Background: Breast cancer is a type of cancer that affects more women throughout the world, in developing anddeveloped countries. 2-AEH2P is a phospholipid analog of cellular membrane, which makes it different from ex...Background: Breast cancer is a type of cancer that affects more women throughout the world, in developing anddeveloped countries. 2-AEH2P is a phospholipid analog of cellular membrane, which makes it different from existing molecules fortheir absorption, stability and display anti-inflammatory, anti-proliferative and pro-apoptotic properties. Methods: MCF-7 humanbreast adenocarcinoma cells were treated with 2-AEH2P. The viability and adhesion cells were evaluated by MTT assay. Cell cyclephases, apoptosis, markers and mitochondrial potential were assessed by flow cytometry. Morphological ultrastructural analyzeswere performed by laser confocal microscopy. Results: MCF-7 Tumor cells acquired round shapes, lost cytoplasmic expansions,formed clusters in suspension and decreased significantly viability. There were changes in the morphology, membrane fragmentationand loss of cytoplasmic projection. The obtained concentrations for IC50% were 37.2;25.8;1.8 mM for periods of 24, 48 and 72 h,respectively. Changes in the distribution of cell population phases of the cell cycle showed an increase in fragmented DNA and anincrease in the G2/M phase. The expression β-gal showed proliferative reduction induced by 2-AEH2P. Laser confocal microscopyshowed changes in the mitochondrial membrane and alteration in distribution. Proliferative index of MCF-7 tumor cells treated with2-AEH2P decreased significantly when compared to fibroblast normal cells. The compound 2-AEH2P is a phospholipid withantiproliferative potential and apoptosis modulator.展开更多
A new series of 3-(methylthio)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine derivatives was synthesized. The structures of the new derivatives were confirmed by the spectral data and elemental analyses. The antitumor activit...A new series of 3-(methylthio)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine derivatives was synthesized. The structures of the new derivatives were confirmed by the spectral data and elemental analyses. The antitumor activity of this series against human breast adenocarcinoma cell line MCF7 was evaluated. Out of twenty new derivatives, ten were revealed mild to moderate activity compared with doxorubicin as a reference antitumor. Among this new series N-(2-chlorophenyl)-2-(3-(methylthio)-4-oxo-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-5(4H)-yl)acetamide (13a) was found the most active one with IC50 equal to 23 μM.展开更多
The aim of the present in vitro study was to assess the tumoricidal potential of the following natural peptides belonging to the Cecropin family, namely Cecropin A and B, on a series of tumour cell lines: MDA-MB-231 (...The aim of the present in vitro study was to assess the tumoricidal potential of the following natural peptides belonging to the Cecropin family, namely Cecropin A and B, on a series of tumour cell lines: MDA-MB-231 (breast adenocarcinoma) and M14K (human mesothelioma). The experimental results reveal that the cytotoxic effects of the two peptides depend on their concentration. Their efficiency is significant at 120 μM concentrations and it persists even at 60 μM concentrations. The effects were insignificant at 30 μM concentrations. On the other hand, the cytotoxic potential was not significantly dependant on the type of peptide but more on the type of tumour cell line used. The MDA MB 231 line cells were much more sensitive to the action of Cecropins A and B than the M14K line cells. The prospects brought about by this experimental research consist of the collection of in vitro experimental data on the tumoricidal potential of these natural cytotoxic peptides on tumour cells. This will enable specialists to develop future in vivo experimental models in order to test the antitumor effect of these cytotoxic peptides. The ultimate goal would be the discovery of agents with efficient antitumor properties, i.e. with maximum tumoricidal effects and minimum toxic side effects.展开更多
