Abstract:
: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 microg/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 (PC(100)) at the concentration of 12.5 microM. 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.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Awale S,Li F,Onozuka H,Esumi H,Tezuka Y,Kadota Sdoi
10.1016/j.bmc.2007.10.004subject
Has Abstractpub_date
2008-01-01 00:00:00pages
181-9issue
1eissn
0968-0896issn
1464-3391pii
S0968-0896(07)00846-2journal_volume
16pub_type
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