Pyrazole Derivatives Induce Apoptosis via ROS Generation in the Triple Negative Breast Cancer Cells, MDA-MB-468
Maryam AshourpourFatemeh Mostafavi HosseiniMohsen AminiEbrahim Saeedian MoghadamFaranak KazerouniSeyed Yousef ArmanZahra Shahsavari
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Triple-negative breast cancer accounts for approximately 15-20% of all breast carcinomas and is associated with earlier age of onset, aggressive clinical course, and dismal prognosis. A series of 1,3-diaryl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1 H-Pyrazole and 1,3-diaryl-5- (3,4,5-trimethoxyphenyl)- 1 H-Pyrazole were evaluated for their anticancer activity against MDA-MB-468, human triple negative breast cancer cell line.The cytotoxic effects of Pyrazole derivatives on the growth of MDA-MB-468 and AGO1522 were determined using MTT assay. Annexin-V-FITC and PI staining were performed to detect apoptosis and cell cycle distribution using Flow cytometry. The level of Reactive oxygen species (ROS) formation and caspase 3 activity were determined accordingly.Pyrazole derivatives induced a dose and time-dependent cell toxicity in MDA-MB-468 compared with untreated cells. The results showed that 3-(4-methoxyphenyl)-1-(p-tolyl)-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-Pyrazole (3f) was the most active compound with IC50 values 14.97 μM and 6.45 μM compared with Paclitaxel with IC50 values 49.90 μM and 25.19 μM, after 24 and 48 hours, respectively. Upon treatment with 14.97 μM of 3f after 24 h, the compound induced cell cycle arrest in S phase. 3f provoked apoptosis was accompanied by the elevated level of ROS and increased caspase 3 activity in MDA-MB-468 cells compared with untreated cells.The overall results of the present study provided evidence for the cytotoxicity of compound 3f against MDA-MB-468 cells in comparison to reference standard, Paclitaxel. It proves that compound 3f can trigger apoptosis through ROS production and caspase 3 activation. These bring supportive data for future investigations that will lead to their use in cancer therapy. .
Keywords:
Pyrazole
MTT assay
Triple-negative breast cancer
MCF-7
MCF-7
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MCF-7
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To observe the effect of NL-608 (a nutlin analog) on apoptosis induction in human breast cancer MCF-7 cells in vitro, and investigate the relevant molecular mechanism.The effect of NL-608 on proliferation of MCF-7 cells was determined by MTT assay. The apoptosis in MCF-7 cells was determined by flow cytometry with annexin V-FITC and PI. The activity of caspase 3, caspase 8 and caspase 9 was determined with caspase activity assay kit and Western blot, and the proteins of Fas and FasL were determined by Western blot.NL-608 showed a dose-dependent inhibitory effect on the proliferation of MCF-7 cells. It induced apoptosis in MCF-7 cells in a dose-dependent manner. The activity of caspase 3 and caspase 8 in MCF-7 cells was increased with the increasing concentration of NL-608, but caspase 9 had no changes. The proteins of Fas and FasL were increased in a dose-dependent manner.NL-608 induces apoptosis in MCF-7 cells in vitro through inducing caspase 3 activity and death receptor-mediated signal pathway.
MCF-7
Fas ligand
MTT assay
Caspase 8
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MCF-7
Cancer cell lines
Expression (computer science)
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Objective To investigate the application of flow cytometry in the assessment of anti-tumor drugs chemosensitivity.[WT5”HZ]Methods Sub-G_1 and Annexin V assays were used to detect the apoptosis of Molt-4 cell line and fresh gastrointestinal cancer cells which were exposed to anti-tumor drugs,such as 5-fluorouracil and Paclitaxel.The outcomes were compared with the ones from MTT colormetric assay.Results[WT5”BZ] The outcome of Annexin V assay or Sub-G_1 assay was closely associated with MTT assay.But the time point of the maximum cytotoxicity of drugs detected by Annexin V assay was earlier than that by MTT assay or by Sub-G_1 assay.Conclusion Annexin V and Sub-G_1 assays could be used as the effective method to test the anti-tumro drugs chemosensitivity.Annexin V assay would be a sensitive,rapid,reliable approach for measuring anti-tumor drugs chemosensitivity.
MTT assay
Chemosensitivity assay
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To enhance the penetration of P53 into tumor cells by fusion it with the cell penetrating peptide 9R. The fusion gene of 9R-p53 was cloned into the expression vector. The fusion protein, CPPs-P53, was expressed and purified. We detected the rate of cell growth inhibition and apoptosis by MTT and Annexin-V-FITC/PI double stained method respectively for measuring its effect on tumor cells. CPPs-P53 and P53 were successfully expressed and purified, the purity of both proteins reached up to 90%. MTT assay showed that the cell growth inhibition by CPPs-P53 was more efficient than P53, and the rate of cell growth inhibition is dose-dependent. The apoptosis experiment showed that P53 could induce apoptosis of tumor cells. Compared with the P53, CPPs-P53 had a more significant effect in inducing cell apoptosis (**P < 0.01). The CPPs-P53 shows more significant effects than P53 in inhibiting cell growth and inducing apoptosis on tumor cells.
MTT assay
P53 protein
Growth inhibition
Cell-penetrating peptide
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A series of cyano (ligand) cobaloximes have been prepared where, the ligand is pyrazole (Pz), 1-(acetamido)pyrazole (Apz), 1-(N-methylacetamido)pyrazole (MAPz), l-(acetamido)-3,5-dimethylpyrazole (MADMPz). The complex K[(CN)Co(D 2 H 2 )SCN] reacts with ethanolic solution of pyrazole or pyrazole amido ligands to form mixed ligand complexes. In all these complexes, the pyrazoles act as monodentate ligands and bind to Co I I I through N-2 of pyrazole ring.
Pyrazole
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调查在临床的应用由流动血细胞计数反肿瘤药测试以便为一篇小说的建立提供试验性、理论的基础的 chemosensitivity 的可行性的目的反肿瘤药敏感测试并且屏蔽特别的反肿瘤药。方法检测 Molt-4 的 12 个案例的 apoptosis 率房间线，由 Sub-G1 和在在不同时间和结果的反肿瘤药的效果下面的流动血细胞计数的 Annexin V 试金的新鲜临床的胃肠的肿瘤房间的 57 个案例与一 MTT (3-( 4,5-dimethylthiazolyl-2 ) -2,5-diphenyltetrazolium 溴化物)相比是试金。结果 Molt-4 房间上的药的致命性，临床的胃肠的肿瘤房间由采用 Annexin V， Sub-G1 和 MTT 与反药的代理时间有积极关联试金。Annexin V 试金的招致药的最大的致命性比 MTT 比色测定高， Sub-G1 的比 MTT 试金， Annexin V 的虚拟时间和 Sub-G1 试金显然比 MTT 的早低比色测定。结论 Annexin V 和流动血细胞计数的 Sub-G1 试金能作为测试反肿瘤药 chemosensitivity 的有势力协议被拿。Annexin V 试金被更多展示敏感，简明，与 MTT 比色测定和它的严峻的试金拥有的古典 chemosensitivity 相比可靠临床的应用价值。
MTT assay
Annexin A5
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