Kigamicin D, a novel anticancer agent based on a new anti-austerity strategy targeting cancer cells' tolerance to nutrient starvation
| العنوان: | Kigamicin D, a novel anticancer agent based on a new anti-austerity strategy targeting cancer cells' tolerance to nutrient starvation |
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| المؤلفون: | Setsuko Kunimoto, Jie Lu, Yohko Yamazaki, Hiroyasu Esumi, Michio Kaminishi |
| المصدر: | Cancer Science. 95:547-552 |
| بيانات النشر: | Wiley, 2004. |
| سنة النشر: | 2004 |
| مصطلحات موضوعية: | Cancer Research, Angiogenesis, Antineoplastic Agents, Protein Serine-Threonine Kinases, Biology, Mice, Necrosis, Cell Line, Tumor, Proto-Oncogene Proteins, medicine, Animals, Humans, Phosphorylation, Cytotoxicity, Oxazoles, Protein kinase B, Starvation, Mice, Inbred BALB C, Cancer, Neoplasms, Experimental, General Medicine, medicine.disease, Culture Media, Oncology, Biochemistry, Doxorubicin, Cell culture, Cancer cell, Cancer research, Experimental pathology, Female, medicine.symptom, Proto-Oncogene Proteins c-akt |
| الوصف: | Both tolerance to nutrient starvation and angiogenesis are essential 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 nutrient-deprived media. After screening over 2000 culture media of actinomycetes, we identified a new compound, kigamicin D (C(48)H(59)NO(19)), which shows preferential cytotoxicity to cancer cells under nutrient-deprived conditions, but hardly any cytotoxicity under nutrient-rich conditions. Both subcutaneous and oral administration 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 suggest that kigamicin D be a candidate for implementing our novel concept, anti-austerity, which may serve as a new strategy for cancer therapy. |
| تدمد: | 1349-7006 1347-9032 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5ecd52289b86fb5a23093c259cc37a96 https://doi.org/10.1111/j.1349-7006.2004.tb03247.x |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....5ecd52289b86fb5a23093c259cc37a96 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13497006 13479032 |
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