Potent in vitro and xenograft antitumor activity of a novel agent, PV-10, against relapsed and refractory neuroblastoma Journal Article

Authors: Swift, L.; Zhang, C.; Trippett, T.; Narendran, A.
Article Title: Potent in vitro and xenograft antitumor activity of a novel agent, PV-10, against relapsed and refractory neuroblastoma
Abstract: Purpose: Neuroblastoma is the most common extracranial cancer in children. Although the prognosis for low-risk neuroblastoma patients is good, the 5-year survival rates for high-risk and relapsed patients are low. The poor survival rates for these patients demonstrate the need for novel therapeutic approaches to treat this disease. PV-10 is a sterile 10% solution of Rose Bengal that has previously been shown to induce cell death in a range of adult cancers, providing the rationale for studying the activity of PV-10 against neuroblastoma in preclinical studies. Methods: The effects of PV-10 on neuroblastoma were investigated in vitro. Cytotoxicity assays were performed using the alamar blue assay on the following cell lines: SK-N-AS, SK-N-BE(2), IMR5, LAN1, SHEP, and SK-N-SH neuroblastoma cells, SK-N-MC neuroepithelioma cells, and normal primary, BJ, and WI38 fibroblasts. Phase-contrast, fluorescence, and time-lapse video microscopy; flow cytometry; and Western blotting were used to investigate the effects of PV-10 on SK-N-AS and IMR5 cells. Synergy with commonly used anticancer drugs was determined by calculation of combination indices in SK-N-AS and IMR5 cells. Mouse xenograft models of SK-N-AS and IMR5 tumors were also used to evaluate the efficacy of PV-10 in vivo. Results: In vitro preclinical data demonstrate that pharmacologically relevant concentrations of PV-10 are cytotoxic to neuroblastoma cell lines. Studies to investigate target modulation in neuroblastoma cell lines show that PV-10 disrupts lysosomes, decreases the percentage of cells in S phase, and induces apoptosis in a concentration-, time-, and cell-line-dependent manner, and we also identify agents that are synergistic with PV-10. Furthermore, experiments in xenograft mouse models show that PV-10 induces tumor regression in vivo. Conclusion: Our study provides preclinical data on the efficacy of PV-10 against neuroblastoma and provides rationale for the development of an early phase clinical trial of this agent in relapsed and refractory neuroblastoma patients. © 2019 Swift et al.
Keywords: controlled study; human cell; microscopy; doxorubicin; nonhuman; flow cytometry; mouse; animal tissue; cell cycle s phase; etoposide; animal experiment; animal model; vincristine; antineoplastic activity; cytotoxicity; in vitro study; immunotherapy; neuroblastoma; western blotting; radiosensitivity; fluorescence microscopy; cancer classification; concentration response; oncolytic; novel therapeutics; rose bengal; human; female; article; la-n-1 cell line; pv-10; intralesional; pv 10; bj1-htert cell line; imr-5 cell line; sh-ep cell line; sk-n-as cell line; sk-n-be(2) cell line; sk-n-mc cell line; sk-n-sh cell line; wi-38 cell line
Journal Title: OncoTargets and Therapy
Volume: 12
ISSN: 1178-6930
Publisher: Dove Medical Press Ltd  
Date Published: 2019-02-18
Start Page: 1293
End Page: 1307
Language: English
DOI: 10.2147/ott.S191478
PROVIDER: scopus
PMCID: PMC6388978
PUBMED: 30863096
Notes: Article -- Export Date: 1 May 2019 -- Source: Scopus
Citation Impact
MSK Authors
  1. Tanya M Trippett
    110 Trippett