Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism

Wiley - Tập 18 Số 14 - Trang 1670-1681 - 2004
Tae‐Wook Chung1, Sung‐Kwon Moon2,1, Young‐Chae Chang3, Jeong‐Heon Ko4, Young‐Choon Lee5, Gun Rae Cho6, Soo‐Hyun Kim6, Jong‐Guk Kim7, Cheorl‐Ho Kim1
1National Research Laboratory for Glycobiology and Department of Biochemistry and Molecular Biology Dongguk University College of Oriental Medicine Kyungju Kyungbuk Korea
2Chunju National University Chungbuk Korea
3Department of Pathology, College of Medicine, Daegu Catholic University, Daegu, Korea
4Proteome Research Korea Research Institute of Bioscience and Biotechnology Daejon Korea
5Faculty of Biotechnology Dong‐A University Pusan Korea
6Proteome Analysis Team Korea Basic Science Research Institute Daejon Korea
7Department of Microbiology, Kyungpook National University, Daegu, Korea

Tóm tắt

ABSTRACTOur previous studies have clearly shown that the angiogenic enzymes, matrix metalloproteinase (MMP) ‐2/9, are directly involved in human hepatic tumorigenesis and metastasis and suggest that the MMP‐2/9 inhibitors, which have dual inhibitory activi¬ties on enzyme activity and transcription, represent the best candidates for achieving tumor regression. Many anti‐cancer drugs have strong cellular cytotoxicity and side effects, indicating that strong anti‐cancer drugs that have no or minimal cytotoxicity and side effects need to be developed. The specific aim of the present study was to develop powerful anti‐cancer drugs with specific tumor regression and anti‐metastatic potential having the dual inhibitory activities of specific MMP‐2 and ‐9 enzyme activities and gene transcription at the molecular level. Caffeic acid (CA), a strong and selective MMP‐9 activity and transcription inhibitor, was isolated from the plant Euonymus alatus and its derivative, caffeic acid phenethyl ester (CAPE), was synthesized. CA and CAPE selectively inhibited MMP‐2 and ‐9 but not ‐1, ‐3, ‐7, or cathepsin K. Treatment of HepG2 cells with CA (100 μg/mL) and CAPE (5 μg/mL) suppressed phorbol 12‐myristate 13‐acetate (PMA) ‐in¬duced MMP‐9 expression by inhibiting the function of NF‐κB, but not AP‐1. We confirmed that CA and CAPE suppressed the growth of HepG2 tumor xenografts in nude mice in vivo. The subcutaneous and oral administrations of CA and CAPE significantly reduced the liver metastasis. These results confirm the therapeutic potential of the compounds and suggest that the antimetastatic and anti‐tumor effects of CA and CAPE are mediated through the selective suppression of MMP‐9 enzyme activity and transcriptional down‐regulation by the dual inhibition of NF‐κB as well as MMP‐9 catalytic activity.—Chung, T.‐W., Moon, S.‐K., Chang, Y.‐C., Ko, J.‐H., Lee, Y.‐C., Cho, G., Kim, S.‐H., Kim, J.‐G., Kim, C.‐H. Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism. FASEBJ. 18, 1670–1681 (2004)

Từ khóa


Tài liệu tham khảo

10.1096/fasebj.5.8.1850705

10.1016/S0945-053X(97)90028-7

10.1200/JCO.2000.18.5.1135

10.1016/S0003-9861(02)00522-2

Chung T. W., 2003, Hepatitis B virus X protein modulates the expression of PTEN by inhibiting the function of p53, a transcriptional activator in liver cells, Cancer Res., 63, 3453

Kohn E. C., 1995, Molecular insights into cancer invasion: strategies for prevention and intervention, Cancer Res., 55, 1856

10.1054/bjoc.2001.1810

Sugita K., 1999, Recent advances in inhibitors of metalloproteinases for cancer therapy, I Drugs, 2, 327

10.2165/00126839-199901020-00001

10.1517/13543784.9.9.2167

Gatto C., 1999, BAY 12-9566, a novel inhibitor of matrix metalloproteinases with antiangiogenic activity, Clin. Cancer Res., 5, 3603

Lozonschi L., 1999, Controlling tumor angiogenesis and metastasis of C26 murine colon adenocarcinoma by a new matrix metalloproteinase inhibitor, KB-R7785, in two tumor models, Cancer Res., 59, 1252

