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Synthesis, structural characterization, and anticancer activity of a monobenzyltin compound against MCF-7 breast cancer cells.

Fani S, Kamalidehghan B, Lo KM, Hashim NM, Chow KM, Ahmadipour F - Drug Des Devel Ther (2015)

Bottom Line: A significant increase of lactate dehydrogenase release in treated cells was observed via fluorescence analysis.Luminescent analysis showed significant growth in intracellular reactive oxygen species production after treatment.DNA fragmentation was observed as a characteristic of apoptosis in treated cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

ABSTRACT
A new monoorganotin Schiff base compound, [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, (compound C1), was synthesized, and its structural features were investigated by spectroscopic techniques and single-crystal X-ray diffractometry. Compound C1 was exposed to several human cancer cell lines, including breast adenocarcinoma cell lines MCF-7 and MDA-MB-231, ovarian adenocarcinoma cell lines Skov3 and Caov3, and prostate cancer cell line PC3, in order to examine its cytotoxic effect for different forms of cancer. Human hepatic cell line WRL-68 was used as a normal cell line. We concentrated on the MCF-7 cell line to detect possible underlying mechanism involvement of compound C1. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed the strongest cytotoxicity of compound C1 against MCF-7 cells, with a half maximal inhibitory concentration (IC50) value of 2.5±0.50 μg/mL after 48 hours treatment. The IC50 value was >30 μg/mL in WRL-68 cells. Induced antiproliferative activity of compound C1 for MCF-7 cells was further confirmed by lactate dehydrogenase, reactive oxygen species, acridine orange/propidium iodide staining, and DNA fragmentation assays. A significant increase of lactate dehydrogenase release in treated cells was observed via fluorescence analysis. Luminescent analysis showed significant growth in intracellular reactive oxygen species production after treatment. Morphological changes of necrosis and early and late apoptosis stages were observed in treated cells after staining with acridine orange/propidium iodide. DNA fragmentation was observed as a characteristic of apoptosis in treated cells. Results of the present study obviously reveal potential cytotoxic effects of compound C1 against human breast cancer MCF-7 cells.

No MeSH data available.


Related in: MedlinePlus

Significant LDH release in the cell culture medium after exposure of MCF-7 cells to the 1.25, 2.5, 5, and 10 μg/mL concentrations of benzyltin compound C1 for (A) 24 hours and (B) 48 hours.Notes: Data are mean ± SD and representative of three independent experiments. Each independent experiment was performed in triplicate for each treatment group. The statistical significance is expressed as *P<0.05.Abbreviations: C1, compound 1 [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride; LDH, lactate dehydrogenase; SD, standard deviation.
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f5-dddt-9-6191: Significant LDH release in the cell culture medium after exposure of MCF-7 cells to the 1.25, 2.5, 5, and 10 μg/mL concentrations of benzyltin compound C1 for (A) 24 hours and (B) 48 hours.Notes: Data are mean ± SD and representative of three independent experiments. Each independent experiment was performed in triplicate for each treatment group. The statistical significance is expressed as *P<0.05.Abbreviations: C1, compound 1 [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride; LDH, lactate dehydrogenase; SD, standard deviation.

Mentions: LDH is a cytosolic enzyme which oxidizes L-lactate to pyruvate. Leakage of LDH from cytoplasm in the medium is an indicator that there is change in plasma membrane permeability or incidence of apoptosis or necrosis. To investigate the impact of benzyltin compound C1 on LDH activity, MCF-7 cells were treated with different concentrations of compound for a period of 24 and 48 hours. The results demonstrate a significant induction of LDH rise in cells treated with IC50 and higher concentrations of compound C1 after 48 hours’ treatment (P<0.05). Cells treated for 24 hours showed similar behavior at concentrations of 5 and 10 μg/mL. However, an increase in LDH release was not statistically significant in cells treated with compound C1 for 24 hours at IC50 (Figure 5).


