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Mangrove dolabrane‐type of diterpenes tagalsins suppresses tumor growth via ROS ‐mediated apoptosis and ATM/ATR–C hk1/Chk2‐regulated cell cycle arrest
Author(s) -
Neumann Jennifer,
Yang Yi,
Köhler Rebecca,
Giaisi Marco,
WitzensHarig Mathias,
Liu Dong,
Krammer Peter H.,
Lin Wenhan,
LiWeber Min
Publication year - 2015
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29629
Subject(s) - cell cycle checkpoint , apoptosis , cell cycle , cytotoxicity , dna damage , cancer research , biology , cancer cell , leukemia , in vivo , cell growth , chemistry , cancer , pharmacology , in vitro , biochemistry , immunology , dna , genetics
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.