Antitumor activities of a newly synthesized shikonin derivative, 2-hyim-DMNQ-S-33

Cancer Lett. 2001 Oct 30;172(2):171-5. doi: 10.1016/s0304-3835(01)00665-6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Division / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mitogen-Activated Protein Kinases / metabolism
  • Naphthoquinones / pharmacology
  • Neoplasms, Experimental / drug therapy
  • Protein Kinase C / metabolism

Substances

  • 2-(1-hydroxyiminohexyl)-5,8-dimethoxy-1,4-naphthoquinone-S33
  • Antineoplastic Agents, Phytogenic
  • Naphthoquinones
  • Protein Kinase C
  • Mitogen-Activated Protein Kinases