title: Cardenolide glycosides from the seeds of Digitalis purpurea exhibit carcinoma-specific cytotoxicity toward renal adenocarcinoma and hepatocellular carcinoma cells.
abstract: Four cardenolide glycosides, glucodigifucoside (2), 3'-O-acetylglucoevatromonoside (9), digitoxigenin 3-O-β-D-glucopyranosyl-(1 → 4)-β-D-glucopyranosyl-(1 → 4)-3-O-acetyl-β-D-digitoxopyranoside (11), and purpureaglycoside A (12), isolated from the seeds of Digitalis purpurea, exhibited potent cytotoxicity against human renal adenocarcinoma cell line ACHN. These compounds exhibited significantly lower IC50 values against ACHN than that against normal human renal proximal tubule-derived cell line HK-2. In particular, 2 exhibited the most potent and carcinoma-specific cytotoxicity, with a sixfold lower IC50 value against ACHN than that against HK-2. Measurement of cyclin-dependent kinase inhibitor levels revealed that upregulation of p21/Cip1 expression was involved in the carcinoma-specific cytotoxicity of 2. Further, compound 2 also exhibited the carcinoma-specific cytotoxicity toward hepatocellular carcinoma cell line.
authors.affiliation: a Department of Hygiene and Health Sciences , Tokyo University of Pharmacy and Life Sciences, School of Pharmacy , Tokyo , Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Fujino
authors.forename: Minpei
authors.initials: M
authors.lastname: Kuroda
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Matsuo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kubo
authors.forename: Chikako
authors.initials: C
authors.lastname: Tamura
authors.forename: Nami
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Mimaki
authors.forename: Makio
authors.initials: M
authors.lastname: Hayakawa
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002298:Cardenolides / Q000737:chemistry*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004070:Digitalis / Q000737:chemistry*; D006027:Glycosides / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology; D012639:Seeds / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002298:Cardenolides; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006027:Glycosides; D016159:Tumor Suppressor Protein p53
keywords: CDK inhibitor; adenocarcinoma; carcinoma-specific cytotoxicity; cardenolide glycoside; hepatocellular carcinoma