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

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 Cer...

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Hauptverfasser: Neumann, Jennifer (Verfasst von) , Witzens-Harig, Mathias (Verfasst von) , Krammer, Peter H. (Verfasst von)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 09 June 2015
In: International journal of cancer
Year: 2015, Jahrgang: 137, Heft: 11, Pages: 2739-2748
ISSN:1097-0215
DOI:10.1002/ijc.29629
Online-Zugang:Verlag, Volltext: https://doi.org/10.1002/ijc.29629
Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.29629
Volltext
Verfasserangaben:Jennifer Neumann, Yi Yang, Rebecca Köhler, Marco Giaisi, Mathias Witzens‐Harig, Dong Liu, Peter H. Krammer, Wenhan Lin and Min Li‐Weber
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 17.08.2020
Beschreibung:Online Resource
ISSN:1097-0215
DOI:10.1002/ijc.29629

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