Kurozu moromimatsu inhibits tumor growth of Lovo cells in a mouse model in vivo.
OBJECTIVE
In Japan, rice vinegar that has been matured and fermented for years in earthenware jars is considered a health food with anticolon cancer action. It is divided into the liquid component (Kurozu) and the sediment (Kurozu moromimatsu), which contains large amounts of organic materials and minerals. The effect of Kurozu moromimatsu (Kurozu-M) on cancer has not yet been examined. In this study, we examined the activity of Kurozu-M on colon cancer and investigated the mechanisms involved, focusing on active oxygen generation, apoptosis, and metalloproteinases (MMPs).


METHODS
We used Lovo cells transplanted into nude mice as an experimental model. We measured the tumor volume and MMP levels and conducted hematoxylin-eosin staining (for polymorphonuclear leukocytes), terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining (for apoptosis), and immunostaining for nitrotyrosine (a marker of active oxygen generation) in control, Kurozu-treated, and Kurozu-M--treated groups.


RESULTS
The tumor volume was the same in the control group (231 +/- 36 mm(3)) and Kurozu group (238 +/- 52 mm(3)), but was significantly reduced in the Kurozu-M group (152 +/- 28 mm(3), P < 0.001 versus control). Apoptosis of tumor cells and accumulation of polymorphonuclear leukocytes were not observed. Nitrotyrosine production, total MMP levels, and MMP activation were significantly reduced in the Kurozu-M group.


CONCLUSIONS
The administration of Kurozu-M prolonged the lifespan of cancer cell-transplanted mice, inhibited tumor progression, and reduced nitrotyrosine production and MMP activation, but did not induce apoptosis.
Fukuyama
Naoto
N
Department of Physiology, Tokai University, School of Medicine, Isehara, Kanagawa, Japan. fukuyama@is.icc.u-tokai.ac.jp
Jujo
Shio
S
Ito
Isao
I
Shizuma
Toru
T
Myojin
Kazunori
K
Ishiwata
Kazuo
K
Nagano
Masanobu
M
Nakazawa
Hiroe
H
Mori
Hidezo
H
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D005260:Female; D005285:Fermentation; D045726:Metalloproteases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012275:Oryza / Q000737:chemistry / Q000382:microbiology; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D011897:Random Allocation; D013047:Specific Pathogen-Free Organisms; D014443:Tyrosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D000970:Antineoplastic Agents; D010936:Plant Extracts; C002744:3-nitrotyrosine; D014443:Tyrosine; D045726:Metalloproteases