Phytochemical-Mediated Glioma Targeted Treatment: Drug Resistance and Novel Delivery Systems

Abstract

Glioma, especially its most malignant type, Glioblastoma (GBM), is the most common and the most aggressive malignant tumour in the central nervous system. Currently, we have no specific therapies that can significantly improve its dismal prognosis. Recent studies have reported promising in vitro experimental results of several novel glioma-targeting drugs; these studies are encouraging to both researchers and patients. However, clinical trials have revealed that novel compounds that focus on a single, clear glioma genetic alteration may not achieve a satisfactory outcome or have side effects that are unbearable. Based on this consensus, phytochemicals that exhibit multiple bioactivities have recently attracted much attention. Traditional Chinese medicine and traditional Indian medicine (Ayurveda) have shown that phytocompounds inhibit glioma angiogenesis, cancer stem cells and tumour proliferation; these results suggest a novel drug therapeutic strategy. However, single phytocompounds or their direct usage may not reverse comprehensive malignancy due to poor histological penetrability or relatively unsatisfactory in vivo efficiency. Recent research that has employed temozolomide combination treatment and Nanoparticles (NPs) with phytocompounds has revealed a powerful dual-target therapy and a high blood-brain barrier penetrability, which is accompanied by low side effects and strong specific targeting. This review is focused on major phytocompounds that have contributed to glioma-targeting treatment in recent years and their role in drug resistance inhibition, as well as novel drug delivery systems for clinical strategies. Lastly, we summarize a possible research strategy for the future.

Markedly divergent effects of Ouabain on a Temozolomide-resistant (T98G) vs. a Temozolomide-sensitive (LN229) Glioblastoma cell line

“…This might be due to differences between the cell environments and additional signaling factors in vivo, which may amplify or add to the Ouabain effect [ 96 , 97 ]. An interesting approach would be to combine Ouabain with other phytochemicals shown to be active in GBM [ 98 – 100 ] and to deliver them with the recently investigated nanoparticle method [ 98 , 101 ].…”

Research progress of anti-glioma chemotherapeutic drugs (Review)

“…TMZ is a first line chemotherapy drug for glioma ( 31 ) and a precursor alkylating agent ( 32 ). In addition, TMZ is a small molecule and lipophilic substance that can be taken orally and readily traverses through the BBB ( 33 , 34 ). Data from previous preclinical studies ( 16 , 27 , 35 – 51 ) ( Table I ) showed that it can exert anticancer activity.…”

Systematic characterization and biological functions of non‐coding RNAs in glioblastoma

“…Apart from surgical treatment, radiotherapy and chemotherapy are also important means to treat GBM. However, GBM cells have been clinically shown in recent years to be resistant to radiotherapy and chemotherapy, resulting in poor prognosis of patients 51,52 . Previous studies have found that miRNAs play crucial roles in regulating the radiation and drug resistance of GBM cells.…”