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About the Authors:
Xiaohua Song
Affiliation: Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada
Ana Lopez-Campistrous
Affiliation: Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada
Lucy Sun
Affiliation: Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada
Nancy A. Dower
Affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
Noemi Kedei
Affiliation: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Jing Yang
Affiliation: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Jessica S. Kelsey
Affiliation: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Nancy E. Lewin
Affiliation: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Tim E. Esch
Affiliation: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Peter M. Blumberg
Affiliation: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
James C. Stone
* E-mail: [email protected]
Affiliation: Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada
Introduction
Diacylglycerol (DAG) is a potent second messenger that is generated in cells in response to membrane receptor stimulation of phospholipid metabolism. DAG and DAG analogues such as PMA (phorbol 12-myristate 13-acetate) bind conventional and novel forms of protein kinase C (PKC) through a conserved domain called C1. This process contributes to PKC membrane localization and enzyme activation. Prolonged exposure to DAG analogues can also negatively impact PKC activity through induced enzyme degradation. Some DAG analogues, such as PMA, are potent tumor promoters. Other DAG analogues, such as prostratin and bryostatin 1, are non-tumor promoters or may indeed inhibit tumor promotion. Medicinal DAG analogues such as bryostatin 1 exert a variety of anti-cancer cell and immune modulatory effects. Based on encouraging preclinical data, bryostatin 1 has been the subject of extensive cancer clinical trials (http://clinicaltrials.gov/ct2/results?term=bryostatin).
Another medicinal DAG analogue of clinical interest is ingenol-3-angelate (I3A). I3A was...