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Nanoliposomal ceramide prevents in vivo growth of hepatocellular carcinoma.
Gut. 2011 May; 60(5):695-701.Gut

Abstract

BACKGROUND AND OBJECTIVES

Hepatocellular carcinoma (HCC) affects an increasing number of people worldwide. The poor survival rate of patients with HCC is manifested by an aggressive and metastatic phenotype, as well as a poor response to common therapeutic strategies. The purpose of this study was to evaluate the efficacy of nanoliposomal C6-ceramide as an antineoplastic agent in an in vivo model of human HCC.

METHODS

The growth-arresting and pro-apoptotic properties of nanoliposomal C6-ceramide were first evaluated in vitro in human SK-HEP-1 cells by assessing cellular viability, caspase 3/7 activity, annexin-V expression, DNA fragmentation, cell cycle distribution and AKT phosphorylation. SK-HEP-1 cells were then engrafted subcutaneously into athymic nude mice and nanoliposomal C6-ceramide was administered by tail vein injection. Tumour size was monitored over time, followed by excision of tumours to evaluate tumour vascularisation, proliferation, apoptosis and cellular signalling.

RESULTS

Nanoliposomal C6-ceramide, but not ghost (no ceramide) nanoliposomes, induced apoptotic cell death of SK-HEP-1 cells in vitro, concomitant with an accumulation of cells in the G₂ phase of the cell cycle and decreased phosphorylation of AKT. Systemic administration of nanoliposomal C6-ceramide to mice engrafted with SK-HEP-1 tumours reduced tumour vascularisation and proliferation, induced tumour cell apoptosis, decreased phosphorylation of AKT and ultimately blocked tumour growth.

CONCLUSIONS

These studies show that nanoliposomal ceramide is an efficacious antineoplastic agent for the treatment of in vitro and in vivo models of human HCC.

Authors+Show Affiliations

Departments of Pharmacology and of Cellular and Molecular Physiology, Hershey, PA 17033-0858, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21193455

Citation

Tagaram, Hephzibah Rani S., et al. "Nanoliposomal Ceramide Prevents in Vivo Growth of Hepatocellular Carcinoma." Gut, vol. 60, no. 5, 2011, pp. 695-701.
Tagaram HR, Divittore NA, Barth BM, et al. Nanoliposomal ceramide prevents in vivo growth of hepatocellular carcinoma. Gut. 2011;60(5):695-701.
Tagaram, H. R., Divittore, N. A., Barth, B. M., Kaiser, J. M., Avella, D., Kimchi, E. T., Jiang, Y., Isom, H. C., Kester, M., & Staveley-O'Carroll, K. F. (2011). Nanoliposomal ceramide prevents in vivo growth of hepatocellular carcinoma. Gut, 60(5), 695-701. https://doi.org/10.1136/gut.2010.216671
Tagaram HR, et al. Nanoliposomal Ceramide Prevents in Vivo Growth of Hepatocellular Carcinoma. Gut. 2011;60(5):695-701. PubMed PMID: 21193455.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nanoliposomal ceramide prevents in vivo growth of hepatocellular carcinoma. AU - Tagaram,Hephzibah Rani S, AU - Divittore,Nicole A, AU - Barth,Brian M, AU - Kaiser,James M, AU - Avella,Diego, AU - Kimchi,Eric T, AU - Jiang,Yixing, AU - Isom,Harriet C, AU - Kester,Mark, AU - Staveley-O'Carroll,Kevin F, Y1 - 2010/12/30/ PY - 2011/1/4/entrez PY - 2011/1/5/pubmed PY - 2011/7/23/medline SP - 695 EP - 701 JF - Gut JO - Gut VL - 60 IS - 5 N2 - BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) affects an increasing number of people worldwide. The poor survival rate of patients with HCC is manifested by an aggressive and metastatic phenotype, as well as a poor response to common therapeutic strategies. The purpose of this study was to evaluate the efficacy of nanoliposomal C6-ceramide as an antineoplastic agent in an in vivo model of human HCC. METHODS: The growth-arresting and pro-apoptotic properties of nanoliposomal C6-ceramide were first evaluated in vitro in human SK-HEP-1 cells by assessing cellular viability, caspase 3/7 activity, annexin-V expression, DNA fragmentation, cell cycle distribution and AKT phosphorylation. SK-HEP-1 cells were then engrafted subcutaneously into athymic nude mice and nanoliposomal C6-ceramide was administered by tail vein injection. Tumour size was monitored over time, followed by excision of tumours to evaluate tumour vascularisation, proliferation, apoptosis and cellular signalling. RESULTS: Nanoliposomal C6-ceramide, but not ghost (no ceramide) nanoliposomes, induced apoptotic cell death of SK-HEP-1 cells in vitro, concomitant with an accumulation of cells in the G₂ phase of the cell cycle and decreased phosphorylation of AKT. Systemic administration of nanoliposomal C6-ceramide to mice engrafted with SK-HEP-1 tumours reduced tumour vascularisation and proliferation, induced tumour cell apoptosis, decreased phosphorylation of AKT and ultimately blocked tumour growth. CONCLUSIONS: These studies show that nanoliposomal ceramide is an efficacious antineoplastic agent for the treatment of in vitro and in vivo models of human HCC. SN - 1468-3288 UR - https://www.unboundmedicine.com/medline/citation/21193455/Nanoliposomal_ceramide_prevents_in_vivo_growth_of_hepatocellular_carcinoma_ L2 - https://gut.bmj.com/lookup/pmidlookup?view=long&pmid=21193455 DB - PRIME DP - Unbound Medicine ER -