Anti-tumor effects of paeonol in a HepA-hepatoma bearing mouse model via induction of tumor cell apoptosis and stimulation of IL-2 and TNF-alpha production.
Paeonol, a phenolic component from the root bark of Paeonia moutan, is traditionally used as a Chinese herbal medicine to activate the blood flow and remove blood stasis. Evidence shows that paeonol have anti-tumor, anti-inflammatory, and analgesic effects; however, the underlying mechanisms remain unknown. In this study, we investigated the molecular mechanisms by which paeonol exerts the anti-tumor effects by using a murine model of hepatoma established by in vivo injection of mouse HepA-hepatoma cells. Treatment of mice with 100, 200, or 400 mg/kg/day of paeonol significantly inhibited the growth of the HepA tumor in mice, induced HepA cell apoptosis as demonstrated by light microscopy and electron microscopy analyses, decreased the expression of Bcl-2 and increased the expression of Bax in HepA tumor tissues in a dose-related manner. Administration of paeonol in vivo also elevated serum levels of IL-2 and TNF-alpha in tumor-bearing mice. Moreover, splenocytes and macrophages isolated from paeonol-treated HepA tumor-bearing mice produced higher levels of IL-2 and TNF-alpha in response to concanavalin A and lipopolysaccharide stimulation, respectively, compared to these isolated from non-treated HepA tumor-bearing mice. In vitro treatment with paeonol was able to directly stimulate IL-2 and TNF-alpha production in splenocytes and macrophages from tumor-bearing mice, respectively. In conclusion, paeonol has the anti-tumor effect against hepatoma cells, which are likely mediated via induction of tumor cell apoptosis and stimulation of IL-2 and TNF-alpha production. Paeonol could be a promising drug to treat hepatocellular carcinoma.
Sun
Guo-Ping
GP
Department of Oncology, The First Affiliated Hospital of Anhui Medical University; Hefei, 230032, China. sunguoping@ahmu.edu.cn
Wang
Hua
H
Xu
Shu-Ping
SP
Shen
Yu-Xian
YX
Wu
Qiang
Q
Chen
Zhen-Dong
ZD
Wei
Wei
W
D000098:Acetophenones / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007376:Interleukin-2 / Q000097:blood / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000098:Acetophenones; D000972:Antineoplastic Agents, Phytogenic; C494827:Bax protein, mouse; D007376:Interleukin-2; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; C013638:paeonol