Antroquinonol displays anticancer potential against human hepatocellular carcinoma cells: A crucial role of AMPK and mTOR pathways

Small-molecule COH-SR4 inhibits adipocyte differentiation via AMPK activation

“…Consequently, knockdown of AMPKα1/α2 prevented dephosphorylation of both mTORC1 effectors, with noticeable absence of cell cycle arrest and inhibition of protein expression of key transcription factors and their target lipogenic genes. These findings are consistent with several studies where AMPK activators were shown to block S6K and 4E-BP phosphorylation (48,49), and the failure of AMPK agonist AICAR to inhibit mTORC activity in AMPKα1/α2 double knockout mice embryonic fibroblasts (50). Nonetheless, to better understand whether inhibition of adipocyte differentiation by COH-SR4 is directly mediated through AMPK-mTORC1 signaling and cell cycle arrest, future investigations assessing the effects of the compound on raptor and/or TCS2-deficient, as well as p27-knockdown 3T3 cells are warranted.…”

Exogenous cell-permeable C6 ceramide sensitizes multiple cancer cell lines to Doxorubicin-induced apoptosis by promoting AMPK activation and mTORC1 inhibition

“…The apoptosis rate was quantified in Figure 2b. The synergistic effects of C6 ceramide and Doxorubicin on cancer cell apoptosis were also confirmed by using Histone DNA apoptosis enzyme-linked immunosorbent assay ( Figure 2c Doxorubicin induces AMPK activation in multiple cancer cell lines in vitro As discussed above, activation of AMPK pathway serves as an important cellular mechanism in regulating cell apoptosis (Morgillo et al, 2006;Kim do et al, 2009;Chiang et al, 2010). We next, test the possible role of this signal pathway in Doxorubicin-induced cancer cell death/apoptosis.…”

“…Recent findings suggest that AMPK inhibits cell growth and proliferation, and also positively regulates apoptosis (Ravid et al, 1999;Morgillo et al, 2006;Nithipongvanitch et al, 2007;Okoshi et al, 2007;Cao et al, 2008;Kim do et al, 2009;Chiang et al, 2010). These findings are not surprising, given that cell growth, DNA replication and mitosis are all major consumers of ATP, and also that the upstream regulator of AMPK, LKB1, is known to be a tumor suppressor.…”

“…AMPK activation also triggers a phosphorylation cascade that regulates the activity of various downstream targets, including transcription factors, enzymes and other regulatory proteins, such as mTOR pathways (Inoki et al, 2003), p53 (Jones et al, 2005) and p38 (Yoon et al, 2006). The key function of AMPK is to regulate the energy balance within the cell; however, recent studies also indicate that AMPK activation modulates other important cellular functions, including promoting apoptosis (Morgillo et al, 2006;Cao et al, 2008;Kim do et al, 2009;Chiang et al, 2010). …”

Induction of apoptosis by ethanol extract of <i>Evodia rutaecarpa</i> in HeLa human cervical cancer cells <i>via</i> activation of AMP-activated protein kinase

“…Although AMPK might give cancer cells a survival advantage by conservation of energy in ATP-depleted conditions (14), it has been generally considered as a tumor suppressor based on the following points: i) AMPK deactivates mTOR, which is commonly activated in many cancers; ii) most of the tumor suppressor genes, including LKB1 and phosphatase and tensin homolog (PTEN), have been identified as upstream activators of AMPK (43,44); and iii) AMPK activators, such as 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and metformin, are reported to inhibit tumorigenesis and tumor growth (45,46). Notably, metformin and antroquinonol have been reported to activate AMPK to induce apoptosis by inducing mitochondrial stress (47,48). Avicin D also disrupts mitochondrial metabolism, leading to decreased ATP levels and activation of AMPK, which is followed by autophagic cell death (41).…”