4-[(4-甲基苄基)氧]苯甲酸乙酯配合物体外和体内对癌细胞生长和凋亡的抑制作用

IF 2.6 4区 医学 Q3 CHEMISTRY, MEDICINAL
Abdul Auwal, Md Hasan Al Banna, Tasfik Ul Haque Pronoy, M Matakabbir Hossain, K M Rashel, Syed Rashel Kabir, Md Rezaul Haque Ansary, Farhadul Islam
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引用次数: 0

摘要

背景:癌症化疗是治疗癌症患者的最佳方法之一,因为它可以去除放射或手术无法去除的癌细胞。目的:我们的研究重点是确定具有轻微或无不良副作用的强效化疗药物。因此,本研究旨在合成一种大环芳香族化合物4-[(4-甲基苄基)氧]苯甲酸乙酯配合物,并检测其对人乳腺癌(MCF7)细胞的抗肿瘤活性。方法:采用体外和体内监测、细胞毒性、肿瘤重量、存活时间、肿瘤细胞生长抑制和血液学指标考察化合物的抗癌效果。采用定量逆转录酶聚合酶链反应(qRT-PCR)检测细胞生长和凋亡相关基因的表达。评估血液学和生化参数以检测小鼠宿主毒性。结果:该化合物对EAC和mcf7细胞均有明显的抗肿瘤活性。0.5 mg/kg和1.00 mg/kg剂量组细胞生长抑制率分别为40.70%和58.98% (p < 0.0001)。结果与临床使用的化疗药物顺铂相当(1.0 mg/kg体重剂量下,生长抑制率为59.2%)。高剂量(1.0 mg/kg/天)治疗组肿瘤重量(体积)比未治疗的eac小鼠减少4倍。1.00 mg/kg剂量组小鼠的平均生存时间较对照组延长83.07%以上(结论:该化合物具有良好的抗肿瘤活性,且对宿主无毒性或毒性很小)。因此,它有可能成为一种有效的化学制剂,然而,进一步的临床前和临床研究是必要的,使用动物和人类模型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
In vitro and In vivo Growth Inhibition and Apoptosis of Cancer Cells by Ethyl 4-[(4-methylbenzyl)oxy] Benzoate Complex.

Background: Cancer chemotherapy is one of the best ways to treat the patients with cancer as they can remove cancer cells, which can't be remove by radiation or surgery.

Aims: Our study is focused on identifying potent chemotherapeutic drugs with minor or no adverse side effects. Therefore, in this study, we aimed to synthesize ethyl 4-[(4-methylbenzyl)oxy] benzoate complex, a macrocyclic aromatic compound followed by testing its antineoplastic activity against Ehrlich ascites carcinoma (EAC) human breast cancer (MCF7) cells.

Methods: In vitro and in vivo assays were used for monitoring, cytotoxicity, tumor weight, survival time, tumor cell growth inhibition, and hematological parameters to investigate the anticancer effectiveness of the tested compound. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to examine the expression of growth and apoptotic related genes. Haematological and biochemical parameters were assessed to examine the host toxicity in mice.

Results: The compound exhibited notable anticancer activity against both EAC and MCF7cells. It showed 40.70 and 58.98 % cell growth inhibition at the doses of 0.5 and 1.00 mg/kg, respectively in comparison to that of control EAC-bearing mice (p < 0.0001). The result is comparable with clinically used chemotherapeutic drugs cisplatin (59.2% growth inhibition at the dose of 1.0 mg/kg body weight). A four folds reduction of tumor weight (volume) of treated group at higher dose (1.0 mg/kg/day) was noted in comparison to that of untreated EAC-bearing mice. Also, the mean survival time of treated mice (1.00 mg/kg) increased by more than 83.07% when compared to that of control EAC-bearing mice (p<0.001). In addition, EAC-bearing control mice showed drastic deterioration of RBC, WBC, and % of hemoglobin, however, in the treated mice these parameters were restored towards normal levels. A dose dependent reduction of growth and proliferation of MCF7 cells was noted in compound treated cells. Most importantly, apoptosis of MCF7 was induced followed by activation of pro-apoptotic genes (p53, Bax, Parp, Caspase-3, -8, -9) and inactivation of antiapoptotic, e.g. Bcl2 gene. Toxicological studies reveal that there were changes in hematological (RBC, WBC, % of Hb) and biochemical (serum glucose, cholesterol, creatinine, SGOT, SGPT) parameters during the treatment period, however, the parameters returned towards normal levels after the treatment period, indicating no or minor toxic effect of the compound on the host.

Conclusion: The compound has promising anticancer activity with no or minimum host toxic effects. Thus, it has the potential to be formulated as an effective chemo-agent, however, further preclinical and clinical research is imperative using animal and human models.

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来源期刊
Anti-cancer agents in medicinal chemistry
Anti-cancer agents in medicinal chemistry ONCOLOGY-CHEMISTRY, MEDICINAL
CiteScore
5.10
自引率
3.60%
发文量
323
审稿时长
4-8 weeks
期刊介绍: Formerly: Current Medicinal Chemistry - Anti-Cancer Agents. Anti-Cancer Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of anti-cancer agents. Each issue contains a series of timely in-depth reviews and guest edited issues written by leaders in the field covering a range of current topics in cancer medicinal chemistry. The journal only considers high quality research papers for publication. Anti-Cancer Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in cancer drug discovery.
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