NBRI16716A, a new antitumor compound against human prostate cancer cells, produced by Perisporiopsis melioloides Mer-f16716.
Prostate stroma can regulate the growth and metastasis of prostate cancer through the tumor-stromal cell interactions. Thus, small molecules that modulate the tumor-stromal cell interactions will have a chance to become new antitumor drugs. In the course of our screening of the modulators, we isolated three new natural compounds, NBRI16716A (1), NBRI16716B (2) and NBRI16716C (3), from the fermentation broth of Perisporiopsis melioloides Mer-f16716, although compound 2 was already reported as a chemical degradation product of isotriornicin. Compounds 1 and 2 inhibited the growth of human prostate cancer DU-145 cells in the coculture with human prostate stromal cells (PrSCs) more strongly than that of DU-145 cells alone. Furthermore, both compounds showed antitumor effect against xenograft models of DU-145 cells and PrSCs in vivo.
Kawada
Manabu
M
Numazu Bio-Medical Research Institute, Microbial Chemistry Research Center, Numazu-shi, Shizuoka, Japan. kawadam@bikaken.or.jp
Someno
Tetsuya
T
Inoue
Hiroyuki
H
Ohba
Shun-ichi
S
Masuda
Tohru
T
Kato
Taira
T
Ikeda
Daishiro
D
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000302:isolation & purification* / Q000627:therapeutic use / Q000633:toxicity; D001203:Ascomycota / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011719:Pyrazines / Q000302:isolation & purification* / Q000627:therapeutic use / Q000633:toxicity
D000903:Antibiotics, Antineoplastic; C550745:NBRI16716A; D011719:Pyrazines