13-Oxyingenol dodecanoate, a cytotoxic ingenol derivative, induces mitochondrial apoptosis and caspase-dependent Akt decrease in K562 cells.

Abstract

13-Oxyingenol dodecanoate (13OD) is an ingenol derivative prepared from Chinese traditional medicine Euphorbia kansui without any report about its bioactivity. The present study demonstrated for the first time that 13OD displayed potent cytotoxicity against chronic myeloid leukemia K562 cells in vitro. 13OD inhibited proliferation, induced G2/M phase arrest, and exhibited potent apoptotic activity in K562 cells. In K562 cells, 13OD disrupted the mitochondrial membrane potential and induced high level of ROS, which played an indispensable role in 13OD-induced apoptosis. Further investigations on the molecular mechanisms revealed that total Akt protein level was decreased in a caspase-dependent way after treatment with 13OD; in addition, ERK was activated by 13OD, and this activation played a protective role in 13OD stimulation. Altogether, these results revealed that the cytotoxic ingenol derivative 13OD induced apoptosis with novel mechanisms for the proapoptotic function in cancer cells, and suggested that 13OD may serve as a lead template for rational drug design and for future anticancer agent development.

• Authors: Ming Liu, Weiyi Zhang, Genzhu Wang, Xiaoping Song, Xingzeng Zhao, Xiangyun Wang, Xin Qi, Jing Li
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 37 Issue 5 Pg. 6227-38 (May 2016) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 26615422 (Publication Type: Journal Article)

Chemical References

• 13-oxyingenol
• Diterpenes
• Proto-Oncogene Proteins c-akt
• Caspases

Topics

• Apoptosis (drug effects)
• Caspases (genetics)
• Cell Proliferation (drug effects)
• Diterpenes (administration & dosage)
• G2 Phase Cell Cycle Checkpoints (drug effects)
• Humans
• K562 Cells
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, genetics, pathology)
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects)
• Proto-Oncogene Proteins c-akt (genetics)
• Signal Transduction (drug effects)