The relationship between energy status and AMP-activated protein kinase in human H460 lung cancer cells.
In cultured cells, glucose and serum provide constant sources of energy and growth factors, both of which are important for cell survival and proliferation. AMP-activated protein kinase (AMPK) plays a key role in sensing intracellular ATP levels and acts as a critical regulator of energy homeostasis. To investigate the relationship between energy status and AMPK activity in lung cancer, H460 cells were starved in either glucose-free or serum-free medium and then re-stimulated with glucose and serum, respectively. The levels of ATP and lactate and the activities of AMPK and lactate dehydrogenase (LDH) were analyzed at different time intervals. During glucose treatment, the activity of AMPK was induced by glucose and showed biphasic reaction kinetics. The ATP level was gradually increased up to 2-fold compared with that in serum treatment after 24 h and lactate level was decreased to approximately 60%. The LDH activity slightly increased and reached a peak after 6 h. During serum treatment, the activity of AMPK was suppressed and the ATP level showed a dramatic 30% increase after 1 h. In contrast, the lactate level was gradually increased and then reverted to the background level after 24 h. The activity of LDH was slightly decreased after 12 h and eventually returned to the background level. This study showed the alteration of energy status in lung cancer cells in response to altered levels of glucose and serum. We suggest that the activation of AMPK and inhibition of glycolysis might be exploited as therapeutic tactics in cancer treatment.
Su
Mei-Yin
MY
Department of Physical Education, National Taiwan Normal University, Taipei City, ROC.
Hsieh
Shen-Yu
SY
Lee
Yi-Ru
YR
Chang
Ming-Chuan
MC
Yuan
Thomas Ta-Tung
TT
Chang
Jia-Ming
JM
D055372:AMP-Activated Protein Kinases; D000255:Adenosine Triphosphate / Q000378:metabolism; D045744:Cell Line, Tumor; D016895:Culture Media, Serum-Free; D015536:Down-Regulation; D004734:Energy Metabolism / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D045022:Lactate Dehydrogenases / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism*; D015854:Up-Regulation
D016895:Culture Media, Serum-Free; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D045022:Lactate Dehydrogenases; D055372:AMP-Activated Protein Kinases; D005947:Glucose