10.1021/jm9707582

Maekawa R., 1999, Correlation of antiangiogenic and antitumor efficacy of N-biphenyl sulfonyl-phenylalanine hydroxiamic acid (BPHA), an orally-active, selective matrix metalloproteinase inhibitor, Cancer Res., 59, 1231

10.1016/S0304-3835(01)00837-0

10.1002/glia.10255

10.1096/fj.03-1429fje

10.1038/sj.onc.1200973

10.4049/jimmunol.165.10.5788

10.1053/jhep.2002.32676

10.1096/fj.01-0198com

Sato T., 2002, Inhibition of activator protein-1 binding activity and phosphatidylinositol 3-kinase pathway by nobiletin, a polymethoxy flavonoid, results in augmentation of tissue inhibitor of metalloproteinases-1 production and suppression of production ofmatrix metalloproteinases-1 and -9 in human fibrosarcoma HT-1080 cells, Cancer Res., 62, 1025

10.1038/sj.onc.1203239

10.1038/sj.leu.2402482

10.1126/science.281.5383.1680

10.1038/sj.onc.1205483

10.1128/MCB.19.8.5785

10.1093/carcin/21.5.871

Kaegi E., 1998, Unconventional therapies for cancer: 2. Green tea. The task force on alternative therapies of the Canadian breast cancer research initiative, Can. Med. Assoc. J., 158, 1033

10.1016/S0167-4838(00)00009-1

10.1016/S0378-8741(02)00373-2

Shahidi F., 1995, Food Phenolics. Sources, Chemistry, Effects, Applications

10.1007/BF01941717

10.1016/S0968-0896(02)00138-4

10.1016/S0006-2952(97)00470-X

10.1016/0005-2760(84)90287-X

10.1016/0014-5793(96)01111-8

Michaluart P., 1999, Inhibitory effects of caffeic acid phenethyl ester on the activity and expression of cyclooxygenase-2 in human oral epithelial cells and in a rat model of inflammation, Cancer Res., 59, 2347

Chan W. S., 1995, Structureactivity relationship of caffeic acid analogues on xanthine oxidase inhibition, Anticancer Res., 15, 703

Schefferlie J. G., 1993, In vitro and in vivo reversible and irreversible inhibition of rat glutathione S-transferase isoenzymes by caffeic acid and its 2-S-glutathionyl conjugate, Food Chem. Toxicol., 31, 475, 10.1016/0278-6915(93)90106-9

10.1093/carcin/14.7.1321

Frenkel K., 1993, Inhibition of tumor promoter-mediated processes in mouse skin and bovine lens by caffeic acid phenethyl ester, Cancer Rees., 53, 1255

10.1111/j.2042-7158.1998.tb03332.x

10.1021/np50117a007

10.1073/pnas.90.6.2399

10.1016/S0891-5849(00)00515-3

10.1073/pnas.93.17.9090

10.1248/bpb.26.638

10.1016/j.intimp.2003.08.003

10.1007/s002800051097

10.1111/j.1699-0463.1999.tb01535.x

10.1056/NEJM199512283332608

10.1172/JCI6870

10.1002/hep.510240206

Sakamoto Y., 2000, Overexpression of MMP-9 correlates with growth of small hepatocellular carcinoma, Int. J. Oncol., 17, 237

10.1002/(SICI)1097-0215(19990301)80:5<764::AID-IJC22>3.0.CO;2-J

10.1007/BF00690603

Nemunaitis J., 1998, Combined analysis of studies of the effects of the matrix metalloproteinase inhibitor marimastat on serum tumor markers in advanced cancer: selection of a biologically active and tolerable dose for longer-term studies, Clin. Cancer Res., 4, 1101

Lyons J. G., 1993, Interleukin-1 beta and transforming growth factor-alpha/epidermal growth factor induce expression of M(r) 95,000 type IV collagenase/gelatinase and interstitial fibroblast-type collagenase by rat mucosal keratinocytes, J. Biol. Chem., 268, 19143, 10.1016/S0021-9258(17)46745-7

10.1016/S0014-5793(98)01034-5

10.1016/S0006-291X(03)00788-5

10.1073/pnas.88.3.966

10.1016/S0945-053X(97)90026-3

10.1101/gad.7.11.2064

10.1126/science.281.5381.1360

Thông tin
Thông tin xuất bản

Wiley

Tập 18 Số 14

1670-1681

Thông tin tác giả