Mangrove dolabrane-type of diterpenes tagalsins suppresses tumor growth via ROS-mediated apoptosis and ATM/ATR-Chk1/Chk2-regulated cell cycle arrest

• Verfasst von: Neumann, Jennifer [VerfasserIn]
• Verfasst von: Witzens-Harig, Mathias [VerfasserIn]
• Verfasst von: Krammer, Peter H. [VerfasserIn]
• Titel: Mangrove dolabrane-type of diterpenes tagalsins suppresses tumor growth via ROS-mediated apoptosis and ATM/ATR-Chk1/Chk2-regulated cell cycle arrest
• Verf.angabe: Jennifer Neumann, Yi Yang, Rebecca Köhler, Marco Giaisi, Mathias Witzens‐Harig, Dong Liu, Peter H. Krammer, Wenhan Lin and Min Li‐Weber
• E-Jahr: 2015
• Jahr: 09 June 2015
• Umfang: 10 S.
• Fussnoten: Gesehen am 17.08.2020
• Titel Quelle: Enthalten in: International journal of cancer
• Ort Quelle: Bognor Regis : Wiley-Liss, 1966
• Jahr Quelle: 2015
• Band/Heft Quelle: 137(2015), 11, Seite 2739-2748
• ISSN Quelle: 1097-0215
• DOI: doi:10.1002/ijc.29629
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: apoptosis
• Sach-SW: ATM
• Sach-SW: ATR
• Sach-SW: cancer
• Sach-SW: Cdc25A
• Sach-SW: Chk1
• Sach-SW: Chk2
• K10plus-PPN: 1727174089

Abstract

Natural compounds are an important source for drug development. With an increasing cancer rate worldwide there is an urgent quest for new anti-cancer drugs. In this study, we show that a group of dolabrane-type of diterpenes, collectively named tagalsins, isolated from the Chinese mangrove genus Ceriops has potent cytotoxicity on a panel of hematologic cancer cells. Investigation of the molecular mechanisms by which tagalsins kill malignant cells revealed that it induces a ROS-mediated damage of DNA. This event leads to apoptosis induction and blockage of cell cycle progression at S-G2 phase via activation of the ATM/ATR—Chk1/Chk2 check point pathway. We further show that tagalsins suppress growth of human T-cell leukemia xenografts in vivo. Tagalsins show only minor toxicity on healthy cells and are well tolerated by mice. Our study shows a therapeutic potential of tagalsins for the treatment of hematologic malignancies and a new source of anticancer drugs.