New synthetic flavone derivatives induce apoptosis of hepatocarcinoma cells.
Natural flavonoids have broad biological activity, including anticancer. In this study, a series of novel flavone derivatives were synthesized with the substitutions of chlorine, isopropyl, methoxy, and nitro groups on the benzene ring of flavone skeleton to develop effective anticancer agents. Antiproliferative assays showed that the synthesized chemicals possess notable activity against hepatocarcinoma cells (HepG-2); in particular, the compound 6f with chlorine and dimethoxy modifications at the two benzene rings showed an IC(50) at 1.1 microM to HepG-2. The 6f also displayed marked anticancer activity towards a panel of cancer cells, including nasopharyngeal carcinoma cells (CNE-2 and CNE-1), breast adenocarcinoma cell (MCF-7), and epithelial carcinoma cells (Hela). Exposing HepG-2 cells to compound 6f at 10 microM induced chromatin condensation, nuclear disassembly, and DNA fragmentation. In 6f-treated HepG-2 cells, the sub-G(0) population was remarkably increased; and in these cells, both caspase-8 and caspase-9 activity was significantly increased, which in turn activated caspase-3. In addition, proapoptotic Bax was upregulated by compound 6f while the antiapoptotic Bcl-2 was downregulated. Taken together, our data suggest that the new flavonoid derivative 6f triggers apoptosis through both death-receptor and mitochondria-dependent intrinsic pathways, being a potent therapeutic agent against hepatocarcinoma.
Liu
Huachen
H
The Key Laboratory of Chemical Biology, Guangdong Province, Graduate School at Shenzhen, Tsinghua University, Lishui Road, Shenzhen 518055, PR China.
Dong
Aijun
A
Gao
Chunmei
C
Tan
Chunyan
C
Xie
Zhenhua
Z
Zu
Xuyu
X
Qu
Long
L
Jiang
Yuyang
Y
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D047309:Flavones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D047309:Flavones