PUBLICATION
Marine guanidine alkaloids crambescidins inhibit tumor growth and activate intrinsic apoptotic signaling inducing tumor regression in a colorectal carcinoma zebrafish xenograft model
- Authors
- Roel, M., Rubiolo, J.A., Guerra-Varela, J., Silva, S.B., Thomas, O.P., Cabezas-Sainz, P., Sánchez, L., López, R., Botana, L.M.
- ID
- ZDB-PUB-161110-12
- Date
- 2016
- Source
- Oncotarget 7(50): 83071-83087 (Journal)
- Registered Authors
- Keywords
- apoptosis, cancer treatment, cell cycle inhibition, crambescidins, zebrafish xenograft model
- MeSH Terms
-
- Alkaloids/pharmacology*
- Animals
- Antineoplastic Agents/pharmacology*
- Apoptosis/drug effects*
- Caspase 3/metabolism
- Cell Adhesion/drug effects
- Cell Cycle Proteins/metabolism
- Cell Proliferation/drug effects*
- Cell Survival/drug effects
- Colorectal Neoplasms/drug therapy*
- Colorectal Neoplasms/metabolism
- Colorectal Neoplasms/pathology
- Cytoskeleton/drug effects
- Cytoskeleton/metabolism
- Cytoskeleton/pathology
- Dose-Response Relationship, Drug
- G1 Phase Cell Cycle Checkpoints/drug effects
- Guanidine/analogs & derivatives*
- Guanidine/pharmacology
- HT29 Cells
- Hep G2 Cells
- Humans
- Inhibitory Concentration 50
- MCF-7 Cells
- Membrane Potential, Mitochondrial/drug effects
- Signal Transduction/drug effects*
- Spiro Compounds/pharmacology*
- Time Factors
- Tumor Burden/drug effects
- Xenograft Model Antitumor Assays
- Zebrafish
- PubMed
- 27825113 Full text @ Oncotarget
Citation
Roel, M., Rubiolo, J.A., Guerra-Varela, J., Silva, S.B., Thomas, O.P., Cabezas-Sainz, P., Sánchez, L., López, R., Botana, L.M. (2016) Marine guanidine alkaloids crambescidins inhibit tumor growth and activate intrinsic apoptotic signaling inducing tumor regression in a colorectal carcinoma zebrafish xenograft model. Oncotarget. 7(50):83071-83087.
Abstract
The marine environment constitutes an extraordinary resource for the discovery of new therapeutic agents. In the present manuscript we studied the effect of 3 different sponge derived guanidine alkaloids, crambescidine-816, -830, and -800. We show that these compounds strongly inhibit tumor cell proliferation by down-regulating cyclin-dependent kinases 2/6 and cyclins D/A expression while up-regulating the cell cyclin-dependent kinase inhibitors -2A, -2D and -1A. We also show that these guanidine compounds disrupt tumor cell adhesion and cytoskeletal integrity promoting the activation of the intrinsic apoptotic signaling, resulting in loss of mitochondrial membrane potential and concomitant caspase-3 cleavage and activation. The crambescidin 816 anti-tumor effect was fnally assayed in a zebrafish xenotransplantation model confirming its potent antitumor activity against colorectal carcinoma in vivo.Considering these results crambescidins could represent promising natural anticancer agents and therapeutic tools.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping