New atpenins, NBRI23477 A and B, inhibit the growth of human prostate cancer cells

Abstract

The growth and metastasis of prostate cancer are regulated by prostate stroma through the tumor-stromal cell interactions. Small molecules that modulate the tumor-stromal cell interactions will be new anticancer drugs. In the course of our screening of the modulators, we isolated two new atpenins, NBRI23477 A (4) and B (5), from the fermentation broth of Penicillium atramentosum PF1420. Compounds 4 and 5 as well as atpenin A4 (1), A5 (2) and B (3) inhibited the growth of human prostate cancer DU-145 cells in the coculture with human prostate stromal cells more strongly than that of DU-145 cells alone.

NBRI16716A, a new antitumor compound against human prostate cancer cells, produced by Perisporiopsis melioloides Mer-f16716

“…8 These compounds were also re-discovered as modulators of tumorstromal cell interactions by our screening program. 5,6 In this paper, we have reported new natural compounds from fungal metabolite. Although the study of the precise mechanism is going on, 1 and 2 are considered to modulate the tumor-stromal cell interactions similar to other compounds reported previously.…”

“…Although the study of the precise mechanism is going on, 1 and 2 are considered to modulate the tumor-stromal cell interactions similar to other compounds reported previously. [6][7][8] As we obtained a new compound with potency of antitumor effect in vivo, we thought that our screening concept and program would be beneficial for the innovation of new antitumor drugs. …”

“…DU-145 cells (8Â10 6 ) were trypsinized and resuspended with or without PrSCs (8Â10 6 ) in 0.3 ml of 10% fetal bovine serum/DMEM and then combined with 0.5 ml of growth factor-reduced Matrigel (BD Biosciences, San Jose, CA, USA). A total of 100 ml of the cell suspension (1Â10 6 cells) was injected subcutaneously in the left lateral flank of mice.…”

“…3,5 Using the assay method as a screening system for antitumor compounds, we have been finding several compounds that exert antitumor effects through modulation of the tumor-stromal cell interactions. 6,7 We have recently reported that leucinostatin A, a fungus natural compound, showed antitumor effect against xenograft models of human prostate cancer cells in vivo through the downregulation of insulin-like growth factor-I secretion from PrSCs. 8 By continuing the screening system, we have found new natural compounds from a fungal strain Perisporiopsis melioloides Mer-f16716.…”

Synthesis and Structure–Activity Relationship Study of NBRI16716B, an Antitumor Natural Product

“…Natural products were used as the major source for our screening platform; the structural variety of natural products is expected to bait a diverse array of counterpart proteins. In fact, several natural products exhibit the desired activity and selectivity, including phthoxazolin A, 10) NBRI23477 A and B, 11) leucinostatins, 12) and intervenolin. 13,14) Two of NBRI16716s 15) (Fig.…”