Abstract

Photodynamic therapy (PDT) has recently attracted interest as an innovative and adjuvant treatment for different cancers including malignant gliomas. Among these, Glioblastoma (GBM) is the most prevalent neoplasm in the central nervous system. Despite conventional therapeutic approaches that include surgical removal, radiation, and chemotherapy, GBM is characterized by an extremely poor prognosis and a high rate of recurrence. PDT is a physical process that induces tumor cell death through the genesis and accumulation of reactive oxygen species (ROS) produced by light energy interaction with a photosensitizing agent. In this contribution, we explored the potentiality of the plant alkaloid berberine (BBR) as a photosensitizing and cytotoxic agent coupled with a PDT scheme using a blue light source in human established astrocytoma cell lines. Our data mainly indicated for the combined BBR-PDT scheme a potent activation of the apoptosis pathway, through a massive ROS production, a great extent of mitochondria depolarization, and the sub-sequent activation of caspases. Altogether, these results demonstrated that BBR is an efficient photosensitizer agent and that its association with PDT may be a potential anticancer strategy for high malignant gliomas.

Highlights

  • Cells were routinely grown as monolayers at 37 ◦ C in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% fetal bovine serum (FBS) and 100 U/mL of penicillin and 100 μg/mL

  • Of penicillin-streptomycin, under atmosphere controlled at 5% CO2

  • Reduction in astrocytoma cell line viability was observed after 24 h administration of BBR in a range of 20–200 μg/mL [28,29,30]

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Summary

Introduction

Despite a multitude of research efforts, ongoing therapeutic strategies, including for example first-line chemotherapeutic compounds as temozolomide or carmustine, have not determined a significantly higher efficacy in clinics mostly due to limited pharmacokinetics and to GBM intrinsic and acquired resistance to the treatments [4]. In this regard, the large extent of genetic and phenotypic heterogeneity among GBMs [5] has constituted a biological hurdle for the efficacy of the therapeutic agents toward tumor cells [6]. Clinical applications of photodynamic therapy (PDT) in oncologic contexts including GBM have gained increased attention [8,9,10]

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