Antitumor activities of a newly synthesized shikonin derivative, 2-hyim-DMNQ-S-33.
2- or 6-(1-hydroxyiminoalkyl)-5,8-dimethoxy-1, 4-naphthoquinone(2- or 6-hyim-DMNQ) derived from the roots of Lithospermum erythrorhizon was synthesized for the evaluation of antitumor activities. Among those derivatives, 2-hyim-DMNQ-S33 was found to be a potent anticancer agent. This compound suppressed the proliferation of Radiation Induced Fibrosarcoma (RIF) cells in a dose-dependent manner. 2-hyim-DMNQ-S33 significantly prolonged the survival time by 239% as compared with Sarcoma 180 tumor-bearing control mice in vivo. We found that the compound significantly suppressed phosphorylation of extracellular signal-regulated kinase (pERK) and activated c-jun-N-terminal kinase (JNK) and protein kinase C (PKC)-alpha following 4 h-treatment. These findings indicate that 2-hyim-DMSQ-S33 exerts antitumor activities by regulating pERK, JNK and PKC-alpha.
Kim
S H
SH
Department of Oncology, Graduate School of East-West Medical Science, KyungHee University, 1 Seochun-ri, Kiheung-eup, 449-701, Yongin, South Korea. sungkim7@khu.ac.kr
Kang
I C
IC
Yoon
T J
TJ
Park
Y M
YM
Kang
K S
KS
Song
G Y
GY
Ahn
B Z
BZ
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011493:Protein Kinase C / Q000378:metabolism
C437885:2-(1-hydroxyiminohexyl)-5,8-dimethoxy-1,4-naphthoquinone-S33; D000972:Antineoplastic Agents, Phytogenic; D009285:Naphthoquinones; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases