Page 72 - Read Online

Fonseka et al. J Cancer Metastasis Treat 2020;6:7 Journal of Cancer
DOI: 10.20517/2394-4722.2019.024 Metastasis and Treatment

Original Article Open Access

Combinatorial treatment of curcumin or silibinin
with doxorubicin sensitises high-risk neuroblastoma

Pamali Fonseka , Lahiru Gangoda , Mohashin Pathan , Di Giannatale Angela , Suresh Mathivanan 1
1,#
1,#
1
2
1 Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria
3086, Australia.
2 Department of Hematology/Oncology, Bambino Gesù Children’s Hospital, IRCCS, Rome 00165, Italy.
# Authors contributed equally.
Correspondence to: Prof. Suresh Mathivanan, Department of Biochemistry and Genetics, La Trobe Institute for Molecular
Science, La Trobe University, Bundoora, Victoria 3086, Australia. E-mail: s.mathivanan@latrobe.edu.au

How to cite this article: Fonseka P, Gangoda L, Pathan M, Angela DG, Mathivanan S. Combinatorial treatment of curcumin or
silibinin with doxorubicin sensitises high-risk neuroblastoma. J Cancer Metastasis Treat 2020;6:7.
http://dx.doi.org/10.20517/2394-4722.2019.024

Received: 16 Aug 2019 First Decision: 20 Nov 2019 Revised: 17 Feb 2020 Accepted: 2 Mar 2020 Published: 13 Mar 2020
Science Editor: Godefridus J. Peters Copy Editor: Jing-Wen Zhang Production Editor: Jing Yu

Abstract
Aim: Neuroblastoma is a pediatric cancer of the sympathetic nervous system. Using various parameters including
stage of the disease, amplification status of N-Myc, DNA index and histopathology, neuroblastoma can be stratified
into low- and high-risk groups. Recent advances in treatment have significantly improved the survival rate of low-
risk neuroblastoma patients. However, the overall survival rate of high-risk neuroblastoma group, especially N-Myc
amplified patients, is poor. Moreover, the survivors of both low- and high-risk neuroblastoma manifest adverse side
effects to chemotherapy and thus their quality of life is impaired. Considering all these factors, there is an urgent
need to develop therapeutic strategies with natural compounds to improve the survival rate and to reduce the side
effects. In this study, we hypothesised that the mesenchymal nature of neuroblastoma cells is a reason, at least in
part, for the aggressive and treatment resistant phenotype.

Method: In order to validate our hypothesis, we used publicaly available RNA-Seq data, in vitro assays and xenograft
mouse models.

Results: Using a combinatorial treatment of mesenchymal-to-epithelial inducers (curcumin or silibinin) with
doxorubicin significantly increased the cell death in a panel of neuroblastoma cells in vitro. Follow up analysis in
vivo, confirmed the therapeutic benefit of utilising the combination of curcumin with doxorubicin. The combinatorial
therapy significantly reduced the tumor burden and increased the survival of mice implanted with high-risk
neuroblastoma cells.
© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

www.jcmtjournal.com