Up-regulation of matrix metalloproteinase family gene involvement in ursolic acid-induced human lung non-small carcinoma cell apoptosis.
Ursolic acid is a triterpenoid reported to inhibit the invasion of cancer cells. In this study, there was a significant increase in the gene expression of matrix metalloproteinase (MMP)-1, -2 -3, -9 and -10 in H460 cells after treatment with 10 microM ursolic acid for 24 h. Under these experimental conditions, it was found that ursolic acid induced H460 cell apoptosis. These results indicated that matrix metalloproteinase family members are involved not only in invasion, but also in apoptosis of cancer cells. It has been suggested that ursolic acid acts via a glucocorticoid receptor in the regulation of MMP. Our study also demonstrated that the localization of glucocorticoid receptor in the cytosol might be an important factor of MMP up-regulation during ursolic acid-induced H460 cell apoptosis. Ursolic acid induced a typical apoptosis on H460 cells, which was characterized by the activation of caspase-3, nuclear morphological changes and DNA fragmentation.
Lai
Miao Y
MY
School of Pharmacy, China Medical University, Taichung, Taiwan, ROC.
Leung
Henry Wing C
HW
Yang
Wen H
WH
Chen
Wen H
WH
Lee
Hong Z
HZ
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D016196:S Phase / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D000097245:Ursolic Acid
D000972:Antineoplastic Agents, Phytogenic; D007527:Isoenzymes; D020782:Matrix Metalloproteinases; D011965:Receptors, Glucocorticoid; D014315:Triterpenes; D000097245:Ursolic Acid