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. 2005 Aug 19;95(6):547–552. doi: 10.1111/j.1349-7006.2004.tb03247.x

Kigamicin D, a novel anticancer agent based on a new anti‐austerity strategy targeting cancer cells' tolerance to nutrient starvation

Jie Lu 1,3, Setsuko Kunimoto 2, Yohko Yamazaki 2, Michio Kaminishi 3, Hiroyasu Esumi 1,✉
PMCID: PMC11158080  PMID: 15182438

Abstract

Both tolerance to nutrient starvation and angiogenesis are esse tial for cancer progression because of the insufficient supply of nutrients to tumor tissue. Since chronic nutrient starvation seldom occurs in normal tissue, cancer's tolerance to nutrient starvation should provide a novel target for cancer therapy. In this study, we propose an anti‐austerity strategy to exploit the ability of agents to eliminate cancer cells' tolerance to nutrient starvation. We established a simple screening method for agents that inhibit cancer cell viability preferentially during nutrient starvation, using PANC‐1 cell line cultured in nutrient‐rich and nutrien deprived media. After screening over 2000 culture media of act nomycetes, we identified a new compound, kigamicin (C48H59NO19), which shows preferential cytotoxicity to cancer ceels under nutrient‐deprived conditions, but hardly any cytotoxici under nutrient‐rich conditions. Both subcutaneous and oral a ministration of kigamicin D strongly suppressed the tumor growth of several tested pancreatic cancer cell lines in nude mice Moreover, kigamicin D was observed to block the activation of Akt induced by nutrient starvation. Therefore, our results sugge that kigamicin D be a candidate for implementing our novel concept, anti‐austerity, which may serve as a new strategy for cancer therapy.

Abbreviations:

DMEM

Dulbecco's modified Eagle's medium

IHC

immunohistochemistry

PKB

protein kinase B

PI‐3K

phosphatidylinositol 3‐OH‐kinase

NDM

nutrient‐deprived medium

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