AMP-activated protein kinase (AMPK) is a critical energy-balancing sensor in the regulation of cellular metabolism in response to external stimuli. Emerging evidence has suggested that AMPK is a potential therapeutic target for human
cancers.
AICAR, one of the pharmacological AMPK activators, has been widely used to suppress
cancer cell growth through activation of LKB1, an upstream
kinase of AMPK. However, frequent mutations and deletions of LKB1 found in some
cancer cells limit the application of
AICAR as an efficient therapeutic
drug. Here we show that an alternative pharmacological AMPK activator,
A23187, was able to inhibit
cervical cancer cell growth through activation of
Ca(2+)/calmodulin-dependent protein kinase kinase beta, another upstream
kinase of AMPK. Using
cervical cancer cell models, we found that HeLa (LKB1-deficient cell) responded less to the anti-proliferative effect exerted by
AICAR treatment (p < 0.001) compared with CaSki and C41 (LKB1-expressing cells). Conversely, the anti-proliferative effect was increased significantly in HeLa but not in CaSki and C41 cells under treatment by
A23187 (p < 0.001). Moreover, co-treatment of
AICAR and
A23187 was able to further enhance the inhibitory effect on cell growth of Hela, CaSki and C41 cells. Notably, both
AICAR and
A23187 exerted the anti-proliferative effect on
cervical cancer cells by suppressing AMPK/mTOR signalling activity. These data suggest that
A23187 could be an alternative potential therapeutic
drug used for anti-proliferation in LKB1-deficient
cancer cells.