Aim:Cancer stem cells(CSCs)are highly resistant to chemotherapy andγ-irradiation.Neutrons have a high linear energy transfer,which can lead to extensive damage to the DNA of tumor cells and CSCs.The aim of this work ...Aim:Cancer stem cells(CSCs)are highly resistant to chemotherapy andγ-irradiation.Neutrons have a high linear energy transfer,which can lead to extensive damage to the DNA of tumor cells and CSCs.The aim of this work was to compare the sensitivity of MCF-7 human breast adenocarcinoma cells and CSCs toγ-andγ,n-irradiation.Methods:To increase the number of CSCs,MCF-7 cells were cultured as mammospheres.γ-irradiation was carried out in a GUT-200M device(^(60)Co source)in the dose range of 1-8 Gy at a dose rate of 0.75 Gy/min.γ,n-irradiation was carried out in an IR-8 reactor in the dose range of 0.05-2 Gy at a dose rate of 0.06 Gy/min.DNA DSB formation was assessed by the level ofγH2AX foci using fluorescence microscopy and flow cytometry.CSCs were identified by flow cytometry as CD44^(+)/CD24^(-/low) cells.Results:We showed thatγ,n-irradiation induced the formation ofγH2AX foci of a larger size than didγ-irradiation and led to more severe DNA damage per 1 Gy.Moreover,γ,n-radiation was found to have a high relative biological effectiveness(RBE)as assessed by the cell survival rate,the number of CSCs in culture,and the ability of CSCs to repopulate.The highest RBE of neutron radiation was observed at low doses,when cell survival rate decreased by only 5%-10%.With an increase in the radiation dose,the RBE value decreased for all studied parameters,but it remained as high as 5.Conclusion:γ,n-radiation is highly effective against CSCs.Our results explain the efficacy of neutron therapy for resistant forms of breast cancer.展开更多
Two genes from grapevine coding for resvera-trol synthase, named RS1 and RS2, were cloned by RT-PCR. An Escherichia coli expression vector was constructed by insertion of RS1 into pBV221. A specific protein with the s...Two genes from grapevine coding for resvera-trol synthase, named RS1 and RS2, were cloned by RT-PCR. An Escherichia coli expression vector was constructed by insertion of RS1 into pBV221. A specific protein with the same molecular weight (42 ku) as the resveratrol synthase was expressed and used to prepare the rabbit antiserum. A plant expression vector was constructed by inserting the RS1 gene into pBin438 downstream of the doubled CaMV 35S promoter and TMV-Ω fragment. PCR-positive transgenic tobacco plants were obtained after transformation with Agrobacterium tumefaclens LBA4404 harboring the plant expression vector. Southern blot analysis demonstrated that the foreign gene was integrated into the tobacco genome. The results of RT-PCR and Western blot indicated that the RS1 gene was transcribed and expressed. Formation of resveratrol in transgenic tobacco was further determined by thin-layer chromatography of silica gel and HPLC. Increased accumulation of human breast adenocarcinoma cells in G0 and展开更多
基金Fundação de Amparo a Pesquisa do Estado de São Paulo–FAPESP(Process number 2014/02344-1)Conselho Nacional de Desenvolvimento Científico e Tecnológico–CNPq(Process number 305056/2019-0).
文摘Background: Breast cancer is a type of cancer that affects more women throughout the world, in developing anddeveloped countries. 2-AEH2P is a phospholipid analog of cellular membrane, which makes it different from existing molecules fortheir absorption, stability and display anti-inflammatory, anti-proliferative and pro-apoptotic properties. Methods: MCF-7 humanbreast adenocarcinoma cells were treated with 2-AEH2P. The viability and adhesion cells were evaluated by MTT assay. Cell cyclephases, apoptosis, markers and mitochondrial potential were assessed by flow cytometry. Morphological ultrastructural analyzeswere performed by laser confocal microscopy. Results: MCF-7 Tumor cells acquired round shapes, lost cytoplasmic expansions,formed clusters in suspension and decreased significantly viability. There were changes in the morphology, membrane fragmentationand loss of cytoplasmic projection. The obtained concentrations for IC50% were 37.2;25.8;1.8 mM for periods of 24, 48 and 72 h,respectively. Changes in the distribution of cell population phases of the cell cycle showed an increase in fragmented DNA and anincrease in the G2/M phase. The expression β-gal showed proliferative reduction induced by 2-AEH2P. Laser confocal microscopyshowed changes in the mitochondrial membrane and alteration in distribution. Proliferative index of MCF-7 tumor cells treated with2-AEH2P decreased significantly when compared to fibroblast normal cells. The compound 2-AEH2P is a phospholipid withantiproliferative potential and apoptosis modulator.
