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

Abbas Zare-Mirakabadi; Ali  Sarzaeem; Saeed Moradhaseli; Aida Sayad; Masoud Negahdary

International Journal of Cancer Management

The Official Journal of Cancer Research Center (CRC), Shahid Beheshti University of Medical Sciences

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

Author(s):

Abbas Zare-Mirakabadi¹,

Ali Sarzaeem^2,*,

Saeed Moradhaseli¹,

Aida Sayad³,

Masoud Negahdary⁴

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

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

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

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

International Journal of Cancer Management:Vol. 5, issue 3; e80810

Published online:Sep 30, 2012

Article type:Research Article

Received:Mar 03, 2012

Accepted:May 15, 2012

How to Cite:Abbas Zare-MirakabadiAli SarzaeemSaeed MoradhaseliAida SayadMasoud NegahdaryNecrotic Effect versus Apoptotic Nature of Camptothecin in Human Cervical Cancer Cells.Int J Cancer Manag.5(3):e80810.

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.

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