Aqueous extract of Magnolia officinalis mediates proliferative capacity, p21WAF1 expression and TNF-alpha-induced NF-kappaB activity in human urinary bladder cancer 5637 cells; involvement of p38 MAP kinase.
Magnolia officinalis is a commonly used herb in East Asian countries and has multiple pharmacological effects. Although Magnolia officinalis has a variety of pharmacological effects on certain cancer cell types, the molecular mechanisms on urinary bladder cancer are unclear. An aqueous extract of M. officinalis inhibited cell proliferation in cultured human urinary bladder cancer 5637 cells. Inhibition of proliferation was associated with G1 cell cycle arrest. Treatment with M. officinalis extract blocked the cell cycle in the G1 phase, down-regulated the expression of cyclins and CDKs and up-regulated the expressions of p21WAF1 and p27 Kip1, which are CDK inhibitors. In addition, M. officinalis extract induced a marked activation of p38 MAP kinase and JNK. SB203580, a p38 MAP kinase specific inhibitor, blocked the expression of M. officinalis extract-dependent p38 MAP kinase and p21WAF1. Blockage of the p38 MAPK kinase function reversed M. officinalis extract-induced cell proliferation. These data demonstrate that M. officinalis extract-induced cell growth inhibition appears to be linked to the activation of p38 MAP kinase through p21WAF1 expression. Moreover, treatment of 5637 cells with M. officinalis extract suppressed constitutive and TNF-alpha-induced-nuclear factor-kappa B (NF-kappaB) activation. Furthermore, the transactivation of TNF-alpha-stimulated NF-kappaB was inhibited by SB203580 treatment. Collectively, these results suggest that the p38 MAP kinase pathway contributes, at least partially, to the anti-cancer activity of M. officinalis extract in human urinary bladder tumor 5637 cells.
Lee
Se-Jung
SJ
Department of Food and Biotechnology, Chungju National University, Chungbuk, Korea.
Kim
Hong-Man
HM
Cho
Young-Hwa
YH
Park
Keerang
K
Kim
Eun-Jung
EJ
Jung
Kyung-Hwan
KH
Kim
Cheorl-Ho
CH
Kim
Wun-Jae
WJ
Moon
Sung-Kwon
SK
D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D031566:Magnolia; D016328:NF-kappa B / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D001749:Urinary Bladder Neoplasms; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016328:NF-kappa B; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases