Antitumor activity of tripterine via cell-penetrating peptide-coated nanostructured lipid carriers in a prostate cancer model.

Abstract

BACKGROUND:

The purpose of this study was to evaluate the antitumor effect of cell-penetrating peptide-coated tripterine-loaded nanostructured lipid carriers (CT-NLC) on prostate tumor cells in vitro and in vivo.

METHODS:

CT-NLC were developed to improve the hydrophilicity of tripterine. The antiproliferative effects of CT-NLC, tripterine-loaded nanostructured lipid carriers (T-NLC), and free tripterine in a human prostatic carcinoma cell line (PC-3) and a mouse prostate carcinoma cell line (RM-1) were evaluated using an MTT assay. The advantage of CT-NLC over T-NLC and free tripterine with regard to antitumor activity in vivo was evaluated in a prostate tumor-bearing mouse model. The induced tumor necrosis factor-alpha and interleukin-6 cytokine content was investigated by enzyme-linked immunosorbent assay to determine the effect of CT-NLC, T-NLC, and free tripterine on immune responses. Histologic and TUNEL assays were carried out to investigate the mechanisms of tumor necrosis and apoptosis.

RESULTS:

CT-NLC, T-NLC, and free tripterine showed high antiproliferative activity in a dose-dependent manner, with an IC50 of 0.60, 0.81, and 1.02 μg/mL in the PC-3 cell line and 0.41, 0.54, and 0.89 μg/mL in the RM-1 cell line after 36 hours. In vivo, the tumor inhibition rates for cyclophosphamide, high-dose (4 mg/kg) and low-dose (2 mg/kg) tripterine, high-dose (4 mg/kg) and low-dose (2 mg/kg) T-NLC, high-dose (4 mg/kg) and low-dose (2 mg/kg) CT-NLC were 76.51%, 37.07%, 29.53%, 63.56%, 48.25%, 72.68%, and 54.50%, respectively, showing a dose-dependent pattern. The induced tumor necrosis factor-alpha and interleukin-6 cytokine content after treatment with CT-NLC and T-NLC was significantly higher than that of high-dose tripterine. Moreover, CT-NLC showed the expected advantage of inducing necrosis and apoptosis in prostate tumor cells.

CONCLUSION:

CT-NLC noticeably enhanced antitumor activity in vitro and in vivo and showed dramatically improved cytotoxicity in normal cells in comparison with free tripterine. In summary, CT-NLC could be used as a promising drug delivery system for the treatment of prostate cancer.

• Authors: Ling Yuan, Congyan Liu, Yan Chen, Zhenhai Zhang, Lei Zhou, Ding Qu
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 8 Pg. 4339-50 ( 2013) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 24235831 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Cell-Penetrating Peptides
• Drug Carriers
• IL6 protein, human
• Interleukin-6
• Lipids
• Pentacyclic Triterpenes
• Triterpenes
• Tumor Necrosis Factor-alpha
• celastrol

Topics

• Animals
• Antineoplastic Agents
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell-Penetrating Peptides (chemistry, pharmacology, toxicity)
• Drug Carriers (chemistry, pharmacology, toxicity)
• Humans
• In Situ Nick-End Labeling
• Interleukin-6 (blood)
• Lipids (chemistry, pharmacology, toxicity)
• Male
• Mice
• Mice, Inbred C57BL
• Nanostructures (chemistry, toxicity)
• Pentacyclic Triterpenes
• Prostatic Neoplasms (metabolism)
• Triterpenes (chemistry, pharmacology, toxicity)
• Tumor Necrosis Factor-alpha (blood)
• Xenograft Model Antitumor Assays