology and sensitivity to Pt drugs

Combined modalities of resistance in an oxaliplatin-resistant human gastric cancer cell line with enhanced sensitivity to 5-fluorouracil

“…Although evidence of cross-resistance between CDDP and oxaliplatin exists (Rixe et al, 1996;Safaei and Howell, 2005), oxaliplatin has been frequently shown to be effective against tumours with primary or acquired resistance to CDDP (Cvitkovic, 1998;Misset et al, 2000). Conversely, CDDP is rarely tested in oxaliplatin-resistant cancer cells either in vivo or in vitro.…”

“…In contrast to extensive studies of the cellular pharmacology of CDDP, little is known about how cells become resistant to oxaliplatin. Recent work has identified pivotal roles of copper transporters in trafficking platinum compounds through cells and controlling their activities in cells (Safaei and Howell, 2005). However, most of our knowledge comes either from CDDP-resistant cell lines or from cell lines manipulated by transfection with these transporters.…”

“…This action led to reduced platinum cytotoxicity . Available information consistently provided strong evidence that ATP7B mediates resistance to platinum drugs by regulating drug efflux, and tumours with higher ATP7B expression did show an unfavourable response to platinum drug treatment (Safaei and Howell, 2005). However, most of these reports explored the association between ATP7B overexpression and CDDP or carboplatin resistance.…”

Carboplatin and taxol resistance develops more rapidly in functional BRCA1 compared to dysfunctional BRCA1 ovarian cancer cells

“…This indicates the possible involvement of copper transporters ATP7A, ATP7B and CTR1 in carboplatin resistance (Safaei et al 2005). However western blots for ATP7A and CTR1…”

Administration of isothiocyanate (E-4IB) and cisplatin leads to altered signalling and lysosomal export in human ovarian carcinoma sensitive- and cisplatin-resistant cells

“…Re peated exposure of cancer cells to CDDP results in the devel opment of resistance to metaloids, including CDDP, and this resistance is associated with alterations in DNA re pair, drug accu mu lation [2,3] and linked with the ex pression of several transporters, particularly the copper protein Ctr1, metallochaperons and P-type ATP-ase trans porters ATP7A and ATP7B [4,5]. In various cells CDDP can activate mul tiple sig naling pathways, in cluding those involving p53, Bcl-2 family, caspases, cyclins, CDKs, pRb, PKC, PI3K/Akt and MAPKs (JNK, p38 and ERK), and other signal trans duction pathways [6].…”