Andrographolide, isolated from Andrographis paniculata, induces apoptosis in monocytic leukemia and multiple myeloma cells via augmentation of reactive oxygen species production [version 2; peer review: 2 approved]

F1000Research

Itsuro Katsuda¹  Yuki Higashimoto²  Tamae Ohye²  Seiji Imamura²  Hidehiko Akiyama³  Taei Matsui³  Atsushi Ogasawara³  Hiromu Takematsu³  Hiroki Doi³  Johannes M. Dijkstra⁴ 

[1] Department of Hematology, Fujita Health University School of Medicine, Toyoake, 470-1192, Japan;Faculty of Medical Technology, Fujita Health University School of Medical Sciences, Toyoake, 470-1192, Japan;Field of Clinical Laboratory Sciences, Fujita Health University Graduate School of Health Sciences, Toyoake, 470-1192, Japan;Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, 470-1192, Japan;

关键词: Andrographis paniculata;    andrographolide;    apoptosis;    reactive oxygen species;    monocytic leukemia cells;    multiple myeloma cells;    eng;   

DOI  :  

来源: DOAJ

【 摘 要 】

Background: Andrographolide (Andro) is a diterpenoid component of the plant Andrographis paniculata that is known for its anti-tumor activity against a variety of cancer cells.   Methods: We studied the effects of Andro on the viability of the human leukemia monocytic cell line THP-1 and the human multiple myeloma cell line H929. Andro was compared with cytosine arabinoside (Ara-C) and vincristine (VCR), which are well-established therapeutics against hematopoietic tumors. The importance of reactive oxygen species (ROS) production for the toxicity of each agent was investigated by using an inhibitor of ROS production, N-acetyl-L-cysteine (NAC).    Results:  Andro reduced the viability of THP-1 and H929 in a dose-dependent manner. H929 viability was highly susceptible to Andro, although only slightly susceptible to Ara-C. The agents Andro, Ara-C, and VCR each induced apoptosis, as shown by cellular shrinkage, DNA fragmentation, and increases in annexin V-binding, caspase-3/7 activity, ROS production, and mitochondrial membrane depolarization. Whereas Ara-C and VCR increased the percentages of cells in the G0/G1 and G2/M phases, respectively, Andro showed little or no detectable effect on cell cycle progression. The apoptotic activities of Andro were largely suppressed by NAC, an inhibitor of ROS production, whereas NAC hardly affected the apoptotic activities of Ara-C and VCR.  Conclusions: Andro induces ROS-dependent apoptosis in monocytic leukemia THP-1 and multiple myeloma H929 cells, underlining its potential as a therapeutic agent for treating hematopoietic tumors. The high toxicity for (thus forming: The high toxicity for H929 cells, by a mechanism that is different from that of Ara-C and VCR, is encouraging for further studies on the use of Andro against multiple myeloma.) H929 cells, by a mechanism that is different from that of Ara-C and VCR, is encouraging for further studies on the use of Andro against multiple myeloma.

【 授权许可】

Unknown