Rapid induction of mitochondrial events and caspase-independent apoptosis in Survivin-targeted melanoma cells

Liu, Tong; Brouha, Brook; Grossman, Douglas

doi:10.1038/sj.onc.1206978

Cited by 164 publications

(151 citation statements)

References 61 publications

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“…Consistent with these reports, it has been shown that apoptotic cell death triggered by downregulation of survivin could also be involved in both caspase-dependent and caspase-independent pathways (Shankar et al, 2001;Li, 2003;Liu et al, 2004).…”

Section: Discussionsupporting

confidence: 72%

Differential regulation of survivin expression and apoptosis by vitamin D3 compounds in two isogenic MCF-7 breast cancer cell sublines

Ling

Huang

et al. 2004

Oncogene

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Although both the antiapoptotic function of survivin and vitamin D 3 (VD3)-mediated cell growth inhibition and apoptosis have been extensively studied, it is not known whether survivin plays a role in VD3 compound-mediated cell growth inhibition and apoptosis induction. Using an isogenic model of MCF-7 breast adenocarcinoma cells (MCF-7E and MCF-7L sublines that are sensitive and resistant to VD3 compounds), we found that VD3 compounds effectively downregulated survivin in VD3-sensitive MCF-7E cells, which was associated with VD3-induced apoptosis. In contrast, VD3 compounds failed to downregulate survivin in VD3-resistant MCF-7L cells, which showed resistant to VD3-induced apoptosis. However, inhibition of survivin expression by small interfering RNA (siRNA) induced cell death per se and further sensitized VD3-induced apoptosis in MCF-7L cells, indicating that the inability of these cells to respond to VD3 is due to the failure to downregulate survivin. Forced expression of survivin not only blocked VD3-mediated G1 cell accumulation but also increased S and G2/M cell populations. VD3 treatment rapidly triggered the activation of p38 MAPK signaling in MCF-7E cells but not in MCF-7L cells. Moreover, inhibition of p38 activation diminished VD3-mediated survivin inhibition and partially rescued VD3-induced cell death. We further showed that VD3 increased the expression of TGFb1 and TGFb receptor 2, and that blocking the function of TGFb receptor 2 diminished VD3 compound-mediated survivin downregulation. Thus, we propose that the VD3 compound-induced growth inhibition and apoptosis induction are at least partially dependent on survivin downregulation via VD3-induced TGFb signaling and the activation of p38 MAPK pathway. Targeting survivin through these pathways may lead to novel applications for cancer therapeutics.

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Section: Discussionsupporting

confidence: 72%

Differential regulation of survivin expression and apoptosis by vitamin D3 compounds in two isogenic MCF-7 breast cancer cell sublines

Ling

Huang

et al. 2004

Oncogene

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“…Actually, the existence of functional survivincaspase complexes initially described is now controversial, as survivin lacks structural motifs that in other IAPs (for example, XIAP) mediated caspase binding. 32 But survivin may mediate apoptosis inhibition through interaction with proapoptotic factors such as the IAP inhibitor SMAC/Diablo, 33 the apoptosis-inducing factor AIF 34 or through subcellular compartmentalization in mitochondria. 35 Whether survivin exerts its inhibitory effect on caspase activity by direct or indirect mechanisms in myeloma cells is currently under investigation.…”

Section: Discussionmentioning

confidence: 99%

Significant impact of survivin on myeloma cell growth

et al. 2007

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Survivin is a fascinating member of the inhibitor of apoptosis protein (IAP) family with its dual roles in mitosis and apoptosis, and emerges as an attractive target for cancer therapy. Multiple myeloma (MM) is a plasma cell malignancy, characterized by deregulated proliferation, cell-death processes and fatal outcome. We thus investigated survivin expression in myeloma cells and its role in MM biology to evaluate its potential interest as a target in MM treatment. Our results describe the cancerspecific overexpression of survivin in myeloma cells and show a significant correlation between survivin expression at protein level and clinical course of MM. Moreover, survivin knockdown by RNA interference led to growth rate inhibition of myeloma cells related to apoptosis induction and deep cell-cycle disruption. Finally, survivin knockdown sensitized myeloma cells to conventional anti-myeloma agents. Altogether, these data argue for the interest to evaluate survivin antagonists in MM treatment.

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“…Finally downregulation of AIF expression by AIF-siRNA diminished A3D8-induced cell death suggesting that AIF is required for CD44-induced in HEL cells. Recent studies have suggested that AIF is a central mediator of relevant experimental models of cell death (Corbiere et al, 2004;Kang et al, 2004;Liu et al, 2004a;Cheung et al, 2005;Ishitsuka et al, 2005;Park et al, 2005). However, AIF is a janus protein with a vital role in cells via its redox activity, and a lethal role by participating to chromatinolysis and chromatin condensation once translocated to the nucleus (Lipton and Bossy-Wetzel, 2002;Vahsen et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

CD44 ligation induces caspase-independent cell death via a novel calpain/AIF pathway in human erythroleukemia cells

et al. 2006

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Ligation of the cell surface molecule CD44 by anti-CD44 monoclonal antibodies (mAbs) has been shown to induce cell differentiation, cell growth inhibition and in some cases, apoptosis in myeloid leukemic cells. We report, herein, that exposure of human erythroleukemic HEL cells to the anti-CD44 mAb A3D8 resulted in cell growth inhibition followed by caspase-independent apoptosis-like cell death. This process was associated with the disruption of mitochondrial membrane potential (DWm), the mitochondrial release of apoptosis-inducing factor (AIF), but not of cytochrome c, and the nuclear translocation of AIF. All these effects including cell death, loss of mitochondrial DWm and AIF release were blocked by pretreatment with the poly (ADP-ribose) polymerase inhibitor isoquinoline. A significant protection against cell death was also observed by using small interfering RNA for AIF. Moreover, we show that calpain protease was activated before the appearance of apoptosis, and that calpain inhibitors or transfection of calpain-siRNA decrease A3D8-induced cell death, and block AIF release. These data suggest that CD44 ligation triggers a novel caspaseindependent cell death pathway via calpain-dependent AIF release in erythroleukemic HEL cells.

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Rapid induction of mitochondrial events and caspase-independent apoptosis in Survivin-targeted melanoma cells

Cited by 164 publications

References 61 publications

Differential regulation of survivin expression and apoptosis by vitamin D3 compounds in two isogenic MCF-7 breast cancer cell sublines

Differential regulation of survivin expression and apoptosis by vitamin D3 compounds in two isogenic MCF-7 breast cancer cell sublines

Significant impact of survivin on myeloma cell growth

CD44 ligation induces caspase-independent cell death via a novel calpain/AIF pathway in human erythroleukemia cells

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