Schematic diagram of apoptosis. After factors such as FasL, APO-3L, APO-2L, and TNF-α attaching to the receptors located in cell membrane, apoptosis begins. Bad and Mcl-1 protein regulate Bcl-2 family, which control release of proteins from the space between the mitochondrial inner and outer membrane. Then, Bcl-2 family regulates proteins such as Cyto C, and Cyto C activates caspase-9. Finally, Caspase-9 induces apoptosis [68,69]. On the other hand, apoptosis also occurs by caspase-3, which is activated by caspase-8 and caspase-10. Various natural products induced apoptosis by regulating key molecules of apoptosis. Abbreviation: AIF, Apoptosis-inducing factor; Akt, Protein kinase B, Ask1, Apoptosis signal-regulating kinase 1; APO-3L/TWEAK, APO3 ligand or TNF-related weak inducer of apoptosis; APO-2L/TRAIL, Apo2 ligand or tumor necrosis factor-related apoptosis-inducing ligand; Bad, BCL2 associated agonist of cell death; Bax, Bcl-2 Associated X-protein; Bcl-2, B-cell lymphoma 2; BID, BH3 Interacting Domain Death Agonist; Casp-8, Caspase-8; Casp-10, Caspase-10; Casp-9, Caspase-9; Casp-3, Caspase-3; CD95, cluster of differentiation 95; clAP1/2, cellular inhibitor of apoptosis 1 and 2; CYLD, Cylindromatosis; Cyto C, Cytochrome c; DR3, Death Receptor 3; DR4/5 Death receptor 4, 5; EECU, Ethanol extracts of peel; Erk, Extracellular signal-regulated kinase; FasL, Fas ligand; KSY, Kuan-Sin-Yin; GCBE, green coffee bean extract; LBP, Lycium barbarum polysaccharides; Mcl-1, Myeloid cell leukemia 1; MKK1, Mitogen-activated protein kinase kinase 1; MWE, Mulberry Water Extract; NF-kB, Nuclear factor kappa B; p90RSK, p90 ribosomal S6 kinase; p53; PTEN, phosphatase and tensin homolog; PFE, Pomegranate fruit ethanol extract; PI3K, Phosphoinositide 3-kinase; Puma, p53 up-regulated modulator of apoptosis; RIP, Receptor-interacting protein; TNF- α, tumor necrosis factor-α; TNF-R1, Tumor necrosis factor receptor 1; TRADO; GSE, Grape seed extract; XIAP, X-linked inhibitor of apoptosis protein; YME, yerba mate extract; YMEX, yerba mate extract. Reprinted/adapted with permission from Ref. [70]. 2013, ApexBio Technology.