Lukasheva Elena V, Babayeva Gulalek, Karshieva Saida Sh, Zhdanov Dmitry D, Pokrovsky Vadim S
Department of Biochemistry, Peoples' Friendship University of Russia (RUDN University), Miklukho-Maklaya Street 6, 117198 Moscow, Russia.
Laboratory of Combined Treatment, N.N. Blokhin Cancer Research Center, Kashirskoe Shosse 24, 115478 Moscow, Russia.
Pharmaceuticals (Basel). 2021 Oct 22;14(11):1070. doi: 10.3390/ph14111070.
L-lysine α-oxidase (LO), one of L-amino acid oxidases, deaminates L-lysine with the yield of HO, ammonia, and α-keto-ε-aminocaproate. Multiple in vitro and in vivo studies have reported cytotoxic, antitumor, antimetastatic, and antitumor activity of LO. Unlike asparaginase, LO has a dual mechanism of action: depletion of L-lysine and formation of HO, both targeting tumor growth. Prominent results were obtained on murine and human tumor models, including human colon cancer xenografts HCT 116, LS174T, and T47D with maximum T/C 12, 37, and 36%, respectively. The data obtained from human cancer xenografts in immunodeficient mice confirm the potential of LO as an agent for colon cancer treatment. In this review, we discuss recently discovered molecular mechanisms of biological action and the potential of LO as anticancer enzyme.
L-赖氨酸α-氧化酶(LO)是L-氨基酸氧化酶之一,可使L-赖氨酸脱氨,生成过氧化氢、氨和α-酮-ε-氨基己酸。多项体外和体内研究报道了LO的细胞毒性、抗肿瘤、抗转移和抗肿瘤活性。与天冬酰胺酶不同,LO具有双重作用机制:消耗L-赖氨酸并生成过氧化氢,两者均靶向肿瘤生长。在小鼠和人类肿瘤模型上取得了显著成果,包括人结肠癌异种移植瘤HCT 116、LS174T和T47D,最大T/C分别为12%、37%和36%。从免疫缺陷小鼠体内人癌异种移植瘤获得的数据证实了LO作为结肠癌治疗药物的潜力。在本综述中,我们讨论了最近发现的生物学作用分子机制以及LO作为抗癌酶的潜力。