Cytotoxicity and apoptosis induced by a plumbagin derivative in estrogen positive MCF-7 breast cancer cells.
Cytotoxicity and apoptosis induced by a plumbagin derivative in estrogen positive MCF-7 breast cancer cells.
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DOI：
10.2174/18715206113136660369
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发表时间：
2014-01
影响因子：
2.8
通讯作者：
Kaur M
中科院分区：
文献类型：
--
作者：
Sagar S;Esau L;Moosa B;Khashab NM;Bajic VB;Kaur M
白花丹[5-羟基-2-甲基-1，4-萘醌]是一种著名的植物来源的抗癌先导化合物。为了提高它的抗癌潜力，人们已经进行了一些努力来合成它的类似物和衍生物。在这项研究中，白花丹及其五个衍生物在一个正常细胞系和四个人类癌细胞系中进行了抗增殖能力的评估。用衍生物处理后，各种癌细胞株的生长受到剂量和时间依赖性的抑制。化合物的预筛选使我们将进一步的研究重点放在乙酰白花青素上，它对正常的BJ细胞和HepG2细胞的毒性都非常低。通过APO-Percentage染色、caspase-3/7活化、活性氧产生和细胞周期分析，确定诱导细胞凋亡的机制。实时定量聚合酶链式反应检测细胞凋亡相关基因(P53、MDM2、NF-kB、Bad、Bax、Bcl2、Casp-7)的表达。APO Percentage染色阳性，caspase-3/7活性增强，ROS生成增加，促凋亡基因表达增强，提示乙酰白花素通过诱导细胞凋亡而对MCF-7细胞具有抗肿瘤作用。这项研究的一个关键亮点是乙酰白藜芦素对正常BJ细胞的低毒性和可忽略的肝脏毒性(基于HepG2细胞株的数据)。总体而言，结果表明，毒性降低的乙酰白花黄素有可能成为一种新的铅分子，用于检测雌激素阳性乳腺癌。
Plumbagin [5-hydroxy- 2-methyl-1, 4-naphthaquinone] is a well-known plant derived anticancer lead compound. Several efforts have been made to synthesize its analogs and derivatives in order to increase its anticancer potential. In the present study, plumbagin and its five derivatives have been evaluated for their antiproliferative potential in one normal and four human cancer cell lines. Treatment with derivatives resulted in dose- and time-dependent inhibition of growth of various cancer cell lines. Prescreening of compounds led us to focus our further investigations on acetyl plumbagin, which showed remarkably low toxicity towards normal BJ cells and HepG2 cells. The mechanisms of apoptosis induction were determined by APOPercentage staining, caspase-3/7 activation, reactive oxygen species production and cell cycle analysis. The modulation of apoptotic genes (p53, Mdm2, NF-kB, Bad, Bax, Bcl-2 and Casp-7) was also measured using real time PCR. The positive staining using APOPercentage dye, increased caspase-3/7 activity, increased ROS production and enhanced mRNA expression of proapoptotic genes suggested that acetyl plumbagin exhibits anticancer effects on MCF-7 cells through its apoptosis-inducing property. A key highlighting point of the study is low toxicity of acetyl plumbagin towards normal BJ cells and negligible hepatotoxicity (data based on HepG2 cell line). Overall results showed that acetyl plumbagin with reduced toxicity might have the potential to be a new lead molecule for testing against estrogen positive breast cancer.
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影响因子：
4.8
作者：
Belmokhtar, CA;Hillion, J;Ségal-Bendirdjian, E
通讯作者：
Ségal-Bendirdjian, E
影响因子：
4
作者：
Ahmad, Aamir;Banerjee, Sanjeev;Sarkar, Fazlul H.
通讯作者：
Sarkar, Fazlul H.
影响因子：
11.2
作者：
Aziz, Moammir H.;Dreckschmidt, Nancy E.;Verma, Ajit K.
通讯作者：
Verma, Ajit K.
影响因子：
5.7
作者：
Huang, LL;Pardee, AB
通讯作者：
Pardee, AB
影响因子：
11.5
作者：
Buchholz, TA;Garg, AK;Sahin, AA
通讯作者：
Sahin, AA