Limits...
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.

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

Growth inhibitory effect of tamoxifen on HeLa cells. Percent ofcontrol number of viable cells/ml as a function of time after tamoxifen treatment in 6-well culture plates.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC129061&req=5

Figure 1: Growth inhibitory effect of tamoxifen on HeLa cells. Percent ofcontrol number of viable cells/ml as a function of time after tamoxifen treatment in 6-well culture plates.

Mentions: HeLa cell growth inhibition was both time and drug-concentration dependent in an inverse relationship in excess of 5 μg/ml (see Figure 1). A minimum growth inhibitory effect was seen at 3 and5 μg/ml tamoxifen treatments. At 5 μg/ml, the number of cells/ml initially decreased (about 65% of the control) and then followed a trend similar to the 3 μg/ml treated group, but at a slower growth rate after 24 hours. The number of viable HeLa cells treated with 10 μg/ml, compared to the control, began to decrease(45%) after only 24 hours and continued to decrease to 20% of the control by 96 hours. A drastic reduction in viable cell number was seen by 24 hours of tamoxifen treatment at 15 and 20 μg/ml and resulted in complete death by 96 hours (see Figure 1).


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)

Growth inhibitory effect of tamoxifen on HeLa cells. Percent ofcontrol number of viable cells/ml as a function of time after tamoxifen treatment in 6-well culture plates.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Growth inhibitory effect of tamoxifen on HeLa cells. Percent ofcontrol number of viable cells/ml as a function of time after tamoxifen treatment in 6-well culture plates.
Mentions: HeLa cell growth inhibition was both time and drug-concentration dependent in an inverse relationship in excess of 5 μg/ml (see Figure 1). A minimum growth inhibitory effect was seen at 3 and5 μg/ml tamoxifen treatments. At 5 μg/ml, the number of cells/ml initially decreased (about 65% of the control) and then followed a trend similar to the 3 μg/ml treated group, but at a slower growth rate after 24 hours. The number of viable HeLa cells treated with 10 μg/ml, compared to the control, began to decrease(45%) after only 24 hours and continued to decrease to 20% of the control by 96 hours. A drastic reduction in viable cell number was seen by 24 hours of tamoxifen treatment at 15 and 20 μg/ml and resulted in complete death by 96 hours (see Figure 1).

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