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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3312-3318.
Prepublished online as a Blood First Edition Paper on December 30, 2004; DOI 10.1182/blood-2004-10-3915.
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Submitted October 12, 2004
Accepted December 23, 2004
Baicalein, a component of Scutellaria Radix, identified from Huang-Liang-Jie-Du-Tang ( HLJDT) leads to suppression of proliferation and induction of apoptosis in human myeloma cells
Zi Ma, Ken-ichiro Otsuyama, Shangqin Liu, Saeid Abroun, Hideaki Ishikawa, Naohiro Tsuyama, Masanori Obata, Fu-jun Li, Xu Zheng, Yasuko Maki, Koji Miyamoto, and Michio M Kawano*
Department of Bio-Signal Analysis, AMES, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, Japan
Department of Kampo Medicine, Molecular Science and Applied Medicine, Yamaguchi University School of Medicine, Yamaguchi University, Ube, Yamaguchi, Japan
* Corresponding author; email: mkawano{at}yamaguchi-u.ac.jp.
In the search for a more effective adjuvant therapy to treat multiple myeloma(MM), we investigated the effects of the traditional Chinese herbal medicines Huang-Liang-Jie-Du-Tang (HLJDT), Gui-Zhi-Fu-Ling-Wan (GZFLW) and Huang-Lian-Tang (HLT) on the proliferation and apoptosis of myeloma cells. HLJDT inhibited the proliferation of myeloma cell lines and the survival of primary myeloma cells, especially MPC-1- immature myeloma cells, and induced apoptosis in myeloma cell lines via a mitochondria-mediated pathway; by reducing mitochondrial membrane potential and activating caspase-9 and caspase-3. Further experiments confirmed that Scutellaria Radix was responsible for the suppressive effect of HLJDT on myeloma cell proliferation, and the baicalein in Scutellaria Radix showed strong growth inhibition and induction of apoptosis in comparison with baicalin or wogonin. Baicalein as well as baicalin suppressed the survival in vitro of MPC-1- immature myeloma cells rather than MPC-1+ myeloma cells from myeloma patients. Baicalein inhibited the phosphorylation of IkB- , which was followed by decreased expression of the IL-6 and XIAP genes and activation of caspase-9 and caspase-3. Therefore, HLJDT and Scutellaria Radix have an anti-proliferative effect on myeloma cells, especially MPC-1- immature myeloma cells, and baicalein may be responsible for the suppressive effect of Scutellaria Radix by blocking IkB- degradation.
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