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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

AO/PI staining of untreated MCF-7 cells and MCF-7 cells treated with IC50 of compound C1 for 24 and 48 hours.Notes: (A and B) Treated cells after 24 and 48 hours, respectively. (C) Untreated cells. (D) Percentages of viable, early apoptotic, late apoptotic, and necrotic cells. *Demonstrates significant difference (P<0.05) compared with control.Abbreviations: AO, acridine orange; C1, compound 1 [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride; EA, early apoptotic cells; h, hours; IC50, half maximal inhibitory concentration; LA, late apoptotic cells; N, necrotic cells; PI, propidium iodide; VI, viable cells.
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f6-dddt-9-6191: AO/PI staining of untreated MCF-7 cells and MCF-7 cells treated with IC50 of compound C1 for 24 and 48 hours.Notes: (A and B) Treated cells after 24 and 48 hours, respectively. (C) Untreated cells. (D) Percentages of viable, early apoptotic, late apoptotic, and necrotic cells. *Demonstrates significant difference (P<0.05) compared with control.Abbreviations: AO, acridine orange; C1, compound 1 [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride; EA, early apoptotic cells; h, hours; IC50, half maximal inhibitory concentration; LA, late apoptotic cells; N, necrotic cells; PI, propidium iodide; VI, viable cells.

Mentions: The morphological changes that relate to apoptosis and cell death induced by compound C1 were analyzed employing AO/PI fluorescence microscopy double staining after treatment for 24 and 48 hours. Figure 6A and B show the morphological features of different stages of cell death after 24 and 48 hours’ treatment, respectively. The untreated cells were observed with a green, normal, and large nuclear structure and were AO (+) and PI (−) (Figure 6C). When AO and PI, interpolating nucleic acid dyes, bind to DNA, they release green and orange fluorescence, respectively. Viable cells and cells at an early stage of apoptosis stain with AO, while cells at a late stage of apoptosis and necrotic cells stain with both AO and PI. Early apoptotic cells with a green condensed nuclear structure (AO [+] and PI [−]); cells at a late stage of apoptosis with a condensed nuclear structure and reddish-orange color (AO [+] and PI [+]); and necrotic red, swollen, enlarged cells with nuclei (AO [+] and PI [+]) are shown in Figure 6A and B. The percentages of viable, early apoptotic, late apoptotic, and necrotic cells were quantified in more than 200 treated MCF-7 cells. As shown in Figure 6D, the percentage of late apoptotic cells was increased significantly after exposure of cells to agent C1 for 24 and 48 hours, while increase in the percentage of early apoptotic cells was significant only in cells treated for 24 hours.


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)

AO/PI staining of untreated MCF-7 cells and MCF-7 cells treated with IC50 of compound C1 for 24 and 48 hours.Notes: (A and B) Treated cells after 24 and 48 hours, respectively. (C) Untreated cells. (D) Percentages of viable, early apoptotic, late apoptotic, and necrotic cells. *Demonstrates significant difference (P<0.05) compared with control.Abbreviations: AO, acridine orange; C1, compound 1 [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride; EA, early apoptotic cells; h, hours; IC50, half maximal inhibitory concentration; LA, late apoptotic cells; N, necrotic cells; PI, propidium iodide; VI, viable cells.
© Copyright Policy
Related In: Results  -  Collection

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

f6-dddt-9-6191: AO/PI staining of untreated MCF-7 cells and MCF-7 cells treated with IC50 of compound C1 for 24 and 48 hours.Notes: (A and B) Treated cells after 24 and 48 hours, respectively. (C) Untreated cells. (D) Percentages of viable, early apoptotic, late apoptotic, and necrotic cells. *Demonstrates significant difference (P<0.05) compared with control.Abbreviations: AO, acridine orange; C1, compound 1 [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride; EA, early apoptotic cells; h, hours; IC50, half maximal inhibitory concentration; LA, late apoptotic cells; N, necrotic cells; PI, propidium iodide; VI, viable cells.
Mentions: The morphological changes that relate to apoptosis and cell death induced by compound C1 were analyzed employing AO/PI fluorescence microscopy double staining after treatment for 24 and 48 hours. Figure 6A and B show the morphological features of different stages of cell death after 24 and 48 hours’ treatment, respectively. The untreated cells were observed with a green, normal, and large nuclear structure and were AO (+) and PI (−) (Figure 6C). When AO and PI, interpolating nucleic acid dyes, bind to DNA, they release green and orange fluorescence, respectively. Viable cells and cells at an early stage of apoptosis stain with AO, while cells at a late stage of apoptosis and necrotic cells stain with both AO and PI. Early apoptotic cells with a green condensed nuclear structure (AO [+] and PI [−]); cells at a late stage of apoptosis with a condensed nuclear structure and reddish-orange color (AO [+] and PI [+]); and necrotic red, swollen, enlarged cells with nuclei (AO [+] and PI [+]) are shown in Figure 6A and B. The percentages of viable, early apoptotic, late apoptotic, and necrotic cells were quantified in more than 200 treated MCF-7 cells. As shown in Figure 6D, the percentage of late apoptotic cells was increased significantly after exposure of cells to agent C1 for 24 and 48 hours, while increase in the percentage of early apoptotic cells was significant only in cells treated for 24 hours.

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