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Can the therapeutic effects of temozolomide be potentiated by stimulating AMP‐activated protein kinase with olanzepine and metformin?
Author(s) -
Kast RE,
KarpelMassler G,
Halatsch ME
Publication year - 2011
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2011.01320.x
Subject(s) - metformin , ampk , temozolomide , medicine , amp activated protein kinase , pharmacology , protein kinase a , olanzapine , apoptosis , cancer research , oncology , diabetes mellitus , kinase , chemotherapy , endocrinology , schizophrenia (object oriented programming) , chemistry , biochemistry , psychiatry
As current treatments for glioblastoma commonly fail to cure, the need for more effective therapeutic options is overwhelming. Here, we summarize experimental evidence in support of the suggestion that metformin and olanzepine have potential to enhance the cytotoxic effects of temozolomide, an alkylating chemotherapeutic agent commonly used to treat glioblastoma. Although the primary path leading to temozolomide‐induced cell death is formation of O‐6‐methylguanine and apoptotic signalling triggered by O‐6‐methyl G:T mispairs, that apoptotic signalling goes through a step mediated by AMP‐activated protein kinase (AMPK). Metformin or olanzapine have been shown independently to enhance AMPK activation. Metformin to treat diabetes and olanzapine to treat psychiatric disorders are well tolerated and have been used clinically for many years. Thus it should be feasible to increase AMPK activation and add to the pro‐apoptotic effects of temozolomide, by adding metformin and olanzapine to the therapeutic regimen. Clinical assessment of the potential benefit of such combined therapy against glioblastoma is warranted.