PAMs inhibits monoamine oxidase a activity and reduces glioma tumor growth, a potential adjuvant treatment for glioma

Pei-Chuan Li,Canquan Mao,Chieh-His Wu,Jean Chen Shih,Danzhou Xiangfei,Shih-Yi Chen

doi:10.1186/s12906-020-03041-z

Abstract

BackgroundMonoamine oxidase (MAO) A catalyzes oxidative deamination of monoamine neurotransmitters and dietary amines and regulates brain development and functions. Recently, we showed that MAO A mediates the progression and migration of glioma and MAO A inhibitors reduce glioma cell growth. Glioblastoma (GBM) is a common and most malignant brain tumor which is difficult to treat. Temozolomide (TMZ) is the current standard chemotherapy for glioma, but tumors usually become resistant and recur. So far, no effective therapy for TMZ-resistant glioma is available. Natural plant antimicrobial solution (PAMs) is a Chinese herbal medicine which has been used for decades without toxicity and has multiple medical functions including anti- inflammatory effects. Here, we report the effects of PAMs on glioblastoma growth.MethodsThe growth of TMZ -sensitive (U251S),-resistant (U251R) human glioma cells, and mouse glioma cell line GL-26 were assessed by MTS colorimetric assay, colony formation, and cell migration assays.Male C57BL/6 mice were implanted subcutaneously or intracranial with luciferase-positive mouse glioma GL-26 cells and treated with vehicle; MAO A inhibitor clorgyline (10 mg/kg); TMZ (1 mg/kg); PAMs (48 mg/kg) alone or in combination with TMZ (1 mg/kg) for 14 days. At the end of the treatment, mice were sacrificed, MAO A catalytic activity in tumors was measured, and tumor sizes were determined by imaging and weight.ResultsThese results show that PAMs inhibits MAO A catalytic activity in all three glioma cell lines studied U251S, U251R, and GL-26. PAMs reduced glioma growth and has greater effects in combination with low dose of TMZ than PAMS or TMZ alone in all three cell lines as shown by MTS, colony formation, and cell migration assays. Using the subcutaneous or intracranial GL-26 glioma mouse model, PAMs reduced the tumor growth and MAO A activity, similar to the MAO A inhibitor clorgyline. Combining PAMs with non-toxic dose TMZ increased survival to a greater extent than those of PAMs or TMZ alone.ConclusionsThis is the first study which suggests that PAMs alone or co-administration with low doses of TMZ may be a potential adjuvant to reduce the toxicity of TMZ and to abrogate drug resistance for the effective treatment of glioma.

Highlights

Monoamine oxidase (MAO) A catalyzes oxidative deamination of monoamine neurotransmitters and dietary amines and regulates brain development and functions
Our results showed that 50% inhibitory concentration (IC50) of plant antimicrobial solution (PAMs) is 80.0 μg/ml in GL26 cells and 112.1 μg/ml in LNCaP cells (Fig. 1a)
These results indicate that PAMs inhibits monoamine oxidase A (MAO A) catalytic activity in both glioma and prostate cancer cell lines with almost similar potency

Summary

Introduction

Monoamine oxidase (MAO) A catalyzes oxidative deamination of monoamine neurotransmitters and dietary amines and regulates brain development and functions. Glioblastoma (GBM) is a common and most malignant brain tumor which is difficult to treat. Temozolomide (TMZ) is the current standard chemotherapy for glioma, but tumors usually become resistant and recur. Glioblastoma (GBM) is the most aggressive form of primary brain tumors with a median survival of 14 months from the time of diagnosis [7, 8]. The standard treatments of newly diagnosed glioblastoma (GBM) are surgery, radiation therapy administered concurrently with oral temozolomide (TMZ), and six cycles of adjuvant TMZ therapy [9]. Our previous study showed that MAO A inhibitor clorgyline combined with non-toxic dose TMZ reduced the tumor growth and prolong the survival in animal model [2]

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