文摘A new series of 3-(methylthio)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine derivatives was synthesized. The structures of the new derivatives were confirmed by the spectral data and elemental analyses. The antitumor activity of this series against human breast adenocarcinoma cell line MCF7 was evaluated. Out of twenty new derivatives, ten were revealed mild to moderate activity compared with doxorubicin as a reference antitumor. Among this new series N-(2-chlorophenyl)-2-(3-(methylthio)-4-oxo-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-5(4H)-yl)acetamide (13a) was found the most active one with IC50 equal to 23 μM.
文摘The aim of the present in vitro study was to assess the tumoricidal potential of the following natural peptides belonging to the Cecropin family, namely Cecropin A and B, on a series of tumour cell lines: MDA-MB-231 (breast adenocarcinoma) and M14K (human mesothelioma). The experimental results reveal that the cytotoxic effects of the two peptides depend on their concentration. Their efficiency is significant at 120 μM concentrations and it persists even at 60 μM concentrations. The effects were insignificant at 30 μM concentrations. On the other hand, the cytotoxic potential was not significantly dependant on the type of peptide but more on the type of tumour cell line used. The MDA MB 231 line cells were much more sensitive to the action of Cecropins A and B than the M14K line cells. The prospects brought about by this experimental research consist of the collection of in vitro experimental data on the tumoricidal potential of these natural cytotoxic peptides on tumour cells. This will enable specialists to develop future in vivo experimental models in order to test the antitumor effect of these cytotoxic peptides. The ultimate goal would be the discovery of agents with efficient antitumor properties, i.e. with maximum tumoricidal effects and minimum toxic side effects.
基金The work was supported by the National Research Center“Kurchatov Institute”.
文摘Aim:Cancer stem cells(CSCs)are highly resistant to chemotherapy andγ-irradiation.Neutrons have a high linear energy transfer,which can lead to extensive damage to the DNA of tumor cells and CSCs.The aim of this work was to compare the sensitivity of MCF-7 human breast adenocarcinoma cells and CSCs toγ-andγ,n-irradiation.Methods:To increase the number of CSCs,MCF-7 cells were cultured as mammospheres.γ-irradiation was carried out in a GUT-200M device(^(60)Co source)in the dose range of 1-8 Gy at a dose rate of 0.75 Gy/min.γ,n-irradiation was carried out in an IR-8 reactor in the dose range of 0.05-2 Gy at a dose rate of 0.06 Gy/min.DNA DSB formation was assessed by the level ofγH2AX foci using fluorescence microscopy and flow cytometry.CSCs were identified by flow cytometry as CD44^(+)/CD24^(-/low) cells.Results:We showed thatγ,n-irradiation induced the formation ofγH2AX foci of a larger size than didγ-irradiation and led to more severe DNA damage per 1 Gy.Moreover,γ,n-radiation was found to have a high relative biological effectiveness(RBE)as assessed by the cell survival rate,the number of CSCs in culture,and the ability of CSCs to repopulate.The highest RBE of neutron radiation was observed at low doses,when cell survival rate decreased by only 5%-10%.With an increase in the radiation dose,the RBE value decreased for all studied parameters,but it remained as high as 5.Conclusion:γ,n-radiation is highly effective against CSCs.Our results explain the efficacy of neutron therapy for resistant forms of breast cancer.
基金This work was supported by the National Natural Science Foundation of China (Grant No. 39570464).
文摘Two genes from grapevine coding for resvera-trol synthase, named RS1 and RS2, were cloned by RT-PCR. An Escherichia coli expression vector was constructed by insertion of RS1 into pBV221. A specific protein with the same molecular weight (42 ku) as the resveratrol synthase was expressed and used to prepare the rabbit antiserum. A plant expression vector was constructed by inserting the RS1 gene into pBin438 downstream of the doubled CaMV 35S promoter and TMV-Ω fragment. PCR-positive transgenic tobacco plants were obtained after transformation with Agrobacterium tumefaclens LBA4404 harboring the plant expression vector. Southern blot analysis demonstrated that the foreign gene was integrated into the tobacco genome. The results of RT-PCR and Western blot indicated that the RS1 gene was transcribed and expressed. Formation of resveratrol in transgenic tobacco was further determined by thin-layer chromatography of silica gel and HPLC. Increased accumulation of human breast adenocarcinoma cells in G0 and
