L-Selenocystine is an oxidation diselenide product of selenocysteine with strong antioxidant activity [1]. L-Selenocystine can promote the phosphorylation of JNK, p38 MAPK, ERK and Akt in cells, and induce the activation of caspase, PARP cleavage and DNA fragmentation [2]. L-Selenocystine has been widely used to induce apoptosis in various cancer cells and to generate reactive oxygen species (ROS)[3].
In vitro, L-Selenocystine treatment for 24 hours significantly inhibited the proliferation of HepG2 cells and L02 cells, with IC50 values of 71.880μM and 5.444μM, respectively[4]. Treatment with 50μM L-Selenocystine for 24 hours significantly inhibited the activation of Nrf2 and the nuclear translocation of downstream proteins in WiDr cells, and induced autophagy in the cells[5]. The combined treatment of 10μM L-Selenocystine and 5-fluorouracil (400μM) for 24 hours triggered mitochondrial-mediated apoptosis in A375 cells, inducing mitochondrial dysfunction and enhancing DNA damage[6].
In vivo, L-Selenocystine treatment via vein injection at a dose of 10mg/kg/day for 14 days effectively suppressed JEG-3 choriocarcinoma tumor xenograft growth in mice[7]. Every other day, 5mg/kg dose of L-Selenocystine and 2mg/kg dose of auranofin were injected via the tail vein for 16 days, which inhibited the tumor volume and weight of A549 human lung adenocarcinoma xenografts in nude mice, without affecting the body weight of the mice[8].
References:
[1] Chuai H, Zhang S Q, Bai H, et al. Small molecule selenium-containing compounds: Recent development and therapeutic applications[J]. European journal of medicinal chemistry, 2021, 223: 113621.
[2] Chen T, Wong Y S. Selenocystine induces S-phase arrest and apoptosis in human breast adenocarcinoma MCF-7 cells by modulating ERK and Akt phosphorylation[J]. Journal of agricultural and food chemistry, 2008, 56(22): 10574-10581.
[3] Chen T, Wong Y S. Selenocystine induces reactive oxygen species–mediated apoptosis in human cancer cells[J]. Biomedicine & Pharmacotherapy, 2009, 63(2): 105-113.
[4] Chen H, Su J, Chen D, et al. L-Selenocystine induce HepG2 cells apoptosis through ROS-mediated signaling pathways[J]. Biocell, 2022, 46(10): 2267.
[5] Hsu W L, Wang C M, Yao C L, et al. Blockage of Nrf2 and autophagy by L-selenocystine induces selective death in Nrf2-addicted colorectal cancer cells through p62-Keap-1-Nrf2 axis[J]. Cell Death & Disease, 2022, 13(12): 1060.
[6] Fan C, Chen J, Wang Y, et al. Selenocystine potentiates cancer cell apoptosis induced by 5-fluorouracil by triggering reactive oxygen species-mediated DNA damage and inactivation of the ERK pathway[J]. Free Radical Biology and Medicine, 2013, 65: 305-316.
[7] Zhao M, Hou Y, Fu X, et al. Selenocystine inhibits JEG-3 cell growth in vitro and in vivo by triggering oxidative damage-mediated S-phase arrest and apoptosis[J]. Journal of Cancer Research and Therapeutics, 2018, 14(7): 1540-1548.
[8] Fan C, Zheng W, Fu X, et al. Enhancement of auranofin-induced lung cancer cell apoptosis by selenocystine, a natural inhibitor of TrxR1 in vitro and in vivo[J]. Cell death & disease, 2014, 5(4): e1191-e1191.
L-Selenocystine是selenocysteine的氧化二硒化物产物，具有强抗氧化活性[1]。L-Selenocystine能促进细胞内JNK、p38 MAPK、ERK和Akt的磷酸化，并诱导caspase激活、PARP裂解和DNA片段化[2]。L-Selenocystine已被广泛用于诱导多种癌细胞凋亡和产生活性氧（ROS）[3]。
在体外，L-Selenocystine处理24小时显著抑制了HepG2细胞和L02细胞的增殖，IC50值分别为71.880µM和5.444µM[4]。使用50µM的L-Selenocystine处理24小时，显著抑制了WiDr细胞中Nrf2的激活及下游蛋白的核转位，并诱导了细胞自噬[5]。联合使用10µM的L-Selenocystine和5-氟尿嘧啶（400 µM）处理24小时，引发了A375细胞中线粒体介导的凋亡，诱导线粒体功能障碍并增强了DNA损伤 [6]。
在体内，每日静脉注射10mg/kg剂量的L-Selenocystine，持续14天，有效抑制了小鼠体内JEG-3绒毛膜癌异种移植瘤的生长[7]。每隔一天通过尾静脉注射5mg/kg剂量的L-Selenocystine和2mg/kg剂量的金诺芬，持续16天，抑制了裸鼠中A549人肺腺癌异种移植瘤的体积和重量，且未影响小鼠的体重[8]。