Biochemistry and Biophysical Laboratory, Butantan Institute, Sao Paulo, Brazil.
Anticancer Res. 2012 Jan;32(1):95-104.
Antineoplastic phospholipids (ALPs) represent a promising class of drugs with a novel mode of action undergoes rapid turnover in the cell membrane of tumors, interfering with lipid signal transduction, inducing cell death. The aim of this study was to investigate the synthetic phosphoethanolamine (Pho-s) as a new anticancer agent.
Cell viability and morphology were assessed by (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Hoechst and rhodamine staining. Apoptosis was assessed by Annexin V and propidium iodide (PI) staining, caspase-3 activity, mitochondrial membrane potential (ΔmΨ) and cell cycle analysis, combined with evaluation of tumor growth in Ehrlich Ascites Tumor (EAT) bearing mice.
We found that Pho-s 2.30 mg/ml induced cytotoxicity in all tumor cell lines studied without affecting normal cells. In vitro studies with EAT cells indicated that Pho-s induced apoptosis, demonstrated by an increase in Annexin-V positive cells, loss of mitochondrial potential (ΔmΨ) and increased caspase-3 activity. It was also shown to increase the sub-G(1) apoptotic fraction and inhibit progression to the S phase of the cell cycle. Additionally, antitumor effects on the EAT-bearing mice showed that Pho-s, at a concentration of 35 and 70 mg/kg, inhibited tumor growth and increased the lifespan of animals without causing liver toxicity.
These findings suggest that Pho-s is a potential anticancer candidate drug.
抗肿瘤磷脂（ALPs）代表了一类有前途的药物，具有一种新型的作用模式，在肿瘤细胞膜中快速转化，干扰脂质信号转导，诱导细胞死亡。本研究旨在研究合成的磷酸乙醇胺（Pho-s）作为一种新的抗癌剂。
通过（3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物（MTT）、Hoechst 和罗丹明染色评估细胞活力和形态。通过 Annexin V 和碘化丙啶（PI）染色、caspase-3 活性、线粒体膜电位（ΔmΨ）和细胞周期分析评估细胞凋亡，结合荷 Ehrlich 腹水瘤（EAT）小鼠的肿瘤生长评估。
我们发现 Pho-s 2.30 mg/ml 在研究的所有肿瘤细胞系中均诱导细胞毒性，而不影响正常细胞。用 EAT 细胞进行的体外研究表明，Pho-s 诱导细胞凋亡，通过增加 Annexin-V 阳性细胞、线粒体电位（ΔmΨ）丧失和 caspase-3 活性增加来证明。它还显示增加亚 G(1)凋亡部分并抑制细胞周期进入 S 期。此外，对荷 EAT 小鼠的抗肿瘤作用表明，Pho-s 在 35 和 70 mg/kg 的浓度下抑制肿瘤生长并延长动物的寿命，而不会引起肝毒性。
这些发现表明 Pho-s 是一种有潜力的抗癌候选药物。
