Table 1.
Chemopreventive/chemotherapeutic phytochemicals that activate AMPK.
| Phytochemical | Effect | Reference |
| CURCUMIN | ||
| Curcumin (diferuloylmethane), from turmeric (Curcuma longa L.) | Activates AMPK to induce cell death in CaOV3 ovarian cancer cells in a p38 MAPK-dependent manner | (67) |
| Stimulates AMPK, resulting in downregulation of PPARγ in 3T3-L1 adipocytes and in COX-2 in MCF-7 breast cancer cells, inhibiting differentiation and growth | (65) | |
| Inhibits mTOR, independent of AMPK | (64) | |
| Downregulates COX-2 and pAKT in an AMPK-dependent manner, leading to apoptosis of H29 colon cancer cells | (66) | |
| GRAPE POLYPHENOLS | ||
| Resveratrol | Induces apoptosis in chemoresistant HT-29 colon cancer cells via modulation of AMPK signaling pathway | (74) |
| Activates AMPK and suppresses LPS-induced NF-κB-dependent COX-2 activation in RAW 264.7 macrophage cells | (75) | |
| Promotes autophagy-mediated cell death in chronic myelogenous leukemia cells in an AMPK-dependent manner | (76) | |
| 3,4-DMS, a methylated resveratrol derivative, induced autophagy in endothelial cells through activation of AMPK and the downstream inhibition of mTOR signaling pathway | (80) | |
| Activates AMPK via SIRT1 in both ER-positive and ER-negative breast cancer cells, leading to inhibition of 4E-BP1 signaling and mRNA translation via mTOR | (105) | |
| Enhances prostate cancer cell response to ionizing radiation by modulation of AMPK | (78) | |
| Inhibits AKT/mTOR signaling via AMPK and potentiates the effects of gefitinib in breast cancer | (77) | |
| Enhances anti-tumor effects of temozolomide in glioblastoma via ROS-dependent AMPK-TSC-mTOR signaling pathway | (79) | |
| FLAVONOIDS | ||
| Apigenin | Induces AMPK and autophagy, inhibiting mTOR, and further inducing autophagy in both HaCaT cell line and primary normal human epidermal keratinocytes. This effect was independent of AKT and LKB1 but dependent on CaMMKβ | (90) |
| Anthocyanin | Activates AMPK, leading to a reduction in mTOR phosphorylation and inhibition of HT-29 colon cancer cell growth | (106) |
| Fisetin | Activates AMPK to induce apoptosis in multiple myeloma cells | (85) |
| Inhibits PI3K/Akt and mTOR and activates AMPK in non-small cell lung cancer | (86) | |
| Induces autophagy-mediated cell death by suppressing mTOR in prostate cancer cells | (87) | |
| Quercetin | Induces apoptosis via AMPK activation and p53 in HT-29 colon cancer cells | (88) |
| Suppresses cell viability via AMPK-induced Hsp70 and EGFR downregulation | (89) | |
| Baicalein | Induces apoptosis and AMPK in human tumor cells | (107) |
| Luteolin | Induces cell death in HepG2 cells and reduces tumor volume in a tumor xenograft model | (91) |
| Hispidulin | Activates AMPK and inhibits downstream mTOR, which induces apoptosis in glioblastoma multiforme cells by p53 and p21 induction | (108) |
| Genistein | Decreases reactive oxygen species levels and induces antioxidant enzymes manganese superoxide dismutase and catalase in a AMPK and PTEN-dependent manner in prostate cancer cells | (82) |
| Potentiates arsenic trioxide-induced apoptosis in human leukemia cells by activation of AMPK | (83) | |
| Deguelin | Activates AMPK and inhibits UVB-induced tumorigenesis in the SKh-1 hairless mouse model | (92) |
| Tephrosin (plant rotenoid) | Enhances cytotoxicity of anti-cancer agent via ATP depletion and reducing autophagy by activation of AMPK and inactivation of mTOR expression | (109) |
| Chrysin | Leads to cell growth inhibition and apoptosis in lung cancer cells via activation of AMPK and inhibition of AKT/mTOR | (94) |
| Celastrol | Suppresses breast cancer MCF-7 cell viability via the AMP-activated protein kinase (AMPK)-induced p53-polo like kinase 2 (PLK-2) pathway | (93) |
| GREEN TEA POLYPHENOLS | ||
| Epigallocatechin gallate (EGCG) | EGCG analogs activate AMPK, leading in inhibition of cell proliferation, up-regulation of the cyclin-dependent kinase inhibitor p21, downregulation of the mTOR pathway, and suppression of stem cell population in human breast cancer cells | (96) |
| Enhances 5-fluorouracil-induced cell growth inhibition of hepatocellular carcinoma cells, associated with AMPK hyperactivation and COX-2 inhibition | (98) | |
| Activates AMPK in the liver and prevents diethylnitrosamine-induced liver tumorigenesis in obese and diabetic mice | (97) | |
| Induces apoptosis in HT-29 colon cancer cells via the AMPK/COX-2 pathway | (95) | |
| Catechin | Induces apoptosis in colon cancer cells by attenuation of H2O2-stimulated COX-2 expression via AMPK | (110) |
| OTHER CATEGORY | ||
| p-HPEA-EDA, phenolic compound of virgin olive oil | Activates AMPK to suppress COX-2 and inhibit cell survival in HT-29 colon cancer cells | (102) |
| 24-Hydroxyursolic acid from persimmon | Activates AMPK and induces apoptosis in HT-29 colon cancer cells; Also block EGF-induced ERKs phosphorylation and inhibits AP-1 activity and cell transformation | (101) |
| Capsaicin | Induces apoptosis in HT-29 colon cancer cells, which correlated with AMPK activation in capsaicin-treated colon cancer cells | (103) |
| Berberine | Inhibits colon cancer migration via AMPK activation-mediated downregulation of integrin b1 signaling | (100) |
| Berberine-induced AMPK activation inhibits the metastatic potential of tumor cells through a reduction in the activity of the ERK signaling pathway and COX-2 protein levels | (99) | |