[HTML][HTML] NQO1-induced activation of AMPK contributes to cancer cell death by oxygen-glucose deprivation

H Lee, ET Oh, BH Choi, MT Park, JK Lee, JS Lee… - Scientific reports, 2015 - nature.com
H Lee, ET Oh, BH Choi, MT Park, JK Lee, JS Lee, HJ Park
Scientific reports, 2015nature.com
Oxygen and glucose deprivation (OGD) due to insufficient blood circulation can decrease
cancer cell survival and proliferation in solid tumors. OGD increases the intracellular
[AMP]/[ATP] ratio, thereby activating the AMPK. In this study, we have investigated the
involvement of NQO1 in OGD-mediated AMPK activation and cancer cell death. We found
that OGD activates AMPK in an NQO1-dependent manner, suppressing the mTOR/S6K/4E-
BP1 pathway, which is known to control cell survival. Thus, the depletion of NQO1 prevents …
Abstract
Oxygen and glucose deprivation (OGD) due to insufficient blood circulation can decrease cancer cell survival and proliferation in solid tumors. OGD increases the intracellular [AMP]/[ATP] ratio, thereby activating the AMPK. In this study, we have investigated the involvement of NQO1 in OGD-mediated AMPK activation and cancer cell death. We found that OGD activates AMPK in an NQO1-dependent manner, suppressing the mTOR/S6K/4E-BP1 pathway, which is known to control cell survival. Thus, the depletion of NQO1 prevents AMPK-induced cancer cell death in OGD. When we blocked OGD-induced Ca2+/CaMKII signaling, the NQO1-induced activation of AMPK was attenuated. In addition, when we blocked the RyR signaling, the accumulation of intracellular Ca2+ and subsequent activation of CaMKII/AMPK signaling was decreased in NQO1-expressing cells under OGD. Finally, siRNA-mediated knockdown of CD38 abrogated the OGD-induced activation of Ca2+/CaMKII/AMPK signaling. Taken together, we conclude that NQO1 plays a key role in the AMPK-induced cancer cell death in OGD through the CD38/cADPR/RyR/Ca2+/CaMKII signaling pathway.
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