Synergistic combination therapy with nanoliposomal C6-ceramide and vinblastine is associated with autophagy dysfunction in hepatocarcinoma and colorectal cancer models

Highlights • C6-ceramide nanoliposome and vinblastine combination treatment resulted in blockade of autophagy maturation/degradation. • Combination treatment synergistically enhanced cytotoxicity and apoptotic cell death in vitro. • Combination treatment resulted in synergistic tumor growth suppress...

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Bibliographic Details
Published in:Cancer letters 2013-09, Vol.337 (2), p.254-265
Main Authors: Adiseshaiah, Pavan P, Clogston, Jeffrey D, McLeland, Christopher B, Rodriguez, Jamie, Potter, Timothy M, Neun, Barry W, Skoczen, Sarah L, Shanmugavelandy, Sriram S, Kester, Mark, Stern, Stephan T, McNeil, Scott E
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - metabolism
Animals
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Apoptosis
Apoptosis - drug effects
Apoptosis Regulatory Proteins - genetics
Apoptosis Regulatory Proteins - metabolism
Autophagy
Autophagy - drug effects
Beclin-1
Cancer therapies
Carcinoma, Hepatocellular - drug therapy
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - pathology
Caspase 3 - metabolism
Caspase 7 - metabolism
Cell Survival - drug effects
Ceramide
Ceramides - administration & dosage
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
Combination therapy
Cytotoxicity
Dose-Response Relationship, Drug
Drug Synergism
Genes
Hematology, Oncology and Palliative Medicine
Hep G2 Cells
Humans
Injections, Intravenous
Liposomes
Liver cancer
Liver Neoplasms - drug therapy
Liver Neoplasms - genetics
Liver Neoplasms - pathology
Membrane Proteins - genetics
Membrane Proteins - metabolism
Metabolism
Mice
Mice, Nude
Nanoparticles
Proteins
RNA Interference
Rodents
Sequestosome-1 Protein
Studies
Transfection
Tumor Burden - drug effects
Tumorigenesis
Tumors
Vinblastine - administration & dosage
Xenograft Model Antitumor Assays
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Summary:Highlights • C6-ceramide nanoliposome and vinblastine combination treatment resulted in blockade of autophagy maturation/degradation. • Combination treatment synergistically enhanced cytotoxicity and apoptotic cell death in vitro. • Combination treatment resulted in synergistic tumor growth suppression and TUNEL staining, without increasing toxicity. • In summary, data support a synergistic antitumor activity of the combination treatment, mediated by an autophagy mechanism.
ISSN:0304-3835
1872-7980
1872-7980
DOI:10.1016/j.canlet.2013.04.034