Acute promyelocytic leukemia (APL) is a severe type of acute leukemia and the prognosis of patients was poor. Indirubin is the active constituent of the traditional Chinese medicine qingdai and an indoline anti-tumor drug. N’-Acetylindirubin is a novel indirubin derivative with better curative effect and less side effect. In this study, the effects of N’-Acetylindirubin on proliferation, apoptosis and cell cycle of acute myeloid leukemia cell line HL-60 was examined. The results demonstrated that N’-Acetylindirubin significantly induced apoptotic cell death in a dose and time-dependent manner and arrested cell cycle in G2/M in HL-60 cells. N’-Acetylindirubin also suppressed cyclin D1. This study suggests that N’-Acetylindirubin may serves as a potential chemopreventive agent for acute promyelocytic leukemia.
References
[1]
Schwartsmann, G., Ratain, M.J., Cragg, G.M., et al. (2002) Anticancer Drug Discovery and Development throughout the World. J Clin Oncol, 20, 47S-59S.
[2]
Blazevic, T., Heiss, E.H., Atanasov, A.G., et al. (2015) Indirubin and Indirubin Derivatives for Counteracting Proliferative Diseases. Evid Based Complement Alternat Med, 2015, Article ID: 654098. https://doi.org/10.1155/2015/654098
[3]
Ma, M.Z. and Yao, B.Y. (1983) Progress in Indirubin Treatment of Chronic Myelocytic Leukemia. Journal of Traditional Chinese Medicine, 3, 245-248.
[4]
Zhang, Z.N., Liu, E.K., Zheng, T.L., et al. (1985) Treatment of Chronic Myelocytic Leukemia (CML) by Traditional Chinese Medicine and Western Medicine Alternately. Journal of Traditional Chinese Medicine, 5, 246-248.
[5]
Hoessel, R., Leclerc, S., Endicott, J.A., et al. (1999) Indirubin, the Active Constituent of a Chinese Antileukaemia Medicine, Inhibits Cyclin-Dependent Kinases. Nature Cell Biology, 1, 60-67. https://doi.org/10.1038/9035
[6]
Xiao, Z., Hao, Y., Liu, B., et al. (2002) Indirubin and Meisoindigo in the Treatment of Chronic Myelogenous Leukemia in China. Leukemia & Lymphoma, 43, 1763-1768. https://doi.org/10.1080/1042819021000006295
[7]
Karapetyan, G., Chakrabarty, K., Hein, M., et al. (2011) Synthesis and Bioactivity of Carbohy-drate Derivatives of Indigo, Its Isomers and Heteroanalogues. Chem Med Chem, 6, 25-37. https://doi.org/10.1002/cmdc.201000374
[8]
Vougogiannopoulou, K. and Skaltsounis, A.L. (2012) From Tyrian Purple to Kinase Modulators: Naturally Halogenated Indirubins and Synthetic Analogues. Planta Medica, 78, 1515-1528. https://doi.org/10.1055/s-0032-1315261
[9]
Wang, Y., Hoi, P.M., Chan, J.Y.W., et al. (2014) New Perspective on the Dual Functions of Indirubins in Cancer Therapy and Neuroprotection. Anti-Cancer Agents in Medicinal Chemistry, 14, 1213-1219.
https://doi.org/10.2174/1871520614666140825112924
[10]
Su, C.C., Lin, J.G., Li, T.M., et al. (2006) Curcumin-Induced Apoptosis of Human Colon Cancer Colo 205 Cells through the Production of ROS, Ca2+ and the Activation of Caspase-3. Anticancer Research, 26, 4379-4389.
[11]
Chen, J.C., Lu, K.W., Lee, J.H., et al. (2006) Gypenosides Induced Apoptosis in Human Colon Cancer Cells through the Mitochondria-Dependent Pathways and Activation of Caspase-3. Anticancer Research, 26, 4313-4326.
[12]
Alao, J.P. (2007) The Regulation of Cyclin D1 Degradation: Roles in Cancer Development and the Potential for Therapeutic Invention. Molecular Cancer, 6, 24.
https://doi.org/10.1186/1476-4598-6-24
