In vitro investigations on the toxicity and cell death induced by tamoxifen on two non-breast cancer cell types

Valdellon, J. A.; Brown, K. A.; Majumdar, Shyamal K.

In vitro investigations on the toxicity and cell death induced by tamoxifen on two non-breast cancer cell types

Abstract

Tamoxifen, a potent anticancer agent known to interrupt the enhanced estrogen activity of malignant mammary gland cells, was
recently approved by the Food and Drug Administration (FDA) for the treatment of breast cancer. In this investigation, the toxic
effects of tamoxifen were evaluated through cell multiplication, and cytological, surface ultrastructural, and biochemical studies
on human cervical carcinoma cells (HeLa) and/or murine erythroleukemic (MEL) cells (BB-88). Tamoxifen treatment demonstrated
an inhibitory effect on HeLa cell multiplication at lower concentrations and toxicity at higher concentrations and longer
treatment durations. The drug also triggered morphological and biochemical changes as revealed by light microscopy, scanning
electron microscopy (SEM), fluorescence microscopy, Nucleosome ELISA, and the DNA smear pattern. Cytological observations
showed nuclear condensation, cell shrinkage, multinucleation, and apoptotic bodies. Surface ultrastructure of tamoxifen treated
cells examined under the SEM revealed abnormalities such as membrane blebbing, holes, and cytoplasmic extrusions, all of which
are characteristics of programmed cell death (apoptosis). Redistribution of the membrane phospholipid phosphatidylserine (PS)
from the protoplasmic surface of the plasma membrane to the cell surface was identified using annexin V-enhanced green fluorescent
protein (EGFP) in tamoxifen treated MEL BB-88 cells, a general feature of cells undergoing apoptosis. Tamoxifen treated
cells demonstrated internucleosomal damages of the genomic DNA and DNA fragmentations, evidenced by an increase in free
nucleosomes, and distinctive DNA smear patterns on the agarose gel.

Title	In vitro investigations on the toxicity and cell death induced by tamoxifen on two non-breast cancer cell types
Creator	Valdellon, J. A.
	Brown, K. A.
	Majumdar, Shyamal K.
Publisher	Journal of Biomedicine and Biotechnology
Academic Department	Biology
Division	Natural Sciences
Organization	Lafayette College
Date Issued	2001
Date Available	2015-06-05T15:53:44Z
Type	Article
Language	English
Bibliographic Citation	Majumdar, S. K., J. A. Valdellon and K. A. Brown (2001) "In vitro investigations on the toxicity and cell death induced by tamoxifen on two non-breast cancer cell types." Journal of Biomedicine and Biotechnology 1(3): 99–107.
Standard Identifier	Handle 10385/1985
Standard Identifier	DOI 10.1155/S1110724301000316
Permalink	http://hdl.handle.net/10385/1985
Rights Statement	In Copyright
Rights Holders	Hindawi Publishing Corporation