Regulation of mutual inhibitory activities between AMPK and Akt with quercetin in MCF-7 breast cancer cells.
In lieu of elucidating bidirectional connecting mechanism between AMP-activated protein kinase (AMPK) and survival signal Akt we applied MCF-7 breast cancer cells to determine whether AMPK modulation alters Akt signals and vice versa. Suppression of Akt activities with a synthetic Akt inhibitor alleviated AMPK activities suggesting that Akt is capable of inhibiting AMPK. Also the activation of AMPK with quercetin strongly abrogated Akt activities. Treating cancer cells with AMPK siRNA or Compound C resulted in marked increment of Akt dephosphorylation indicating that AMPK has antagonistic activities towards Akt. However, quercetin exerted Akt inhibitory activities in the absence of AMPK activation. Quercetin induced partial co-localization of phospho-Akt and phospho-AMPK in the nucleus even though their interaction seems to be indirect since the immunoprecipitation data indicate there was no direct binding between total Akt and AMPK. These results suggest there is a mutual suppressive interaction between AMPK and Akt. The investigation of mutual suppression between Akt and AMPK by chemo-preventive agents such as quercetin may provide a mechanistic rational for controlling breast tumor cell growth.
Department of Food and Nutrition, Hannam University Daedeok Valley Campus, Yuseong-gu, Daejeon 305-811, Republic of Korea.
Yun-Kyoung
YK
Lee
Ock Jin
OJ
Park
D000263:Adenylate Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000502:physiology; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D008954:Models, Biological; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011794:Quercetin / Q000494:pharmacology* / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000494:pharmacology
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D011794:Quercetin; D051058:Oncogene Protein v-akt; D000263:Adenylate Kinase