AMP-activated protein kinase (AMPK) is a heterotrimeric serine/threonine kinase that consists of a catalytic α subunit and regulatory β
and γ subunits, each of which has at least two isoforms. The activation of AMPK occurs by binding MK2206 of AMP to the γ subunit, and phosphorylation of Thr172 in the activation loop of the α catalytic subunit by upstream kinases, such as LKB1 and calmodulin-dependent protein kinase kinase (CaMKK) . AMPK is activated under ATP-depleting stresses such as glucose deprivation, hypoxia, and ischemia, and plays a pivotal role in energy homeostasis. Recent studies indicate that AMPK plays a role in linking metabolic syndrome and cancer  and . The AMPK signaling network contains a number of tumor suppressor genes, including LKB1, p53, and TSC2. The tumor suppressor LKB1 has been identified as an upstream activator of AMPK, and other tumor suppressors—p53 and TCS2—are direct substrates of AMPK . In addition PARP inhibitor to causing cell death, AMPK activation can protect cancer cells against apoptosis in several cases. For example, AMPK activation diminishes apoptosis exposed to anticancer
drugs in human gastric carcinoma  and glucose deprivation in pancreas cancer cells . Thus, AMPK has pleiotropic functions in regulating cell proliferation and apoptosis, and it is possible that AMPK might be a future target for therapy or prevention of the metabolic syndrome and some cancers. In this study, we examined the effect of six ginsenosides on cell growth inhibition
of the human hepatoma cell line HepG2. Among them, ginsenoside-Rh2 showed the most potent ability to inhibit the growth of cancer cells. Here, we show that some cancer cells have varying sensitivities to ginsenoside-Rh2-induced apoptosis, raising questions concerning the mechanism of inconsistent responses to ginsenoside-Rh2. We discovered that the degree of ginsenoside-Rh2-induced AMPK activation correlates Edoxaban with differences in sensitivity to apoptosis in cancer cell lines. We also observed that p38 MAPK (mitogen-activated protein kinase) acts as a survival factor under ginsenoside-Rh2 treatment, but there was no crosstalk between AMPK and p38 MAPK. HepG2, HeLa, DU145, and HCT116 cells were maintained in RPMI supplemented with 10% heat-inactivated fetal bovine serum (FBS) and antibiotics at 37°C with 95% air and 5% CO2. RPMI Medium 1640 and FBS were purchased from Life Technologies (Grand Island, NY, USA). Compound C was a generous gift from Merck (Darmstadt, Germany). SP600125 and SB203580 were obtained from TOCRIS (Ellisville, MO, USA).