TY - JOUR
T1 - Constituents of Brazilian red propolis and their preferential cytotoxic activity against human pancreatic PANC-1 cancer cell line in nutrient-deprived condition
AU - Awale, Suresh
AU - Li, Feng
AU - Onozuka, Hiroko
AU - Esumi, Hiroyasu
AU - Tezuka, Yasuhiro
AU - Kadota, Shigetoshi
N1 - Funding Information:
We thank Nihon Propolis Co., Ltd. (Tokyo, Japan) for kindly providing the samples of Brazilian red propolis as well as for their continuous support in propolis research. This work was supported in part by a grant from the Ministry of Health and Welfare for the Second-Term Comprehensive 10-year Strategy for Cancer Control and Grants-in-Aid for Cancer Research from the Ministry of Health and Welfare.
PY - 2008/1/1
Y1 - 2008/1/1
N2 - 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 μg/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 μM. 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.
AB - 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 μg/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 μM. 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.
KW - 3,8-Dihydroxy-9-methoxypterocarpan
KW - Anti-austerity
KW - Anti-cancer agent
KW - PANC-1
KW - Pancreatic cancer
KW - Red propolis
KW - Screening strategy
UR - http://www.scopus.com/inward/record.url?scp=38049034385&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2007.10.004
DO - 10.1016/j.bmc.2007.10.004
M3 - 学術論文
C2 - 17950610
AN - SCOPUS:38049034385
SN - 0968-0896
VL - 16
SP - 181
EP - 189
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 1
ER -
