研究两种新型4-MMPB类似物作为有效的脂氧合酶抑制剂在前列腺癌治疗中的作用。

IF 1.9 3区 生物学 Q2 BIOLOGY
Sonia Iranpour, Aseel Kamil Mohammed Al-Mosawi, Ahmad Reza Bahrami, Hamid Sadeghian, Maryam M Matin
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引用次数: 5

摘要

背景:脂氧合酶是治疗前列腺癌的重要信号介质之一。本研究提出,4-甲基-2-(4-甲基哌嗪基)嘧啶[4,5-b]苯并噻嗪(4- mmpb)及其两个类似物4-丙基-2-(4-甲基哌嗪基)嘧啶[4,5-b]苯并噻嗪(4- pmpb)和4-乙基-2-(4-甲基哌嗪基)嘧啶[4,5-b]苯并噻嗪(4- empb)在前列腺癌中具有抗肿瘤特性。方法:合成化合物后,采用3-[4,5-二甲基噻唑-2-酰基]-2,5-二苯基溴化四唑(MTT)法研究4- mmpb及其两种类似物对PC-3癌细胞和HDF正常细胞的细胞毒作用,并用流式细胞术分析细胞死亡机制。最后,在免疫功能低下的C57BL/6小鼠模型上研究了上述化合物的抗肿瘤作用。结果:4-PMPB和4-EMPB对PC-3细胞的抗癌作用与4-MMPB相似,而对正常细胞无作用。细胞凋亡和铁下垂是诱导这些癌细胞死亡的主要机制。此外,体内实验结果表明,这两种类似物具有与4-MMPB相似的抗癌作用,导致肿瘤生长延迟,在减肥和组织学调查中没有任何明显的副作用。结论:因此,我们的研究结果表明,通过4-MMPB类似物特异性靶向脂氧合酶可以被认为是PC治疗的一种治疗选择,尽管这需要进一步的研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Investigating the effects of two novel 4-MMPB analogs as potent lipoxygenase inhibitors for prostate cancer treatment.

Investigating the effects of two novel 4-MMPB analogs as potent lipoxygenase inhibitors for prostate cancer treatment.

Investigating the effects of two novel 4-MMPB analogs as potent lipoxygenase inhibitors for prostate cancer treatment.

Investigating the effects of two novel 4-MMPB analogs as potent lipoxygenase inhibitors for prostate cancer treatment.

Background: Lipoxygenases are one of the critical signaling mediators which can be targeted for human prostate cancer (PC) therapy. In this study, 4-methyl-2-(4-methylpiperazinyl)pyrimido[4,5-b]benzothiazine (4-MMPB) and its two analogs, 4-propyl-2-(4-methylpiperazinyl)pyrimido[4,5-b]benzothiazine (4-PMPB) and 4-ethyl-2-(4-methylpiperazinyl)pyrimido[4,5-b]benzothiazine (4-EMPB), were proposed to have anti-tumor properties in prostate cancer.

Methods: After synthesizing the compounds, cytotoxic effects of 4-MMPB and its two analogs against PC-3 cancerous and HDF normal cells were investigated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and then mechanism of cell death was assessed by flow cytometry. Finally, the anti-tumor effects of the mentioned compounds were investigated in an immunocompromised C57BL/6 mouse model.

Results: 4-PMPB and 4-EMPB had similar anti-cancer effects on PC-3 cells as compared with 4-MMPB, while they were not effective on normal cells. Moreover, apoptosis and ferroptosis were the main mechanisms of induced cell death in these cancerous cells. Furthermore, in vivo results indicated that both analogs had similar anti-cancer effects as 4-MMPB, leading to delayed tumor growth without any noticeable side effects in weight loss and histological investigations.

Conclusion: Thus, our results suggest that specific targeting of lipoxygenases via 4-MMPB analogs can be considered as a treatment of choice for PC therapy, although it requires further investigations.

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来源期刊
CiteScore
5.20
自引率
0.00%
发文量
0
审稿时长
>12 weeks
期刊介绍: Journal of Biological Research-Thessaloniki is a peer-reviewed, open access, international journal that publishes articles providing novel insights into the major fields of biology. Topics covered in Journal of Biological Research-Thessaloniki include, but are not limited to: molecular biology, cytology, genetics, evolutionary biology, morphology, development and differentiation, taxonomy, bioinformatics, physiology, marine biology, behaviour, ecology and conservation.
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