Synthesis, structural characterization, and anticancer activity of a monobenzyltin compound against MCF-7 breast cancer cells.

Fani S, Kamalidehghan B, Lo KM, Hashim NM, Chow KM, Ahmadipour F - Drug Des Devel Ther (2015)

Significant LDH release in the cell culture medium after exposure of MCF-7 cells to the 1.25, 2.5, 5, and 10 μg/mL concentrations of benzyltin compound C1 for (A) 24 hours and (B) 48 hours.Notes: Data are mean ± SD and representative of three independent experiments. Each independent experiment was performed in triplicate for each treatment group. The statistical significance is expressed as *P<0.05.Abbreviations: C1, compound 1 [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride; LDH, lactate dehydrogenase; SD, standard deviation.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664434&req=5

f5-dddt-9-6191: Significant LDH release in the cell culture medium after exposure of MCF-7 cells to the 1.25, 2.5, 5, and 10 μg/mL concentrations of benzyltin compound C1 for (A) 24 hours and (B) 48 hours.Notes: Data are mean ± SD and representative of three independent experiments. Each independent experiment was performed in triplicate for each treatment group. The statistical significance is expressed as *P<0.05.Abbreviations: C1, compound 1 [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride; LDH, lactate dehydrogenase; SD, standard deviation.
Mentions: LDH is a cytosolic enzyme which oxidizes L-lactate to pyruvate. Leakage of LDH from cytoplasm in the medium is an indicator that there is change in plasma membrane permeability or incidence of apoptosis or necrosis. To investigate the impact of benzyltin compound C1 on LDH activity, MCF-7 cells were treated with different concentrations of compound for a period of 24 and 48 hours. The results demonstrate a significant induction of LDH rise in cells treated with IC50 and higher concentrations of compound C1 after 48 hours’ treatment (P<0.05). Cells treated for 24 hours showed similar behavior at concentrations of 5 and 10 μg/mL. However, an increase in LDH release was not statistically significant in cells treated with compound C1 for 24 hours at IC50 (Figure 5).

Bottom Line: A significant increase of lactate dehydrogenase release in treated cells was observed via fluorescence analysis.Luminescent analysis showed significant growth in intracellular reactive oxygen species production after treatment.DNA fragmentation was observed as a characteristic of apoptosis in treated cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

ABSTRACT
A new monoorganotin Schiff base compound, [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, (compound C1), was synthesized, and its structural features were investigated by spectroscopic techniques and single-crystal X-ray diffractometry. Compound C1 was exposed to several human cancer cell lines, including breast adenocarcinoma cell lines MCF-7 and MDA-MB-231, ovarian adenocarcinoma cell lines Skov3 and Caov3, and prostate cancer cell line PC3, in order to examine its cytotoxic effect for different forms of cancer. Human hepatic cell line WRL-68 was used as a normal cell line. We concentrated on the MCF-7 cell line to detect possible underlying mechanism involvement of compound C1. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed the strongest cytotoxicity of compound C1 against MCF-7 cells, with a half maximal inhibitory concentration (IC50) value of 2.5±0.50 μg/mL after 48 hours treatment. The IC50 value was >30 μg/mL in WRL-68 cells. Induced antiproliferative activity of compound C1 for MCF-7 cells was further confirmed by lactate dehydrogenase, reactive oxygen species, acridine orange/propidium iodide staining, and DNA fragmentation assays. A significant increase of lactate dehydrogenase release in treated cells was observed via fluorescence analysis. Luminescent analysis showed significant growth in intracellular reactive oxygen species production after treatment. Morphological changes of necrosis and early and late apoptosis stages were observed in treated cells after staining with acridine orange/propidium iodide. DNA fragmentation was observed as a characteristic of apoptosis in treated cells. Results of the present study obviously reveal potential cytotoxic effects of compound C1 against human breast cancer MCF-7 cells.

No MeSH data available.


Related in: MedlinePlus