Phorbol ester and okadaic acid-resistant cells: the crossroads of signal transduction and drug resistance.
Many factors are involved in the development of drug resistance for anticancer drugs. The drugs should pharmacokinetically attain the appropriate concentration. They should be metabolized to the active forms. Tumor cells should have sensitivity to them. Several molecular and biochemical mechanisms that may explain cellular drug resistance have been identified. The contribution of protein phosphorylation and dephosphorylation for drug resistance is demonstrated in phorbol ester and okadaic-acid-resistant cells. The modulation of drug resistance by substances that affect the signal transduction pathway is an important issue in the development of an effective method for overcoming drug resistance.
Saijo
N
N
Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan.
Nishio
K
K
Takeda
Y
Y
Arioka
H
H
Ishida
T
T
Nomoto
T
T
Fukuoka
K
K
Kurokawa
H
H
Fukumoto
H
H
D000970:Antineoplastic Agents / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D018432:Drug Resistance, Multiple; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D019319:Okadaic Acid; D010703:Phorbol Esters / Q000494:pharmacology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D000970:Antineoplastic Agents; D002273:Carcinogens; D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D009363:Neoplasm Proteins; D010703:Phorbol Esters; D019319:Okadaic Acid; D004317:Doxorubicin; D011505:Protein-Tyrosine Kinases; D002945:Cisplatin