Liu Yang, Shin Dong-Yeop, Oh Somi, Kim Sujong, Koh Youngil, Kim Inho
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Pharmaceutical Division, Komipharm International Co., Ltd., Seoul, Republic of Korea.
Oncol Rep. 2017 Jul;38(1):481-487. doi: 10.3892/or.2017.5688. Epub 2017 Jun 1.
KML001 (NaAsO2, sodium metaarsenite, KOMINOX), a kind of arsenic compound, that has shown promising efficacy in non-Hodgkin's lymphoma (NHL) both in vitro and in vivo. In our study, the antileukemic effect of KML001 on acute lymphoid leukemia (ALL) and its mechanism of action were investigated. The results showed that KML001 inhibited cell proliferation in two types of ALL cell lines, CCRF-CEM and Molt-4. Exposure of ALL cells to KML001 induced apoptosis in a time-dependent manner. KML001 caused cell cycle arrest at G2/M phase instead of G0/G1 phase shown in other leukemia cells. In addition, we also tested the possibility of synergy of KML001 with doxercalciferol, a vitamin D2 derivative. Also, we found that a combination of KML001 with doxercalciferol showed a synergistic effect on ALL cell lines and this could be due to its different mechanism of action. Overall, our findings demonstrated KML001 could be a promising antileukemic agent especially when it is combined with doxercalciferol in ALL treatment.
KML001（偏亚砷酸钠，KOMINOX）是一种砷化合物，已在体外和体内实验中显示出对非霍奇金淋巴瘤（NHL）有良好疗效。在我们的研究中，研究了KML001对急性淋巴细胞白血病（ALL）的抗白血病作用及其作用机制。结果表明，KML001抑制了两种ALL细胞系CCRF-CEM和Molt-4的细胞增殖。ALL细胞暴露于KML001后会以时间依赖性方式诱导凋亡。KML001导致细胞周期停滞在G2/M期，而非其他白血病细胞中显示的G0/G1期。此外，我们还测试了KML001与维生素D2衍生物度骨化醇协同作用的可能性。并且，我们发现KML001与度骨化醇联合使用对ALL细胞系具有协同作用，这可能归因于其不同的作用机制。总体而言，我们的研究结果表明KML001可能是一种有前景的抗白血病药物，尤其是在ALL治疗中与度骨化醇联合使用时。
