| ACTX-8, a cytotoxic L-amino acid oxidase isolated from Agkistrodon acutus snake venom, induces apoptosis in Hela cervical cancer cells. | |
| | |
MedLine Citation:
|
PMID: 17275856 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
ACTX-8 is a protein isolated from Agkistrodon acutus snake venom in our laboratory. It demonstrates cytotoxic activity on various carcinoma cell lines in vitro. However, the mechanism by which ACTX-8 inhibits cell proliferation remains poorly understood. In this study the influence of ACTX-8 on the activation of apoptotic pathway in Hela cells was investigated. We demonstrated that cell death induced by ACTX-8 was concentration- and time-dependent. Apoptotic changes such as phosphatidyl serine externalization and DNA fragmentation were detected in ACTX-8-treated cells. Caspase activation and reactive oxygen species (ROS) production were involved in ACTX-8-induced apoptosis, but pan caspase inhibitor, z-VAD-fmk, could not inhibit cell death induced by ACTX-8 completely, which proved the existence of another pathway for ACTX-8-induced cell death. We found cytochrome c release into cytosol and mitochondrial membrane potential (MMP) dissipation in ACTX-8-treated cells, which indicated that mitochondrial pathway played a role in ACTX-8-induced cell apoptosis. The ratio of expression levels of pro- and anti-apoptotic Bcl-2 family members was not changed by ACTX-8 treatment. However Bad and Bax were translocated from cytosol into mitochondria, and the coimmunoprecipitation result indicated that in mitochondria Bak and Bcl-xL dissociation was followed by the binding of Bad and Bcl-xL. Taken together, the study indicated mitochondrial pathway played an important role in the ACTX-8-induced apoptosis, which was regulated by Bcl-2 family members. |
| | |
Authors:
|
Liang Zhang; Li-Jun Wei |
Related Documents
:
|
18344566 - Cysteine 62 of bax is critical for its conformational activation and its proapoptotic a... 19551546 - Enhancement of hyperthermia-induced apoptosis by sanazole in human lymphoma u937 cells. 11533046 - Free cholesterol loading of macrophages is associated with widespread mitochondrial dys... 14647446 - Induction of apoptosis by enediyne antibiotic calicheamicin thetaii proceeds through a ... 21478876 - Amelioration of sepsis by inhibiting sialidase-mediated disruption of the cd24-siglecg ... 21887476 - Inhibition of experimental auto-immune uveitis by the a3 adenosine receptor agonist cf101. |
Publication Detail:
|
Type: Journal Article Date: 2007-01-12 |
Journal Detail:
|
Title: Life sciences Volume: 80 ISSN: 0024-3205 ISO Abbreviation: Life Sci. Publication Date: 2007 Mar |
Date Detail:
|
Created Date: 2007-02-19 Completed Date: 2007-03-29 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0375521 Medline TA: Life Sci Country: England |
Other Details:
|
Languages: eng Pagination: 1189-97 Citation Subset: IM |
Affiliation:
|
School of Pharmacy, Soochow University, Soochow, Jiangsu Province, 215123, China. cpuzl@163.com |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Agkistrodon* Animals Antineoplastic Agents / pharmacology* Apoptosis / drug effects* Caspase 3 / antagonists & inhibitors, biosynthesis Caspase 9 / antagonists & inhibitors, biosynthesis Cell Fractionation Cell Survival / drug effects Crotalid Venoms / chemistry*, pharmacology Cytochromes c / metabolism DNA Fragmentation Dose-Response Relationship, Drug Drug Screening Assays, Antitumor Enzyme Activation Enzyme Inhibitors / pharmacology Female Hela Cells / pathology Humans Membrane Potential, Mitochondrial / drug effects Mitochondria / drug effects, metabolism Phosphatidylserines / metabolism Proto-Oncogene Proteins c-bcl-2 / metabolism Uterine Cervical Neoplasms / pathology* |
| Chemical | |
Reg. No./Substance:
|
0/ACTX-8 protein, Agkistrodon acutus; 0/Antineoplastic Agents; 0/Crotalid Venoms; 0/Enzyme Inhibitors; 0/Phosphatidylserines; 0/Proto-Oncogene Proteins c-bcl-2; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 9 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Detection of alpha7 nicotinic acetylcholine receptors with the aid of antibodies and toxins.
Next Document: Pharmacological characterization of receptor types mediating the dilator action of anandamide on blo...