Table 1.
The molecular details of the contribution of apoptosis, necrosis, cell cycle arrest as well as autophagy to cancer preventive activities of flavonoids
| Flavonoids | Mechanism of action (Cytotoxicity profiling) | Ref. |
|---|---|---|
| Casticin | Activation of caspase-9, -8, -3; p38 MAPK activation associated with histone H3 phosphorylation (Apoptosis induction, G2/M arrest) | [24] |
| Cytochrome C release, activation of caspase-9, -3 and PARP, activation of JNK; Decrease of mitochondria membrane potential associated with dysregulation of Bax/Bcl-2 pathway (Apoptosis induction, G2/M arrest) | [36] | |
| Activation of caspase-9, -3 and PARP, upregulation of Bax and p27; Inhibition of Bcl-2, cyclin D1/CDK4, Akt (Apoptosis induction; G0/G1 arrest) | [37] | |
| Upregulation of p53, Bax, caspase-3 and p21; Inhibition of polymerization of tubulin, cyclin B1 and CDK1 (Apoptosis induction, G2/M arrest) | [38] | |
| Induction of death receptor 5 and Bax, activation of caspase-3 and PARP; Downregulation of Bcl-xL, Bcl-2, survivin, cFLIP, XIAP, pro-form Bid (Apoptosis induction) | [39] | |
| Activation of FOXO3a along with downregulation of FOXM1, CDK1, cdc25B, cyclin B1 and upregulation of p27 (G2/M arrest) | [47] | |
| Vitexin | Activation of intrinsic apoptotic pathway associated with decrease of Bcl-2/Bax ratio, mitochondria membrane potential, cytochrome c release and activation of caspase-3; Inhibition of PI3K/Akt/mTOR (Apoptosis induction) | [40] |
| Quercetin | Activation of intrinsic apoptotic pathway associated with upregulation of Bax, Bad, Bid, caspase-9, -3, downregulation of Bcl-2; Bcl-xL, and cytochrome c release (Apoptosis induction) | [41] |
| Activation of caspase-3; Inhibition of thymidylate synthase (Necrosis and apoptosis induction, S phase arrest) | [50] | |
| Kaempferol | Upregulation of p53 and cleaved-PARP; Inhibition of ERα, Bcl-2, survivin (Apoptosis induction; G2/M arrest) | [43] |
| Upregulation of phosphorylated AMPK, Atg-5, Atg-7, Atg-12, Beclin 1 and LC3-II; Downregulation of CDK1/cyclin B, phosphorylation of Akt and mTOR (G2/M arrest, autophagy induction) | [53] | |
| Flavone; apigenin; luteolin | Activation of FOXO3a along with upregulation of p27, p21, and downregulation of cyclin B; cyclin D1, induction of p53, cleaved-PARP, cytochrome C; Inhibition of PI3K/Akt pathway (G1, S, and/or G2/M arrest) | [45] |
| Wogonin | Upregulation of GATA-1 and p21; Downregulation of CDK4, cyclin D1, MEK and ERK (G0/G1 arrest) | [46] |
| Delphinidin; Cyanidin-3-rutinoside | Induction of cellular vacuolization and LC3-II (Apoptosis, autophagy and necrosis) | [49] |
Abbreviations: AMPK, adenosine monophosphate activated protein kinase; CDK4, cyclin-dependent kinase 4; cFLIP, cellular FLICE-like inhibitory protein; ERα, estrogen receptor alpha; ERK, extracellular signal regulated kinase; FOXM1, forkhead box M1; FOXO3a, forkhead box O3a; GATA-1, GATA-binding factor 1; JNK, Jun-N-terminal kinase; MAPK, mitogen-activated protein kinase; MEK, mitogen-activated protein kinase kinase; mTOR, mammalian target of rapamycin; PARP, poly ADP-ribose polymerase; PI3K, phosphoinositide 3-kinase; XIAP, X-linked inhibitor of apoptosis protein.