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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

ROS generation in treated MCF-7 cells.Notes: ROS generation as determined by DCFH-DA fluorescence intensity after 1.25, 2.5, 5, and 10 μg/mL of benzyltin compound C1 exposure at (A) 24 hours and (B) 48 hours. 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; DCFH-DA, 2′,7′-dichlorofluorescein diacetate; ROS, reactive oxygen species; SD, standard deviation.
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f7-dddt-9-6191: ROS generation in treated MCF-7 cells.Notes: ROS generation as determined by DCFH-DA fluorescence intensity after 1.25, 2.5, 5, and 10 μg/mL of benzyltin compound C1 exposure at (A) 24 hours and (B) 48 hours. 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; DCFH-DA, 2′,7′-dichlorofluorescein diacetate; ROS, reactive oxygen species; SD, standard deviation.

Mentions: The normal cell metabolism of oxygen reduction to water leads to production of ROS molecules. Mitochondrial membrane disruption, apoptosis, and cell death have been proved to be related to oxidative stress due to generation of intracellular ROS. This alteration was assessed after 24 and 48 hours of treatment in MCF-7 cells using oxidation-sensitive fluorescent dye DCFH-DA. H2O2, which is a standard producer of ROS, was used as a positive control. As can be observed in Figure 7, there was a significant increasing trend in ROS production from negative control to positive control after treatment for both 24 and 48 hours. In addition, it is worth mentioning the higher twofold faster ROS generation at 24 hours with a 2.5 μg/mL concentration (IC50) in comparison to negative control, where ROS production was at a basal level. The significant increase of ROS generation after 48 hours at a lower concentration of compound C1 than IC50 (1.25 μg/mL) supports the high potential cytotoxicity of compound C1 through ROS burst, which suggests the stimulation of the mitochondrial-initiated events.


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)

ROS generation in treated MCF-7 cells.Notes: ROS generation as determined by DCFH-DA fluorescence intensity after 1.25, 2.5, 5, and 10 μg/mL of benzyltin compound C1 exposure at (A) 24 hours and (B) 48 hours. 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; DCFH-DA, 2′,7′-dichlorofluorescein diacetate; ROS, reactive oxygen species; SD, standard deviation.
© Copyright Policy
Related In: Results  -  Collection

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

f7-dddt-9-6191: ROS generation in treated MCF-7 cells.Notes: ROS generation as determined by DCFH-DA fluorescence intensity after 1.25, 2.5, 5, and 10 μg/mL of benzyltin compound C1 exposure at (A) 24 hours and (B) 48 hours. 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; DCFH-DA, 2′,7′-dichlorofluorescein diacetate; ROS, reactive oxygen species; SD, standard deviation.
Mentions: The normal cell metabolism of oxygen reduction to water leads to production of ROS molecules. Mitochondrial membrane disruption, apoptosis, and cell death have been proved to be related to oxidative stress due to generation of intracellular ROS. This alteration was assessed after 24 and 48 hours of treatment in MCF-7 cells using oxidation-sensitive fluorescent dye DCFH-DA. H2O2, which is a standard producer of ROS, was used as a positive control. As can be observed in Figure 7, there was a significant increasing trend in ROS production from negative control to positive control after treatment for both 24 and 48 hours. In addition, it is worth mentioning the higher twofold faster ROS generation at 24 hours with a 2.5 μg/mL concentration (IC50) in comparison to negative control, where ROS production was at a basal level. The significant increase of ROS generation after 48 hours at a lower concentration of compound C1 than IC50 (1.25 μg/mL) supports the high potential cytotoxicity of compound C1 through ROS burst, which suggests the stimulation of the mitochondrial-initiated events.

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