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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.

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.


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Morphological characteristics of untreated and tamoxifen treated HeLa cells under the light microscope. (a) Confluent control cells at 72 hours showing normal morphology with lamellipodium, prominent nucleus, and nucleoli in each cell × 400. (b) Tamoxifen treated cells (10 μg/ml) at 48 hours showing nuclear condensation, cell shrinkage, and enucleation (arrow) × 400. (c) Cells treated with tamoxifen(15 μg/ml) at 48 hours showing multinucleation and apoptotic bodies (arrows) ×900.
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Figure 2: Morphological characteristics of untreated and tamoxifen treated HeLa cells under the light microscope. (a) Confluent control cells at 72 hours showing normal morphology with lamellipodium, prominent nucleus, and nucleoli in each cell × 400. (b) Tamoxifen treated cells (10 μg/ml) at 48 hours showing nuclear condensation, cell shrinkage, and enucleation (arrow) × 400. (c) Cells treated with tamoxifen(15 μg/ml) at 48 hours showing multinucleation and apoptotic bodies (arrows) ×900.

Mentions: Untreated HeLa cells exhibited typical growth patterns and normal morphology (see Figure 2a). The leading edge of the cell is spread into a flattened “veil-like” projection called a lamellipodium, whereas the trailing end of the cell is narrowed into a tail. Each control cell had one distinct nucleus with several nucleoli. Light microscopic observations of treated HeLa cells showed shrinkage, nuclear condensation, and occasional enucleation (see Figure 2b). Multinucleation andapoptotic bodies, which are characteristic of programmed cell death (apoptosis), were also detected in treatment groups (see Figure 2c). Tamoxifen treatment at 10 μg/ml or higher exhibited elongated lamellipodia and many detached cells.Frequency of dead cells increased in abundance in 15 and 20 μg/ml tamoxifen treated groups even after 24 hours of exposure.


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)

Morphological characteristics of untreated and tamoxifen treated HeLa cells under the light microscope. (a) Confluent control cells at 72 hours showing normal morphology with lamellipodium, prominent nucleus, and nucleoli in each cell × 400. (b) Tamoxifen treated cells (10 μg/ml) at 48 hours showing nuclear condensation, cell shrinkage, and enucleation (arrow) × 400. (c) Cells treated with tamoxifen(15 μg/ml) at 48 hours showing multinucleation and apoptotic bodies (arrows) ×900.
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Related In: Results  -  Collection

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Figure 2: Morphological characteristics of untreated and tamoxifen treated HeLa cells under the light microscope. (a) Confluent control cells at 72 hours showing normal morphology with lamellipodium, prominent nucleus, and nucleoli in each cell × 400. (b) Tamoxifen treated cells (10 μg/ml) at 48 hours showing nuclear condensation, cell shrinkage, and enucleation (arrow) × 400. (c) Cells treated with tamoxifen(15 μg/ml) at 48 hours showing multinucleation and apoptotic bodies (arrows) ×900.
Mentions: Untreated HeLa cells exhibited typical growth patterns and normal morphology (see Figure 2a). The leading edge of the cell is spread into a flattened “veil-like” projection called a lamellipodium, whereas the trailing end of the cell is narrowed into a tail. Each control cell had one distinct nucleus with several nucleoli. Light microscopic observations of treated HeLa cells showed shrinkage, nuclear condensation, and occasional enucleation (see Figure 2b). Multinucleation andapoptotic bodies, which are characteristic of programmed cell death (apoptosis), were also detected in treatment groups (see Figure 2c). Tamoxifen treatment at 10 μg/ml or higher exhibited elongated lamellipodia and many detached cells.Frequency of dead cells increased in abundance in 15 and 20 μg/ml tamoxifen treated groups even after 24 hours of exposure.

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