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

SEM micrographs of surface ultrastructural characteristics of HeLa cells treated with and without tamoxifen. (a) Cell surface characteristics of 48 hours untreated HeLa cells showing numerous microvilli on the cell surface and lamellipodia extensions (L) (× 1500). (b) Tamoxifen treated HeLa cells (48 hours, 5 μg/ml) exhibiting cell surface blebbing (B) and narrowing of cells with elongated and shortened lamellipodia (L). Cell detachment is visible (× 1800). (c) 48 hours treated (15 μg/ml) HeLa cells depicting many blebs or apoptotic bodies (B) on the cell surface, broken lamellipodia, and cytoplasmic extrusions (E). Cell shrinkage and detachment are evident (× 1500).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC129061&req=5

Figure 4: SEM micrographs of surface ultrastructural characteristics of HeLa cells treated with and without tamoxifen. (a) Cell surface characteristics of 48 hours untreated HeLa cells showing numerous microvilli on the cell surface and lamellipodia extensions (L) (× 1500). (b) Tamoxifen treated HeLa cells (48 hours, 5 μg/ml) exhibiting cell surface blebbing (B) and narrowing of cells with elongated and shortened lamellipodia (L). Cell detachment is visible (× 1800). (c) 48 hours treated (15 μg/ml) HeLa cells depicting many blebs or apoptotic bodies (B) on the cell surface, broken lamellipodia, and cytoplasmic extrusions (E). Cell shrinkage and detachment are evident (× 1500).

Mentions: Control HeLa cells are flattened in shape and show numerous microvilli on the cell surface with extending lamellipodia and membrane connections (see Figure 4a). Occasional presence of rounded cells and blebbings on the cell surface are characteristics of HeLa cells in culture. In contrast, treated HeLa cells exhibited shrinkage and narrowing of lamellipodia with blunt microvilli. Compared to control cells, the tamoxifen treated cells produced many detached osmiophilic electron dense cells with conspicuous blebs, or apoptotic like bodies on the cell surface (see Figures 4b and 4c).


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)

SEM micrographs of surface ultrastructural characteristics of HeLa cells treated with and without tamoxifen. (a) Cell surface characteristics of 48 hours untreated HeLa cells showing numerous microvilli on the cell surface and lamellipodia extensions (L) (× 1500). (b) Tamoxifen treated HeLa cells (48 hours, 5 μg/ml) exhibiting cell surface blebbing (B) and narrowing of cells with elongated and shortened lamellipodia (L). Cell detachment is visible (× 1800). (c) 48 hours treated (15 μg/ml) HeLa cells depicting many blebs or apoptotic bodies (B) on the cell surface, broken lamellipodia, and cytoplasmic extrusions (E). Cell shrinkage and detachment are evident (× 1500).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: SEM micrographs of surface ultrastructural characteristics of HeLa cells treated with and without tamoxifen. (a) Cell surface characteristics of 48 hours untreated HeLa cells showing numerous microvilli on the cell surface and lamellipodia extensions (L) (× 1500). (b) Tamoxifen treated HeLa cells (48 hours, 5 μg/ml) exhibiting cell surface blebbing (B) and narrowing of cells with elongated and shortened lamellipodia (L). Cell detachment is visible (× 1800). (c) 48 hours treated (15 μg/ml) HeLa cells depicting many blebs or apoptotic bodies (B) on the cell surface, broken lamellipodia, and cytoplasmic extrusions (E). Cell shrinkage and detachment are evident (× 1500).
Mentions: Control HeLa cells are flattened in shape and show numerous microvilli on the cell surface with extending lamellipodia and membrane connections (see Figure 4a). Occasional presence of rounded cells and blebbings on the cell surface are characteristics of HeLa cells in culture. In contrast, treated HeLa cells exhibited shrinkage and narrowing of lamellipodia with blunt microvilli. Compared to control cells, the tamoxifen treated cells produced many detached osmiophilic electron dense cells with conspicuous blebs, or apoptotic like bodies on the cell surface (see Figures 4b and 4c).

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