NBRI17671, a new antitumor compound, produced by Acremonium sp. CR17671.
The interaction between the receptor for advanced glycation end-product (RAGE) and amphoterin has an important role in tumor growth and metastasis. Because the abrogation of the interaction results in the inhibition of the tumor growth and metastasis, we designed a screening system for an inhibitor of the interaction between RAGE and amphoterin. In the course of our screening of the inhibitor, we isolated a novel natural compound NBRI17671 (1) from the fermentation broth of Acremonium sp. CR17671. We also modified 1 into a more active NBRI17671al (2). Although 1 at 50 g ml(-1) weakly inhibited binding of various cells to amphoterin, 2 at 50 g ml(-1) inhibited it by >50% of control. Compound 2 effectively inhibited the tumor growth of glioma and lung tumor xenografts in mice at 25 mg kg(-1). Furthermore, 2 was found to downregulate mitogen-activated protein kinase (MAPK) activity in the tumor cells.
Kawada
Manabu
M
Numazu Bio-Medical Research Institute, Microbial Chemistry Research Center, Shizuoka, Japan. kawadam@bikaken.or.jp
Usami
Ihomi
I
Someno
Tetsuya
T
Watanabe
Takumi
T
Abe
Hikaru
H
Inoue
Hiroyuki
H
Ohba
Shun-ichi
S
Masuda
Tohru
T
Tabata
Yuji
Y
Yamaguchi
Sho-ichi
S
Ikeda
Daishiro
D
D000164:Acremonium / Q000378:metabolism*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005910:Glioma / Q000188:drug therapy; D024243:HMGB1 Protein / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors; D013764:Tetrahydronaphthalenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D024243:HMGB1 Protein; C550110:NBRI17671; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D013764:Tetrahydronaphthalenes; D020928:Mitogen-Activated Protein Kinases