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Necrotic Effect versus Apoptotic Nature of Camptothecin in Human Cervical Cancer Cells

AUTHORS

Abbas Zare-Mirakabadi 1 , Ali Sarzaeem 2 , * , Saeed Moradhaseli 1 , Aida Sayad 3 , Masoud Negahdary 4

1 Dept. of Venomous Animals and Antivenom Production, Razi Vaccine and Serum Research Institute, Karaj, Iran

2 Dept. of Venomous Animals and Antivenom Production, Razi Vaccine and Serum Research Institute, Karaj; Dept. of Biology, Payam-e-Noor University, Tehran, Iran

3 Dept. of Biochemistry, Faculty of Medicine, Tarbiat Modares University, Tehran, Iran

4 Dept. of Biology, Payam-e-Noor University, Shiraz, Iran

How to Cite: Zare-Mirakabadi A, Sarzaeem A , Moradhaseli S, Sayad A, Negahdary M. Necrotic Effect versus Apoptotic Nature of Camptothecin in Human Cervical Cancer Cells, Int J Cancer Manag. 2012 ; 5(3):e80810.

ARTICLE INFORMATION

International Journal of Cancer Management: 5 (3); e80810
Published Online: September 30, 2012
Article Type: Research Article
Received: March 03, 2012
Accepted: May 15, 2012

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Abstract

Background: Functional defects in mitochondria are involved in the induction of cell death in cancer cells. The process of programmed cell death may occur through the mechanisms of apoptosis. Several potential lead molecules such as Camptothecin (CPT) and its analogues have been isolated from plants with anticancer effect. The aim of the present study was to understand the necrotic effect versus apoptotic nature of CPT in HeLa cancer cells.

Methods: The anti-proliferative activity of CPT was estimated through 3-(4, 5- Dimethyl Thiazol-2-yl)-2, 5-diphenyl Tetrazolium bromide (MTT) assay and DNA fragmentation analysis using gel electrophoresis. Lactate Dehydrogenase (LDH) activity and cell morphology were assessed under control and CPT exposed conditions to evaluate the necrotic effect of CPT.

Results: The results showed that CPT inhibited the proliferation of HeLa cells in a dose-dependent manner with an Inhibitory Concentration 50% (IC50) of 0.08±0.012 µg/ml. However the significant (p<0.05) increase happens in LDH activity at concentrations 1×10-1µg/ml and above. Morphological changes showed that CPT in low concentrations induced an apoptotic mechanism of cell death, such as cell shrinkage and characteristic rounding of dying cells, while at high concentrations showed necrosis changes. The characteristic DNA ladder formation of CPT-treated cells in agarose gel electrophoresis confirmed the results obtained by light microscopy and LDH assay.

Conclusion: Camptothecin as an anticancer drug may have anti-proliferative effect on HeLa cancer cells in low concentrations, through its nature of induction of apoptosis. The border line between necrotic effect and apoptotic nature of CPT in HeLa cancer cells has been found to be at concentration of 1×10-1 µg/ml.

Keywords

Cell death Camptothecin HeLa cells Necrosis Apoptosis

© 2012, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

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