Mangrove dolabrane‐type of diterpenes tagalsins suppresses tumor growth viaROS‐mediated apoptosis and ATM/ATR–Chk1/Chk2‐regulated cell cycle arrest
Mangrove dolabrane‐type of diterpenes tagalsins suppresses tumor growth viaROS‐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 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.
- Peking University China (People's Republic of)
- Peking University China (People's Republic of)
- Peking University China (People's Republic of)
- Univerity of Heidelberg Germany
- Peking University China (People's Republic of)
G2 Phase, Leukemia, T-Cell, Tumor Suppressor Proteins, Antineoplastic Agents, Apoptosis, Ataxia Telangiectasia Mutated Proteins, Cell Cycle Checkpoints, S Phase, Checkpoint Kinase 2, Jurkat Cells, Mice, Cell Line, Tumor, Checkpoint Kinase 1, Cancer Therapy, Animals, Humans, Rhizophoraceae, Diterpenes, Reactive Oxygen Species, Protein Kinases, DNA Damage
G2 Phase, Leukemia, T-Cell, Tumor Suppressor Proteins, Antineoplastic Agents, Apoptosis, Ataxia Telangiectasia Mutated Proteins, Cell Cycle Checkpoints, S Phase, Checkpoint Kinase 2, Jurkat Cells, Mice, Cell Line, Tumor, Checkpoint Kinase 1, Cancer Therapy, Animals, Humans, Rhizophoraceae, Diterpenes, Reactive Oxygen Species, Protein Kinases, DNA Damage
15 Research products, page 1 of 2
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