Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.11 (AMPK)
 12,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer is still a global public health problem, which is the leading cause of death in most countries. Ginseng has been used for centuries all over the world as a panacea that promotes longevity. As the king of herb plants, ginseng holds great promise as a new treatment option which is used either by itself or in combination with other medicinal ingredients that is widely accepted as complementary and alternative medicine in cancer therapy. Ginsenosides, the major pharmacologically active ingredients of ginseng, have been shown to have multiple medicinal effects including prominent anticancer activity. The purpose of this review is to give our perspective about the roles of ginsenosides in reactive oxygen species (ROS)-mediated anticancer therapy. Additionally, to provide new sheds light for further improvement and carry out pre-clinical and clinical trials to develop it successfully into a potential anticancer agent. Panax herbs and their derivate/metabolites ginsenosides exert beneficial effects for treating various types of cancers. The mechanism of ROS-mediated anticancer activities of ginsenosides varies depending on the specific type of cancer cells involved. Ginsenosides may suppress cancer cell proliferation through anti-oxidation on tumor initiation and induce apoptosis, paraptosis or autophagy via generation of ROS on tumor progression, promotion, angiogenesis, invasion and metastasis by various signaling pathways e.g., activation of AMPK, MEK, ASK-1/JNK, ESR2-NCF1-ROS, ER-dependent PI3K/Akt/Nrf2, P53-CHOP, ROS-JNK-autophagy, and/or inhibition of PI3K/Akt signaling pathways. These multiple effects rather than a single may play a crucial role in emerging ginsenosides as a successful anticancer drug.
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PMID:Role of ginsenosides in reactive oxygen species-mediated anticancer therapy. 2941 26

PI3K/Akt signaling is activated in cancers and governs tumor initiation and progression, but how Akt is activated under diverse stresses is poorly understood. Here we identify AMPK as an essential regulator for Akt activation by various stresses. Surprisingly, AMPK is also activated by growth factor EGF through Ca2+/Calmodulin-dependent kinase and is essential for EGF-mediated Akt activation and biological functions. AMPK phosphorylates Skp2 at S256 and promotes the integrity and E3 ligase activity of Skp2 SCF complex leading to K63-linked ubiquitination and activation of Akt and subsequent oncogenic processes. Importantly, AMPK-mediated Skp2 S256 phosphorylation promotes breast cancer progression in mouse tumor models, correlates with Akt and AMPK activation in breast cancer patients, and predicts poor survival outcomes. Finally, targeting AMPK-mediated Skp2 S256 phosphorylation sensitizes cells to anti-EGF receptor targeted therapy. Our study sheds light on how stress and EGF induce Akt activation and new mechanisms for AMPK-mediated oncogenesis and drug resistance.
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PMID:The critical role of AMPK in driving Akt activation under stress, tumorigenesis and drug resistance. 3041 6