Phthalocyanine 4 photodynamic therapy-induced apoptosis of mouse L5178Y-R cells results from a delayed but extensive release of cytochrome c from mitochondria

2001 ◽  
Vol 165 (1) ◽  
pp. 51-58 ◽  
Author(s):  
Song-Mao Chiu ◽  
Helen H. Evans ◽  
Minh Lam ◽  
Anna-Liisa Nieminen ◽  
Nancy L. Oleinick
Keyword(s):  
Photodynamic Therapy ◽  
Cytochrome C ◽  
Induced Apoptosis ◽  
Extensive Release

scholarly journals Autoregulatory Feedback Mechanism of P38MAPK/Caspase-8 in Photodynamic Therapy-Hydrophilic/Lipophilic Tetra-α-(4-carboxyphenoxy) Phthalocyanine Zinc-Induced Apoptosis of Human Hepatocellular Carcinoma Bel-7402 Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Yu Wang ◽  
Chunhui Xia ◽  
Wei Chen ◽  
Yuhang Chen ◽  
Yiyi Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Photodynamic Therapy ◽  
Membrane Potential ◽  
Cytochrome C ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Caspase 3 ◽  
Human Hepatocellular Carcinoma ◽  
Caspase 8 ◽  
Induced Apoptosis

Photodynamic therapy (PDT) is a novel and promising antitumor treatment. Our previous study showed that hydrophilic/lipophilic tetra-α-(4-carboxyphenoxy) phthalocyanine zinc- (TαPcZn-) mediated PDT (TαPcZn-PDT) inhibits the proliferation of human hepatocellular carcinoma Bel-7402 cells by triggering apoptosis and arresting cell cycle. However, mechanisms of TαPcZn-PDT-induced apoptosis of Bel-7402 cells have not been fully clarified. In the present study, therefore, effect of TαPcZn-PDT on apoptosis, P38MAPK, p-P38MAPK, Caspase-8, Caspase-3, Bcl-2, Bid, Cytochrome c, and mitochondria membrane potential in Bel-7402 cells without or with P38MAPK inhibitor SB203580 or Caspase-8 inhibitor Ac-IEFD-CHO was investigated by haematoxylin and eosin (HE) staining assay, flow cytometry analysis of annexin V-FITC/propidium iodide (PI) double staining cells and 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide (JC-1), and immunoblot assay. We found that TαPcZn-PDT resulted in apoptosis induction, activation of P38MAPK, Caspase-8, Caspase-3, and Bid, downregulation of Bcl-2, release of Cytochrome c from mitochondria, and disruption of mitochondrial membrane potential in TαPcZn-PDT-treated Bel-7402 cells. In contrast, SB203580 or Ac-IEFD-CHO attenuated induction of apoptosis, activation of P38MAPK, Caspase-8, Caspase-3, and Bid, downregulation of Bcl-2, release of Cytochrome c from mitochondria, and disruption of mitochondrial membrane potential in TαPcZn-PDT-treated Bel-7402 cells. Taken together, we conclude that Caspase-3, Bcl-2, Bid, and mitochondria are involved in autoregulatory feedback of P38MAPK/Caspase-8 during TαPcZn-PDT-induced apoptosis of Bel-7402 cells.

scholarly journals Analysis of redox regulation of cytochrome c-induced apoptosis in a cell-free system

1999 ◽  
Vol 6 (7) ◽  
pp. 683-688 ◽  
Author(s):  
Zhaohui Pan ◽  
David W Voehringer ◽  
Raymond E Meyn
Keyword(s):  
Cytochrome C ◽  
Redox Regulation ◽  
Free System ◽  
Cell Free System ◽  
A Cell ◽  
Induced Apoptosis

Prevention of TNF-α-induced apoptosis in polyamine-depleted IEC-6 cells is mediated through the activation of ERK1/2

2004 ◽  
Vol 286 (3) ◽  
pp. G479-G490 ◽  
Author(s):  
Sujoy Bhattacharya ◽  
Ramesh M. Ray ◽  
Leonard R. Johnson
Keyword(s):  
Epithelial Cells ◽  
Cytochrome C ◽  
Critical Role ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Cytochrome C Release ◽  
Erk Phosphorylation ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Jnk Activation

