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In Vitro Investigations on the Toxicity and Cell Death Induced by Tamoxifen on Two Non-Breast Cancer Cell Types.

Majumdar SK, Valdellon JA, Brown KA - J. Biomed. Biotechnol. (2001)

Bottom Line: Tamoxifen treatment demonstrated an inhibitory effect on HeLa cell multiplication at lower concentrations and toxicity at higher concentrations and longer treatment durations.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.

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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.

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Degradation of chromatin into free nucleosomes of HeLa cells treated with10 μg/ml tamoxifen (black bars) compared to the control (gray bars), detected by the Nucleosome ELISA assay. Absorbance (450 nm) is a function of time after the drug treatment. Ten hour treatment period is significantly different from the control.
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Figure 6: Degradation of chromatin into free nucleosomes of HeLa cells treated with10 μg/ml tamoxifen (black bars) compared to the control (gray bars), detected by the Nucleosome ELISA assay. Absorbance (450 nm) is a function of time after the drug treatment. Ten hour treatment period is significantly different from the control.

Mentions: Tamoxifen treatment (10 μg/ml) of HeLa cells for 4, 6, and 10 hours yielded a higher absorbance than their respective controls (see Figure 6). A trend was identified that showed an increase in absorbance among the tamoxifen treatedlysates samples indicating an increase in the degradation of genomic chromatin into free nucleosomes. The increases in absorbance for the 4 and 6 hours tamoxifen treatments, compared to their corresponding controls, were not significantly different. However, the increase in absorbance for the 10 hours treatment group was statistically significant (ANOVA, P < 0.05).


In Vitro Investigations on the Toxicity and Cell Death Induced by Tamoxifen on Two Non-Breast Cancer Cell Types.

Majumdar SK, Valdellon JA, Brown KA - J. Biomed. Biotechnol. (2001)

Degradation of chromatin into free nucleosomes of HeLa cells treated with10 μg/ml tamoxifen (black bars) compared to the control (gray bars), detected by the Nucleosome ELISA assay. Absorbance (450 nm) is a function of time after the drug treatment. Ten hour treatment period is significantly different from the control.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC129061&req=5

Figure 6: Degradation of chromatin into free nucleosomes of HeLa cells treated with10 μg/ml tamoxifen (black bars) compared to the control (gray bars), detected by the Nucleosome ELISA assay. Absorbance (450 nm) is a function of time after the drug treatment. Ten hour treatment period is significantly different from the control.
Mentions: Tamoxifen treatment (10 μg/ml) of HeLa cells for 4, 6, and 10 hours yielded a higher absorbance than their respective controls (see Figure 6). A trend was identified that showed an increase in absorbance among the tamoxifen treatedlysates samples indicating an increase in the degradation of genomic chromatin into free nucleosomes. The increases in absorbance for the 4 and 6 hours tamoxifen treatments, compared to their corresponding controls, were not significantly different. However, the increase in absorbance for the 10 hours treatment group was statistically significant (ANOVA, P < 0.05).

Bottom Line: Tamoxifen treatment demonstrated an inhibitory effect on HeLa cell multiplication at lower concentrations and toxicity at higher concentrations and longer treatment durations.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.

View Article: PubMed Central - HTML - PubMed

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.

No MeSH data available.


Related in: MedlinePlus