Inhibitory effects of the aqueous extract of Magnolia officinalis on the responses of human urinary bladder cancer 5637 cells in vitro and mouse urinary bladder tumors induced by N-Butyl-N-(4-hydroxybutyl) nitrosamine in vivo.
This study investigated the anticancer activity of Magnolia officinalis on urinary bladder cancer in vitro and in vivo, and elucidated the mechanism of its activity. An aqueous extract of M. officinalis inhibited cell viability and DNA synthesis in cultured human urinary bladder cancer 5637 cells. Inhibition of proliferation was the result of apoptotic induction, because FACS analyses of 5637 cells treated with M. officinalis showed a sub-G1 phase accumulation. M. officinalis extract also increased cytoplasmic DNA-histone complex dose-dependently. These inhibitory effects were associated with the upregulation of proapoptotic molecules Bax, cytochrome c and caspase 3. Treatment of 5637 cells with M. officinalis extract suppressed the expression of matrix metalloproteinase 2 (MMP-2) and MMP-9, as revealed by zymographic and immunoblot analyses. When M. officinalis extract was given to mice simultaneously with the carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine, which induces urinary bladder tumors, the size of the induced tumors was smaller. Finally, histological data indicated that the histological grade of carcinoma and the depth of invasion were dramatically decreased by treatment with M. officinalis extract in mice with N-butyl-N-(4-hydroxybutyl) nitrosamine-induced urinary bladder tumors. In conclusion, the findings showed that M. officinalis extract exhibited potential chemopreventive activity against urinary bladder tumor in vitro and in vivo.
Lee
Se-Jung
SJ
Department of Food and Biotechnology, Chungju National University, Chungju, Chungbuk 380-702, South Korea.
Cho
Young-Hwa
YH
Park
Keerang
K
Kim
Eun-Jung
EJ
Kang
Bong-Su
BS
Jung
Kyung-Hwan
KH
Kim
Cheorl-Ho
CH
Kim
Wun-Jae
WJ
Moon
Sung-Kwon
SK
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002085:Butylhydroxybutylnitrosamine / Q000633:toxicity*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D031566:Magnolia / Q000737:chemistry*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000188:drug therapy*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D016588:Anticarcinogenic Agents; D019384:Nucleic Acid Synthesis Inhibitors; D010936:Plant Extracts; D051028:bcl-2-Associated X Protein; D002085:Butylhydroxybutylnitrosamine; D045304:Cytochromes c; D004247:DNA; D053148:Caspase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9