Inhibition of tumor growth and angiogenesis by water extract of Gac fruit (Momordica cochinchinensis Spreng).
The antitumor activity of the crude water extract from Gac fruit (Momordica cochinchinensis) was investigated in vivo and in vitro. A water extract prepared from 0.75 and 0.25 mg dry weight of Gac fruit per gram body weight was given daily to Balb/c mice (n=15/group). The water extract inhibited the growth of the colon 26-20 adenocarcinoma cell line, transplanted in Balb/c mice, reducing wet tumor weight by 23.6%. Histological and immunohistochemical results indicated that Gac water extract reduced the density of blood vessels around the carcinoma. The water extract also produced a marked suppression of cell proliferation in colon 26-20 and HepG2 cells. Cell cycle analysis demonstrated a significant accumulation of cells in the S phase by water extract. Immunoblotting showed that cyclin A, Cdk2, p27waf1/Kip1 were down-regulated, whereas the protein level of p21waf1/Cip1 was not decreased. Treatment of colon 26-20 cells with Gac extract induced necrosis rather than apoptosis. The antitumor component was confirmed as a protein with molecular weight of 35 kDa, retained in the water-soluble high molecular weight fraction. Thus, the bioactive antitumor compound in Gac extract is a protein, which is distinct from lycopene, another compound in Gac fruit with potential antitumor activity.
Tien
Pham Gia
PG
Department of Integrated Medicine 1, Jichi Medical School, Omiya Medical Center, 1-847 Amanuma-cho, Saitama 330-8503, Japan.
Kayama
Fujio
F
Konishi
Fumio
F
Tamemoto
Hiroyuki
H
Kasono
Keizo
K
Hung
Nguyen Thi Kim
NT
Kuroki
Masatoshi
M
Ishikawa
San-E
SE
Van
Chuyen Nguyen
CN
Kawakami
Masanobu
M
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000473:pathology*; D019925:Cyclin A / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D015536:Down-Regulation; D004354:Drug Screening Assays, Antitumor; D015151:Immunoblotting; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D029775:Momordica / Q000737:chemistry*; D009336:Necrosis; D009389:Neovascularization, Pathologic; D010936:Plant Extracts / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014867:Water / Q000737:chemistry
C493957:Cdkn1a protein, mouse; D018797:Cell Cycle Proteins; D019925:Cyclin A; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010936:Plant Extracts; D014867:Water