Tatsuo Yagura

Major research fields

TatsuoYaguraMolecular Cell Biology, Molecular Cancer Therapeutics

In the past decade, understanding the pathogenesis of leukemia, the development of new targeted therapy drugs, and the refinement of protocols for their chemotherapy have improved survival in leukemia, especially in acute lymphoblastic leukemia. However, many patients relapse and develop drug resistance. Bismuth is an unusual element in term of its low toxicity and non-carcinogenic nature in spite of its heavy metal status. Bismuth compounds have been used in medicine and veterinary practice. Recently, the physiological aspect of bismuth chemistry has received considerable attention, and much effort has been devoted to the synthesis of different types of bismuth compounds. We have identified several classes of heterocyclic organobismuth compounds as a novel apoptosis inducer. Furthermore, we found that these organobismuth compounds have potent antiproliferative activity against human leukemic cells and inhibit microtubule polymerization. These biological activities of organobismuth compounds have been shown to differ depending on the compound structure, but the detailed molecular basis of the mechanism of organobismuth compound bioactivity is still unclear. Therefore, in an effort to develop bismuth-based organic compounds with enhanced/selective anticancer activities, we attempt to synthesize novel organometallic compounds and examine their biological activity using techniques of molecular cell biology.

Major relevant publications

  1. Onishi,K., Douke,M., Nakamura,T., Ochiai,Y., Kakusawa,N., Yasuike,S., Kurita,J., Yamamoto,C., Kawahata,M., Yamaguchi,K., and Yagura,T. A novel organobismuth compound, 1-[(2-di-p-tolylbismuthanophenyl)diazenyl] pyrrolidine, induces apoptosis in the human acute promyelocytic leukemia cell line NB4 via reactive oxygen species. J.Inorganic Biochem., 117, 77-84 (2012)
  2. Iuchi,K., Akagi,K., and Yagura,T. Heterocyclic organobismuth (III) compound target stubulin to induce G2/M arrest in HeLa cells. J. Pharmacol. Sci., 109,573-582 (2009)
  3. Iuchi,K., Hatano,Y., and Yagura,T. Heterocyclic organobismuth (III) induces poptosis of human promyelocytic leukemic cells through activation of caspases and mitochondrial perturbation. Biochem. Pharmacol. 76, 974-9896 (2008)
  4. Kotani,T., Nagai,D., Asahi,K., Suzuki,H., Yamao,F., Kataoka,N., and Yagura,T. Antibacterial properties of some cyclic organobismuth (III) compounds. Antimicro. Agents Chemother. 49, 2729-2734 (2005)
  5. Yamada,J., Sugimoto,Y., Ujikawa,M., Goko,H., and Yagura,T. Hyperleptinemia elicited by the 5-HT precursor, 5-hydroxytryptophan in mice: involvement of insulin. Life Sci., 73, 2335-2344 (2003)

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