Natural substances to potentiate canonical glioblastoma chemotherapy

Abstract

Glioblastoma multiforme (GBM) is the most frequent primary malignant brain tumour prevalent in humans, that exhibits aggressive cell proliferation and rapid invasion of normal brain tissue. Despite aggressive therapeutic approaches consisting of maximum safe surgical resection followed by radio-chemotherapy with temozolomide (TMZ), more than 95% of GBM patients die within 5 years after diagnosis. In most cases, the therapy is not able to counteract the growth and invasiveness of the tumour, which relapses after an interval of time that varies from patient to patient. An increasing number of evidence indicates that natural substances exhibited effective anti-tumour functions and might be successfully used in the treatment of GBM. This review summarizes some natural substances: lactoferrin, hispolon, aloe-emodin and tea tree oil; all these show a growth inhibition and synergistic effect when together with TMZ, (the most commonly used alkylating drug for the treatment of glioblastoma) were administered to U87MG glioblastoma cell line in vitro and in murine animal model. U87MG cell growth was monitored by daily cell count after treatments with the substances mentioned above and growth analysis showed that all drugs significantly decrease proliferation of U87MG in a time- and dose-dependent manner. FACS analysis demonstrates a block of cell cycle in S, G2/M or G0/G1 phases. These substances mediate multiple processes including apoptosis by releasing the inducing factor: PARP. Natural compounds, in combination with conventional chemotherapy TMZ, are a powerful approach to improve the effectiveness of brain cancer treatment.

Graphical Abstract

Keywords:

• brain cancer
• lactoferrin
• hispolon
• aloe-emodin
• tree tea oil
• glioblastoma
• natural drug

Acknowledgments

I am grateful to Arianna de Silva and Alba di Mambro for their English typing corrections. A great thanks to M. Antonietta Oliva and Rossella Rotondo for assisting me throughout the writing of the manuscript.

Disclosure statement

The author reports no conflict of interest.

Additional information

Funding

The researchers did not receive any specific grants from funding agencies in the public commercial or not-for-profit sectors.

Notes on contributors

Antonietta Arcella

Dr. Antonietta Arcella is the Head of Molecular Neuropathology Laboratory at IRCCS Neuromed. She obtained her Bachelor's Degree in Biological Sciences and received a PhD in Biochemistry and Medical Biotechnology from the University of Naples Federico II. Since 2003 she is focused in the development of new in vitro and in vivo GBM modelling systems: preparation of glioblastoma cell cultures starting from the mechanical and enzymatic dissection of the patient's biopsy, preparation of glial stem cell cultures and neurospheres, stereotaxic implantation of GBM cells in the caudate nucleus of nude CD1 mice for the in vivo study of new mechanisms and substances for the blocking of GBM cell growth. In this regard, she is particularly interested in the molecular characterization of gliomas and the association with drug resistance as well as in the evaluation of adjuvant therapies. Dr.Arcella has authored numerous scientific papers concerning the molecular features of glioblastoma, new adjuvant therapies for the treatment of brain tumours besides novel drug delivery systems to increase the effectiveness of conventional anticancer drugs in the fight against this incurable neoplasm.

Massimo Sanchez

Dr. Massimo Sanchez obtained is PhD in Biochemistry and Medical Biotechnology from the University of Naples Federico II. He is currently the responsible of Core Facility at Instituto Superiore di Sanità (ISS),that performed flow cytometry analysis.