Constituents of Brazilian red propolis and their preferential cytotoxic activity against human pancreatic PANC-1 cancer cell line in nutrient-deprived condition

被引:122
作者
Awale, Suresh [1 ]
Li, Feng [1 ]
Onozuka, Hiroko [2 ]
Esurni, Hiroyasu [2 ]
Tezuka, Yasuhiro [1 ]
Kadota, Shigetoshi [1 ]
机构
[1] Toyama Univ, Ins Nat Med, Toyama 9300194, Japan
[2] Natl Canc Ctr Res Inst E, Invest Treatment Div, Chiba 2778577, Japan
关键词
D O I
10.1016/j.bmc.2007.10.004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human pancreatic cancer cells such as PANC-1 are known to exhibit marked tolerance to nutrition starvation that enables them to survive for prolonged period of time even under extremely nutrient-deprived conditions. Thus, elimination of this tolerance to nutrition starvation is regarded as a novel approach in anticancer drug development. In this study, the MeOH soluble extract of Brazilian red propolis was found to kill 100%, PANC-1 cells preferentially in the nutrient-deprived condition at the concentration of 10 mu g/mL. Further phytochemical investigation led to the isolation of 43 compounds including three new compounds, (6aS,11aS)-6a-ethoxymedicarpan (1), 2-(2',4'-dihydroxyphenyl)-3-methyl-6-methoxybenzofuran (2), and 2,6-dihydroxy-2-[(4-hydroxyphenyl)methyl]-3-benzofuranone (3). Among them, (6aR,11aR)-3,8-dihydroxy-9-methoxypterocarpan (21, DMPC) displayed the most potent 100% preferential cytotoxicity (PC100) at the concentration of 12.5 mu M. Further study on the mode of cell death induced by DMPC against PANC-1 cells indicated that killing process was not accompanied by DNA fragmentation, rather through a nonapoptotic pathway accompanied by necrotic-type morphological changes. (C) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:181 / 189
页数:9
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