It has been documented that polyamines play a critical role in the regulation of apoptosis in intestinal epithelial cells. We have recently reported that protection from TNF-α/cycloheximide (CHX)-induced apoptosis in epithelial cells depleted of polyamines is mediated through the inactivation of a proapoptotic mediator, JNK. In this study, we addressed the involvement of the MAPK pathway in the regulation of apoptosis after polyamine depletion of IEC-6 cells. Polyamine depletion by α-difluromethylornithine (DFMO) resulted in the sustained activation of ERK in response to TNF-α/CHX treatment. Pretreatment of polyamine-depleted IEC-6 cells with a cell membrane-permeable MEK1/2 inhibitor, U-0126, significantly inhibited TNF-α/CHX-induced ERK phosphorylation and significantly increased DNA fragmentation, JNK activity, and caspase-3 activity in response to TNF-α/CHX. Moreover, the dose dependency of U-0126-mediated inhibition of TNF-α/ CHX-induced ERK phosphorylation correlated with the reversal of the antiapoptotic effect of DFMO. IEC-6 cells expressing constitutively active MEK1 had decreased TNF-α/CHX-induced JNK phosphorylation and were significantly protected from apoptosis. Conversely, a dominant-negative MEK1 resulted in high basal activation of JNK, cytochrome c release, and spontaneous apoptosis. Polyamine depletion of the dominant-negative MEK1 cells did not prevent JNK activation or cytochrome c release and failed to confer protection from both TNF-α/CHX and camptothecin-induced apoptosis. Finally, expression of a dominant-negative mutant of JNK significantly protected IEC-6 cells from TNF-α/CHX-induced apoptosis. These data indicate that polyamine depletion results in the activation of ERK, which inhibits JNK activation and protects cells from apoptosis.

Oligomycin and antimycin A prevent nitric oxide–induced apoptosis by blocking cytochrome C leakage

2004 ◽  
Vol 143 (3) ◽  
pp. 143-151 ◽  
Author(s):  
Naohiro Dairaku ◽  
Katsuaki Kato ◽  
Kennichi Honda ◽  
Tomoyuki Koike ◽  
Katsunori Iijima ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cytochrome C ◽  
Antimycin A ◽  
Induced Apoptosis

Liposomal ET-18-OCH3 Induces Cytochrome c-Mediated Apoptosis Independently of CD95 (APO-1/Fas) Signaling

Blood ◽  
1999 ◽  
Vol 94 (10) ◽  
pp. 3583-3592 ◽  
Author(s):  
Olivier Cuvillier ◽  
Eric Mayhew ◽  
Andrew S. Janoff ◽  
Sarah Spiegel
Keyword(s):  
Cytochrome C ◽  
Critical Role ◽  
Ether Lipid ◽  
Tumor Model ◽  
Model Systems ◽  
Triggered Release ◽  
Receptor System ◽  
Cd95 Ligand ◽  
Fas Signaling ◽  
Induced Apoptosis

ELL-12, a liposome formulation of the ether-lipid 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH3), is a nonmyelosuppressive antiproliferative agent that is more effective and less toxic than the ether lipid itself in tumor model systems. We found that ELL-12 induced apoptosis in Jurkat, H9, and U-937 cells that was preceded by activation of executioner caspases. In addition, ELL-12 triggered release of cytochrome c from mitochondria to the cytoplasm before caspase-9 activation. Apoptosis, activation of caspases, and cytochromec release were blocked by Bcl-xL overexpression in Jurkat T cells, suggesting a critical role for mitochondria in ELL-12–triggered cell death. Furthermore, ELL-12 had no effect on expression of CD95 ligand, and inhibition of the Fas signaling pathway with antagonistic anti-CD95 antibody did not affect apoptosis induced by ELL-12. Hence, ELL-12 could be a promising adjunct for the treatment of tumors in addition to myelosuppressive chemotherapeutic drugs and/or those that use the CD95-ligand/receptor system to trigger apoptosis.

scholarly journals Contribution of Mitochondrial Ion Channels to Chemo-Resistance in Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 761 ◽  
Author(s):  
Roberta Peruzzo ◽  
Ildiko Szabo
Keyword(s):  
Ion Channels ◽  
Cytochrome C ◽  
Cancer Cells ◽  
Cytochrome C Release ◽  
Drug Induced ◽  
Point Of No Return ◽  
Different Types ◽  
Subsequent Activation ◽  
Induced Apoptosis ◽  
Potential Efficiency

Mitochondrial ion channels are emerging oncological targets, as modulation of these ion-transporting proteins may impact on mitochondrial membrane potential, efficiency of oxidative phosphorylation and reactive oxygen production. In turn, these factors affect the release of cytochrome c, which is the point of no return during mitochondrial apoptosis. Many of the currently used chemotherapeutics induce programmed cell death causing damage to DNA and subsequent activation of p53-dependent pathways that finally leads to cytochrome c release from the mitochondrial inter-membrane space. The view is emerging, as summarized in the present review, that ion channels located in this organelle may account in several cases for the resistance that cancer cells can develop against classical chemotherapeutics, by preventing drug-induced apoptosis. Thus, pharmacological modulation of these channel activities might be beneficial to fight chemo-resistance of different types of cancer cells.

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