Antitumor activity of celastrol nanoparticles in a xenograft retinoblastoma tumor model

Abstract

Background: Celastrol, a Chinese herbal medicine, has shown antitumor activity against various tumor cell lines. However, the effect of celastrol on retinoblastoma has not yet been analyzed. Additionally, the poor water solubility of celastrol restricts further therapeutic applications. The goal of this study was to evaluate the effect of celastrol nanoparticles (CNPs) on r etinoblastoma and to investigate the potential mechanisms involved. Methods: Celastrol-loaded poly(ethylene glycol)-block-poly(ε-caprolactone) nanopolymeric micelles were developed to improve the hydrophilicity of celastrol. The 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulf-ophenyl)-2H tetrazolium monosodium salt (WST-8) assay was used to determine the inhibitory effect of CNPs on SO-Rb 50 cell proliferation in vitro. Immunofluorescence was used to evaluate the apoptotic effect of CNPs on nuclear morphology, and flow cytometry was used to quantify cellular apoptosis. The expression of Bcl-2, Bax, NF-κB p65, and phospo-NF-κB p65 proteins was assessed by Western blotting. A human retinoblastoma xenograft model was used to evaluate the inhibitory effects of CNPs on retinoblastoma in NOD-SCID mice. Hematoxylin and eosin staining was used to assess the apoptotic effects of CNPs on retinoblastoma. Results: CNPs inhibit the proliferation of SO-Rb 50 cells in a dose-and time-dependent manner with an IC 50 of 17.733 µg/mL (celastrol-loading content: 7.36%) after exposure to CNPs for 48 hours. CNPs induce apoptosis in SO-Rb 50 cells in a dose-dependent manner. The expression of Bcl-2, NF-κB p65, and phospo-NF-κB p65 proteins decreased after exposure to CNPs 54.4 µg/mL for 48 hours. Additionally, the Bax/Bcl-2 ratio increased, whereas the expression of Bax itself was not significantly altered. CNPs inhibit the growth of retinoblastoma and induce apoptosis in retinoblastoma cells in mice. Conclusion: CNPs inhibit the growth of retinoblastoma in mouse xenograft model by inducing apoptosis in SO-Rb 50 cells, which may be related to the increased Bax/Bcl-2 ratio and the inhibition of NF-κB. CNPs may represent a potential alternative treatment for retinoblastoma.

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

“…24 In the present study, we evaluated Tripterine, a triterpene compound, is known to inhibit proliferation of a variety of tumor cells, including U937 cells, human prostate cancer cell lines, HL-60 cells, and human melanoma cells. 25 In the present study, MTT assay results indicated that CT-NLC could enhance the antiproliferative effect of tripterine in PC-3 and RM-1 cells in a dose-dependent manner. In terms of IC 50 , both CT-NLC and T-NLC had a more remarkable inhibitory effect on the proliferation of PC-3 and RM-1 cells than did the tripterine suspension.…”

ER stress-mediated apoptosis induced by celastrol in cancer cells and important role of glycogen synthase kinase-3β in the signal network

“…6, 7, 8, 9, 10, 11, 12, 13, 14, 15 In our previous report, we found that celastrol could induce different kinds of cell death including apoptosis, autophagy and paraptosis in cancer cells. 6 Importantly, our study using inhibitors of apoptosis, autophagy and paraptosis indicated that apoptosis was the type of cell death that mainly contributed to the cytotoxicity of celastrol.…”

Positively charged micelles based on a triblock copolymer demonstrate enhanced corneal penetration

“…13,16 Recently, polymeric micelles have been used for ocular drug delivery to improve the drug release. 17,18 Drug-loaded polymeric micelles offer favorable biological properties, such as biocompatibility, biodegradability, mucoadhesiveness, nontoxicity, and controlled drug release. 19 Topical formulations of drug-loaded polymeric micelles hold significant promise for ophthalmic drug delivery.…”

“…30 PEG-PCL micelles have been widely used as drug-delivery carriers to improve the solubility of hydrophobic drugs. 17,31 In addition, PEI (Mw 1,800 Da) chains have been conjugated to classic PEG-PCL amphiphilic compounds to create superior cationic polymers due to their ability to develop molecular attraction forces via electrostatic interactions between the positively charged amino groups of PEI and the negatively charged sialic acid residues of mucin. There are also reports on the use of polymeric micelles prepared with mPEG-PCL-g-PEI copolymer for the codelivery of chemotherapy drugs and nucleic acid drugs into cancerous tumors.…”