Minocycline in Treating Glioblastoma Multiforme: Far beyond a Conventional Antibiotic

Hamid Mollazadeh,Amir R. Afshari,Amirhossein Sahebkar

doi:10.1155/2020/8659802

Abstract

One of the most lethal forms of CNS pathologies is glioblastoma multiforme (GBM) that represents high invasiveness, uncontrolled proliferation, and angiogenic features. Its invasiveness is responsible for the high recurrence even after maximal surgical interventions. Minocycline is a semisynthetic analog of tetracyclines with potential anti-inflammatory and anticancer effects, distinct from its antimicrobial activity. In this review, we highlight the importance and the cytotoxic mechanisms of minocycline on GBM pathophysiology. Considering the role of certain enzymes in autophagy, apoptosis, tumor cell invasion, and metastatic ability, the possible use of tetracyclines for cancer therapy should be investigated, especially GBM. The present study is, therefore, going to cover the main topics in minocycline pharmacology to date, encouraging its consideration as a new treatment approach for cancer and GBM.

Highlights

Tetracyclines, as broad-spectrum bacteriostatic antibiotics, work against pathologic microorganisms like rickettsia, chlamydia, and mycoplasma pneumonia, as well as against a wide range of Gram-positive, Gram-negative, and anaerobic bacteria [1]. e antibiotic characteristics of tetracyclines were defined at the end of the 1940s; several studies concentrated more recently on their nonantibiotic properties [2]. e second-generation semisynthetic tetracycline analog used for over 30 years is minocycline (7-dimethylamino-6-desoxytertracycline) [3]
In line with the apoptosis mechanisms of minocycline, it has been shown that minocycline prevents primary neurons from radiationinduced apoptosis and promotes radiation-induced autophagy in vitro [115]. ese experimental data further suggest that minocycline has improved its antimetastatic and antitumor effectiveness through antiproliferative, autophagy-inducing, antiangiogenic, matrix metalloproteinases (MMPs) inhibitory, and apoptosis-inducing functions
A study has demonstrated that minocycline activation of phosphoinositide 3-kinase (PI3K) p110α results in cell dysfunction and cell mortality in 9L glioma cells. e findings have proven that PI3Kα activation is essential for minocycline-induced glioblastoma multiforme (GBM) cell death [119]. is result raises serious questions here concerning the development of PI3K inhibitors in treating cancer, especially GBM

Summary

Review Article

Minocycline in Treating Glioblastoma Multiforme: Far beyond a Conventional Antibiotic. Received 29 April 2020; Revised 5 August 2020; Accepted 3 September 2020; Published 17 September 2020. One of the most lethal forms of CNS pathologies is glioblastoma multiforme (GBM) that represents high invasiveness, uncontrolled proliferation, and angiogenic features. Its invasiveness is responsible for the high recurrence even after maximal surgical interventions. Minocycline is a semisynthetic analog of tetracyclines with potential anti-inflammatory and anticancer effects, distinct from its antimicrobial activity. Considering the role of certain enzymes in autophagy, apoptosis, tumor cell invasion, and metastatic ability, the possible use of tetracyclines for cancer therapy should be investigated, especially GBM. E present study is, going to cover the main topics in minocycline pharmacology to date, encouraging its consideration as a new treatment approach for cancer and GBM Considering the role of certain enzymes in autophagy, apoptosis, tumor cell invasion, and metastatic ability, the possible use of tetracyclines for cancer therapy should be investigated, especially GBM. e present study is, going to cover the main topics in minocycline pharmacology to date, encouraging its consideration as a new treatment approach for cancer and GBM

Introduction

Minocycline Autophagy

Intracranial GBM xenograft

Findings

Conclusions