(R)-Edelfosine is a synthetic lipid agent belonging to a class of compounds with antitumor and antiparasitic activities[1]. (R)-Edelfosine can induce apoptosis-like cell death in tumor cells by targeting FOF1-ATP synthase on mitochondria and lipid rafts[2]. (R)-Edelfosine also exhibits antileishmanial and antischistosomal activities[3]. (R)-Edelfosine acts as a novel HIV-1 latency-reversing agent[4].
In vitro, treatment of prostate cancer cells (LNCaP, PC3, and DU145) with (R)-Edelfosine (5–30μM) for 24–72 hours leads to accumulation in the endoplasmic reticulum, inducing endoplasmic reticulum stress, significantly promoting caspase-3 activation and PARP cleavage, and triggering apoptosis[5]. Treatment of non-small cell lung cancer cells (NCI-H157, NCI-H520, NCI-H522) with (R)-Edelfosine (2.6–100μM) for 24–72 hours inhibits phospholipase C-B1 activity, induces G2/M phase arrest and c-Jun N-terminal kinase activation, and significantly promotes apoptosis and necrosis[6].
In vivo, daily oral administration of (R)-Edelfosine (30mg/kg) starting from day 5 after tail vein injection of 435-Lung-eGFP-CMV/Luc metastatic cancer cells until week 12 in nude mice significantly inhibits metastatic tumor colonization in the lungs and brain, while prolonging the survival of tumor-bearing mice[7]. Oral administration of (R)-Edelfosine (5–20mg/kg) three times per week in an orthotopic LNCaP cell xenograft mouse model, combined with androgen deprivation (bilateral orchiectomy), significantly suppresses tumor volume growth[8].
References:
[1] Teixeira SF, Rodrigues CP, Costa CJS, et al. Edelfosine: An Antitumor Drug Prototype. Anticancer Agents Med Chem. 2018;18(6):865-874.
[2] Gajate C, Mollinedo F. Lipid rafts, endoplasmic reticulum and mitochondria in the antitumor action of the alkylphospholipid analog edelfosine. Anticancer Agents Med Chem. 2014 May;14(4):509-27.
[3] Tanzifi A, Khoshi A, Emami S, et al. The effect of edelfosine on GRA1 and MIC3 expressions in acute toxoplasmosis. Parasitol Res. 2020 Apr;119(4):1371-1380.
[4] Rai M, Rawat K, Muhammadi MK, et al. Edelfosine reactivates latent HIV-1 reservoirs in myeloid cells through activation of NF-κB and AP1 pathway. Virology. 2022 Sep;574:57-64.
[5] Dakir EH, Gajate C, Mollinedo F, et al. Antitumor activity of alkylphospholipid edelfosine in prostate cancer models and endoplasmic reticulum targeting. Biomed Pharmacother. 2023 Nov;167:115436.
[6] Shafer SH, Williams CL, et al. Non-small and small cell lung carcinoma cell lines exhibit cell type-specific sensitivity to edelfosine-induced cell death and different cell line-specific responses to edelfosine treatment. Int J Oncol. 2003 Aug;23(2):389-400.
[7] Alonso-Pérez V, Hernández V, Calzado MA, et al. Suppression of metastatic organ colonization and antiangiogenic activity of the orally bioavailable lipid raft-targeted alkylphospholipid edelfosine. Biomed Pharmacother. 2024 Feb;171:116149.
[8] Udayakumar TS, Stoyanova R, Shareef MM, et al. Edelfosine Promotes Apoptosis in Androgen-Deprived Prostate Tumors by Increasing ATF3 and Inhibiting Androgen Receptor Activity. Mol Cancer Ther. 2016 Jun;15(6):1353-63.
(R)-Edelfosine是一种属于具有抗肿瘤和抗寄生虫活性的合成脂质药物[1]。(R)-Edelfosine可通过靶向线粒体和脂筏上的FOF1-ATP合酶，诱导肿瘤细胞发生凋亡样细胞死亡[2]。(R)-Edelfosine表现出抗利什曼原虫和抗血吸虫活性[3]。(R)-Edelfosine还是一种新型HIV-1潜伏期逆转剂[4]。
在体外，(R)-Edelfosine（5-30μM）处理LNCaP、PC3和DU145前列腺癌细胞24-72小时，通过积累于内质网诱导内质网应激，显著促进caspase-3活化和PARP裂解，引发细胞凋亡[5]。(R)-Edelfosine（2.6-100μM）处理非小细胞肺癌细胞（NCI-H157、NCI-H520、NCI-H522）24-72小时，通过抑制磷脂酶C-B1活性诱导G2/M期阻滞和c-Jun氨基末端激酶活化，显著促进细胞凋亡和坏死[6]。
在体内，(R)-Edelfosine（30mg/kg）每日口服给药，用于处理尾静脉注射435-Lung-eGFP-CMV/Luc转移性癌细胞后5天开始直至12周的裸鼠，显著抑制了肺部和脑部的转移性肿瘤定植，同时延长了荷瘤小鼠的生存期[7]。(R)-Edelfosine（5-20mg/kg）每周三次口服给药，用于处理LNCaP细胞原位移植瘤模型小鼠，联合雄激素剥夺（双侧睾丸切除术）显著抑制了肿瘤体积增长[8]。