Caspase-mediated apoptosis

Singh AV, Xiao D, Lew KL, Dhir R, Singh SV. (2004) Sulforaphane induces caspase-mediated apoptosis in cultured PC-3 human prostate cancer cells and retards growth of PC-3 xenografts in vivo. Carcinogenesis 25 83-90. 

Wang, Z. He, Q.Y. Liang, Y.Y. Wang, D.S. Li, Y.Y. Li, D.D. Non-caspase-mediated apoptosis contributes to the potent cytotoxicity of the enediyne antibiotic lidamycin toward human tumor cells. Biochem. Pharmacol. 2003, 65, 1767-1775. 

To confirm the noninvolvement of the caspase pathway, cytotoxicity and apoptosis induction were studied in the presence of a caspase-3 inhibitor (Z-DEVD-FMK) and a negative control for the caspase-3 inhibitor (Z-FA-FMK). The negative control only inhibited cysteine protease and had no inhibitory effect on caspase-mediated apoptosis. The presence of a caspase-3 inhibitor, as well as a negative control, did not alleviate the cytotoxicity of 13-MTD and did not prevent induction of apoptosis. 

Apple-derived procyanidin Esophageal adenocarcinoma Induced caspase-mediated apoptosis and an arrest of the cell cycle in G0/G1 [150]... 

BNS-22 is a chemically synthesized derivative of the natural plant product GUT-70. GUT-70 has been reported to inhibit leukemic cell growth and induce caspase-mediated apoptosis [17]. Among more than 60 derivatives of GUT-70, BNS-22 was selected as the compound with the most robust biological activity. However, its molecular target and mechanism of action remained unknown. 

Oommen, S., Anto, R.J., Srinivas, G. et al. (2004) Allicin (from garlic) induces caspase-mediated apoptosis in cancer cells. Eur. J. Pharmacol, 485, 97-103. 

Xiao H, Rawal M, Hahm ER, Singh SV Benzo[a]pyrene-7,8-diol-9,10-epoxide causes caspase-mediated apoptosis in H460 human lung cancer cell line. Cell Cycle 2007, 6 2826-2834. 

Pervaiz S, Hirpara JL, Clement M-V (1998) Caspase proteases mediate apoptosis induced by anticancer preactivated MC540 in human tumor lines. Cancer Lett 128 11-22... 

High doses of trichothecenes promote rapid onset of leukocyte apoptosis which likely contributes to immunosuppression. DON and other trichothecenes cause apoptosis in vitro in primary T-cells, B-cells and IgA+ B cells20 as well as HL-60,53 U937 and RAW 264.7 cell lines43 via caspase-mediated mechanisms.54 These in vitro findings are relevant to the intact animal since in vivo administration of trichothecenes to rodents results in apoptosis in thymus, spleen and bone marrow.55-56 Capacity of a trichothecene to induce apoptosis corresponds to ability to inhibit translation.57... 

It is now well estahlished that activation of the caspase cascade is an indispensable and sufficient process in the execution phase of apoptosis (Nunez et al, 1998). As for mitochondria-mediated apoptosis, cytochrome c released from the mitochondrial inner membrane is well known to play an important role in the activation of caspase 9, one of the upstream proteases in the cascade (Zou et al, 1997). For activation of caspase 9, cytochrome c or apoptotic protease activating factor 2 (Apaf 2) induces the formation of the complex between Apaf 1 and caspase 9. The resultant activated caspase 9 then activates caspase 3, which in turn leads to the genomic DNA fragmentation and apoptotic cell death. 

This ceramide-mediated apoptosis was shown to be inhibited by the simultaneous addition of PKC activators (Ni et at, 1994 Obeid et al, 1993), implying that PS may activate the ceramide-mediated apoptotic pathway. However, the inhibitors of interleukin-1 converting enzyme (ICE)-like proteases (Caspase), such as tosyl-L-lysine chloromethyl ketone (TLCK), and tosyl-L-phenylalanine chloromethyl ketone (TPCK) which inhibit ceramide-mediated apoptosis, had no effect on PS-induced apoptosis (Figure 4). Thus, PS-induced apoptotic pathway appears to be distinct from that mediated by ceramide. Further studies are required to clarify the molecular mechanisms underlying the PS-induced apoptosis. 

Cuvilher, O., Rosenthal, D. S., Smulson, M. E., and Spiegel, S., 1998, Sphingosine 1-phosphate inhibits activation of caspases that cleave poly(ADP-iibose) polymerase and lamins during Eas- and ceramide-mediated apoptosis in Jurkat T lymphocytes. J. Biol. Chem. 273 2910-2916. 

Caspase-mediated cleavage of specific substrates can explain several of the characteristic features of apoptosis. For example, cleavage of the nuclear lamins and cytoplasmic proteins such as fodrin and gelsolin are required for nuclear and cellular... 

CTL-mediated cell killing (e.g., removal of active immune cells after an immune response) is effected by at least two major pathways. This includes Fas-mediated apoptosis (R6) and the release of granular perforin (which increases the permeability of the target cell membrane) and a group of proteases (e.g., serine protease granzyme B). Granzyme B can directly activate the target cell caspases (G8). 

Fig. 15.10. Pathways of DNA damage-mediated and p53-mediated apoptosis The presence of DNA lesions activates the ATM kinase and leads to an increase in p53 concentration. In a transcription-dependent pathway, p53 functions as a transcription activator of the bax gene. The increase in Bax protein facilitates release of cytochrome C from mitochondria and this serves as a trigger for activation of initiator and effector caspases. p53 also influences apoptosis by less well characterized ways, some of which are transcription independent.

Calcineurin. The calcineurin, or Ca2+-calmodulin dependent protein phosphatase (Aramburu et al., 2004) mediates apoptosis through at least two routes. First, this action can be achieved through steroid receptor Nur77 and CD95 ligand this pathway was found in lymphoid cells (Shi et al., 1989). Alternatively, calcineurin dephosphorylates a pro-apoptotic protein Bad (a member of Bcl-2 family), which in turn translocates into mitochondria and triggers release of cytochrome C and activation of caspases (Wang et al., 1999). 

Coleman ML, Sahai EA, Yeo M, Bosch M, Dewar A, Olson MF. Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I. Nat Cell Biol 2001 3 339-345. 

Figure 7.1 Activation of caspase 3-mediated apoptosis in skin cancer cells A-431 by EGCG. A. Control cells without EGCG exposure. B. Cells exposed to 50 pM for 24 h. C. EGCG dose-dependently induced the activation of caspase 3 in A-431 cells during a 24-h period. The caspase 3 activity measured by the cleavage of a substrate peptide increased by two-, six-, and ninefold compared to control when cells were exposed to 25, 50, and 100 pM of EGCG, respectively.

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