Abstract | AIM: To examine the effect of venom from the spider Macrothele raven on cell proliferation and cytotoxicity in human cervical carcinoma, HeLa cells. METHODS: Morphological and biochemical signs of apoptosis appeared using acridine orange- ethidium bromide (AO/EB) staining. Marked morphological changes in HeLa cells after treatment with spider venom were observed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Cell proliferation and cytotoxicity were determined by [methyl-3H] thymidine assay ([3H]TdR) and lactate dehydrogenase (LDH) release, respectively. DNA fragmentation and cell cycle distribution were monitored using flow cytometry. In addition, Western blot analysis was used to evaluate the level of caspase-3 expression. In vivo examination of the inhibition of the size of tumors in nude mice treated with spider venom was measured. RESULTS: Marked morphological changes were observed using AO/EB staining, SEM and TEM assay. Spider venom at concentrations of 10-40 mg/L caused dose- and time-dependent inhibition of HeLa cell proliferation. The ratio of apoptosis and necrosis increased. The activity of caspase-3 was upregulated after spider venom treatment. In vivo study of tumor size revealed that tumors significantly decreased in size from controls to tumors treated for 3 weeks with spider venom (P<0.05). CONCLUSION: The inhibition of HeLa cells by the venom of the spider Macrothele raveni was carried out in three ways: induction of apoptosis, necrosis of toxicity damage and direct lysis. Spider venom is a novel anti- tumor material both in vitro and in vivo.
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Authors | Li Gao, Bao-en Shan, Jing Chen, Jian-hui Liu, Da-xiang Song, Bao-cheng Zhu |
Journal | Acta pharmacologica Sinica
(Acta Pharmacol Sin)
Vol. 26
Issue 3
Pg. 369-76
(Mar 2005)
ISSN: 1671-4083 [Print] United States |
PMID | 15715936
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Spider Venoms
- CASP3 protein, human
- Casp3 protein, mouse
- Caspase 3
- Caspases
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Caspase 3
- Caspases
(metabolism)
- Cell Cycle
(drug effects)
- Cell Proliferation
(drug effects)
- Dose-Response Relationship, Drug
- Female
- HeLa Cells
- Humans
- Mice
- Mice, Nude
- Neoplasm Transplantation
- Spider Venoms
(pharmacology)
- Uterine Cervical Neoplasms
(pathology)
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