Telomerase inhibition combined with other chemotherapeutic reagents to enhance anti-cancer effect.
Genetic experiments using a dominant-negative form of human telomerase (DN-hTERT) demonstrated that telomerase inhibition can result in telomeric shortening followed by proliferation arrest and cell death by apoptosis. Neoplastic cells from telomerase RNA null (mTERC-/-) mice showed enhanced chemosensitivity to doxorubicin or related double-strand DNA break (DSB)-inducing agents. Telomerase dysfunction, rather than telomerase inhibition, is proposed to be the principal determinant governing chemosensitivity specifically to DSB-inducing agents. We observed that imatinib and vincristine (VCR), in addition to DSB-inducing agents, also enhanced chemosensitivity in telomestatin-treated K562 cells. This observation suggests that combined use of telomerase inhibitors and imatinib or other chemotherapeutic agents may be a very useful approach to treatment of BCR-ABL-positive leukemia.
Tauchi
Tetsuzo
T
First Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan.
Ohyashiki
Junko H
JH
Ohyashiki
Kazuma
K
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D004357:Drug Synergism; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D010080:Oxazoles / Q000494:pharmacology / Q000627:therapeutic use; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D019098:Telomerase / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D001549:Benzamides; D010080:Oxazoles; D010879:Piperazines; D011743:Pyrimidines; C431888:telomestatin; D000068877:Imatinib Mesylate; D019098:Telomerase