Yoshio Koide

The structure of neocarzinostatin chromophore possessing a novel bicyclo-[7,3,0]dodecadiyne system

Abstract The structure of the chromophore of an antitumor antibiotic neocarzinostatin has been elucidated as a bicycro[7,3,0]dodecadiyne system having naphthalenecarboxylic acid, aminosugar and ethylene carbonate units.

Expression of stanniocalcin in zona glomerulosa and medulla of normal human adrenal glands, and some adrenal tumors and cell lines

Stanniocalcin (STC) is a calcium (Ca)‐regulating hormone that was originally discovered in the fish Stannius body, which is a unique endocrine organ. Hypercalcemia increases STC secretion, which inhibits Ca uptake by the gills and normalizes serum Ca level. In this study we investigated the STC expression in human normal and abnormal adrenal cells. Immunohistochemistry using monoclonal antibody against STC revealed specific staining in zona glomerulosa and medulla of normal human adrenal glands. STC was also detected in human adrenal tumors, such as pheochromocytoma, differentiated neuroblastoma, and aldosterone‐producing adenoma, and cultured adrenal tumor cells (rat pheochromocytoma PC‐12 cells and human neuroblastoma NB‐1 cells). However, undifferentiated human adrenal neuroblastoma was negative for STC staining. Reverse transcription polymerase chain reaction demonstrated STC mRNA expression in cultured PC‐12 cells and NB‐1 cells. Following several studies indicating that zona glomerulosa cells of adrenal glands express neuroendocrine properties, STC expression in normal and abnormal adrenal cells provides additional evidence to support the neuroendocrine differentiation of these cells. In conclusion, STC may be useful as a new cell marker of adrenal glands under physiological and pathological conditions.

Neocarzinostatin Chromophore: Structure and Mechanism of DNA Cleavage

Neocarzinostatin (NCS) is a member of a family of chromoprotein antitumor antibiotics. It consists of two noncovalently bound components, a labile chromophore component (NCS-chrom) with biological activities such as DNA cleavage and a protein component that stabilizes NCS-chrom. NCSchrom was the first of the enediyne antibiotics to be isolated and characterized. The chemical structure has been elucidated: a novel epoxybicyclo [7,3,01 dodecadienediyne system, an interconnecting highly unsaturated 12-member carbon ring subunit, bearing subunits 2-hydroxy-5-methyl-7-methoxyl1-naphthoate, 2,6-dideoxy-2-methylamino-galactose, and ethylene carbonate. The mechanism for the activation of NCS-chrom highlights one of the crucial roles of the thiol in the mechanism of action of NCS. Nucleophilic attack by a thiol results in a Bergman-type electronic rearrangement to form a biradical species that cleaves DNA by abstracting hydrogen atoms from the deoxyribose sugar. Moreover, another pathway for the thiol-independent mechanism of action of NCS-chrom has been proposed. In this mechanism, the spirolactone cumulene is stereoselectively generated via an intramolecular Michael addition at C-12 by the enolate anion of naphthoate of NCS-chrom, resulting in the formation of the biradical.