ROS-triggered caspase 2 activation and feedback amplification loop in β-carotene-induced apoptosis

Prasad, Vandna; Chandele, Anmol; Jagtap, Jayashree C.; Kumar, Pranaw; Shastry, Padma

doi:10.1016/j.freeradbiomed.2006.03.009

Cited by 52 publications

(48 citation statements)

References 39 publications

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“…32 Lastly, the generation of reactive oxygen species (ROS), which occurs after irradiation, has recently been demonstrated to lead to the activation of caspase-2. 33 In conclusion, we report here essential data concerning the mechanisms involved in the IR-induced depletion of primordial follicle stock occurring after birth, which may serve to maintain genomic integrity. We demonstrate that following genotoxic stress, the disappearance of the follicular reserve involves an early caspase-2-dependent activation of the apoptotic mitochondrial pathway in quiescent oocytes.…”

Section: Discussionmentioning

confidence: 84%

Caspase-2 involvement during ionizing radiation-induced oocyte death in the mouse ovary

et al. 2006

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In mammals, the pool of primordial follicles at birth is determinant for female fertility. Exposure to IR during oogonia proliferation and the diplotene stages of ovarian development induced the virtual disappearance of primordial follicles in the postnatal ovary, while half the follicular reserve remained present after irradiation during the zygotene/pachytene stages. This sensitivity difference was correlated with the level of caspase-2 expression evaluated by immunohistochemistry. At the diplotene stage, Western blot and caspase activity analysis revealed that caspase-2 was activated 2 h after irradiation and a significant increase in the number of oocytes expressing cleaved caspase-9 and -3 occurred 6 h after treatment. Inhibition of caspase-2 activity prevented the cleavage of caspase-9 and partially prevented the loss of oocytes in response to irradiation. Taken together, our results show that caspase-2-dependent activation of the mitochondrial apoptotic pathway is one of the mechanisms involved in the genotoxic stress-induced depletion of the primordial follicle pool.

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Section: Discussionmentioning

confidence: 84%

Caspase-2 involvement during ionizing radiation-induced oocyte death in the mouse ovary

et al. 2006

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“…54,55 Second, it has been shown that reactive oxygen species are capable of activating caspase-2. 56 Interestingly, perifosine generates ROS in AML cells. 27 Experiments are currently underway in our laboratory to distinguish which of these two mechanisms is important in THP-1 cells.…”

Section: Discussionmentioning

confidence: 99%

Proapoptotic activity and chemosensitizing effect of the novel Akt inhibitor perifosine in acute myelogenous leukemia cells

et al. 2007

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The serine/threonine kinase Akt, a downstream effector of phosphatidylinositol 3-kinase (PI3K), is known to play an important role in antiapoptotic signaling and has been implicated in the aggressiveness of a number of different human cancers including acute myelogenous leukemia (AML). We have investigated the therapeutic potential of the novel Akt inhibitor, perifosine, on human AML cells. Perifosine is a synthetic alkylphospholipid, a new class of antitumor agents, which target plasma membrane and inhibit signal transduction networks. Perifosine was tested on THP-1 and MV 4-11 cell lines, as well as primary leukemia cells. Perifosine treatment induced cell death by apoptosis in AML cell lines. Perifosine caused Akt and ERK 1/2 dephosphorylation as well as caspase activation. In THP-1 cells, the proapoptotic effect of perifosine was partly dependent on the Fas/FasL system and c-jun-N-kinase activation. In MV 4-11 cells, perifosine downregulated phosphorylated Akt, but not phosphorylated FLT3. Moreover, perifosine reduced the clonogenic activity of AML, but not normal, CD34 þ cells, and markedly increased blast cell sensitivity to etoposide. Our findings indicate that perifosine, either alone or in combination with existing drugs, might be a promising therapeutic agent for the treatment of those AML cases characterized by upregulation of the PI3K-Akt survival pathway.

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“…Alternatively, caspase‐8 could be triggered by ROS, mediating the mitochondrial pathway and bypassing CD95/Fas engagement 25, 38, 39. It has also been reported the possibility of an interdependence of caspase‐2, ‐8, ‐9, and ‐3 in an apoptotic process mediated by ROS 17, 40. Once we also had mitochondrial transmembrane‐potential dissipation and increased ROS production, the apoptosis induced by AC‐1001 H3 likely occurred via the intrinsic pathway and caspase‐8 activation was induced by ROS.…”

Section: Discussionmentioning

confidence: 99%

AC‐1001 H3 CDR peptide induces apoptosis and signs of autophagy in vitro and exhibits antimetastatic activity in a syngeneic melanoma model

et al. 2016

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Antibody‐derived peptides modulate functions of the immune system and are a source of anti‐infective and antitumor substances. Recent studies have shown that they comprise amino acid sequences of immunoglobulin complementarity‐determining regions, but also fragments of constant regions. VH CDR3 of murine mAb AC‐1001 displays antimetastatic activities using B16F10‐Nex2 murine melanoma cells in a syngeneic model. The peptide was cytotoxic in vitro in murine and human melanoma cells inducing reactive oxygen species (ROS) and apoptosis by the intrinsic pathway. Signs of autophagy were also suggested by the increased expression of LC3/LC3II and Beclin 1 and by ultrastructural evidence. AC‐1001 H3 bound to both G‐ and F‐actin and inhibited tumor cell migration. These results are important evidence of the antitumor activity of Ig CDR‐derived peptides.

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ROS-triggered caspase 2 activation and feedback amplification loop in β-carotene-induced apoptosis

Cited by 52 publications

References 39 publications

Caspase-2 involvement during ionizing radiation-induced oocyte death in the mouse ovary

Caspase-2 involvement during ionizing radiation-induced oocyte death in the mouse ovary

Proapoptotic activity and chemosensitizing effect of the novel Akt inhibitor perifosine in acute myelogenous leukemia cells

AC‐1001 H3 CDR peptide induces apoptosis and signs of autophagy in vitro and exhibits antimetastatic activity in a syngeneic melanoma model

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