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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.


Related in: MedlinePlus

Surface ultrastructural characteristics of BB-88 cells treated with or without tamoxifen as depicted under the SEM. (a) Control BB-88 cells at 48 hours (× 2400). (b) Tamoxifen treated BB-88 cells (24 hours,10 μg/ml) showing clumping, cell shrinkage, and membrane blebbing (B) (× 3000). (c) BB-88 cells treated with tamoxifen (48 hours, 10 μg/ml) showing clumping, cell membrane blebbing (B), holes (H), and cytoplasmic extrusions (E) (× 3500).
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Figure 3: Surface ultrastructural characteristics of BB-88 cells treated with or without tamoxifen as depicted under the SEM. (a) Control BB-88 cells at 48 hours (× 2400). (b) Tamoxifen treated BB-88 cells (24 hours,10 μg/ml) showing clumping, cell shrinkage, and membrane blebbing (B) (× 3000). (c) BB-88 cells treated with tamoxifen (48 hours, 10 μg/ml) showing clumping, cell membrane blebbing (B), holes (H), and cytoplasmic extrusions (E) (× 3500).

Mentions: Surface ultrastructure of tamoxifen treated cells, examined with the scanning electron microscope, revealed distinct morphological changes when exposed to tamoxifen. Exponentially growing (24 and 48 hours) untreated BB-88 cells are spherical in shape with a few blebs scattered over the intact cell membrane (see Figure 3a). Treated BB-88 cells at 24 and 48 hours were distorted in shape and exhibited clumping. Abnormalities such as cell shrinkage, severe membrane blebbing (see Figure 3b), holes, and cytoplasmic extrusions (see Figure 3c) were detected in the treatment groups.


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)

Surface ultrastructural characteristics of BB-88 cells treated with or without tamoxifen as depicted under the SEM. (a) Control BB-88 cells at 48 hours (× 2400). (b) Tamoxifen treated BB-88 cells (24 hours,10 μg/ml) showing clumping, cell shrinkage, and membrane blebbing (B) (× 3000). (c) BB-88 cells treated with tamoxifen (48 hours, 10 μg/ml) showing clumping, cell membrane blebbing (B), holes (H), and cytoplasmic extrusions (E) (× 3500).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Surface ultrastructural characteristics of BB-88 cells treated with or without tamoxifen as depicted under the SEM. (a) Control BB-88 cells at 48 hours (× 2400). (b) Tamoxifen treated BB-88 cells (24 hours,10 μg/ml) showing clumping, cell shrinkage, and membrane blebbing (B) (× 3000). (c) BB-88 cells treated with tamoxifen (48 hours, 10 μg/ml) showing clumping, cell membrane blebbing (B), holes (H), and cytoplasmic extrusions (E) (× 3500).
Mentions: Surface ultrastructure of tamoxifen treated cells, examined with the scanning electron microscope, revealed distinct morphological changes when exposed to tamoxifen. Exponentially growing (24 and 48 hours) untreated BB-88 cells are spherical in shape with a few blebs scattered over the intact cell membrane (see Figure 3a). Treated BB-88 cells at 24 and 48 hours were distorted in shape and exhibited clumping. Abnormalities such as cell shrinkage, severe membrane blebbing (see Figure 3b), holes, and cytoplasmic extrusions (see Figure 3c) were detected in the treatment groups.

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