Phytotherapy for the Treatment of Glioblastoma: A Review

Mian, Shan Yasin; Nambiar, Abhishek; Kaliaperumal, Chandrasekaran

doi:10.3389/fsurg.2022.844993

Cited by 7 publications

(3 citation statements)

References 18 publications

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“…[4, 5] Most GBM exhibit EGFR amplification, however EGFR inhibitors have failed in clinical trials due to intratumoral heterogeneity and poor blood-brain-barrier (BBB) permeability. [4, 5] Furthermore the modulation of BBB by glioma stem cell transcription factors confer to GBM chemoresistance [4–6] Currently there is a significant lack of treatment options for GBM and several novel therapeutics approaches [4, 28] including phytochemicals [35] are being explored. Hence to address this therapeutic gap, having established the merit of targeting SERPINE1 for the treatment of GBM, in this study we propose potential lead-like molecules derived from Calotropis gigantea which can be developed for clinical use.…”

Section: Discussionmentioning

confidence: 99%

Analysing the role of SERPINE1 network in the pathogenesis of human glioblastoma

Kaliaperumal

Khosravi

Kumar

2022

Preprint

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Background: Glioblastoma multiforme (GBM) is one of the most aggressive and difficult to treat brain tumour in humans with a 5 year survival rate of less than 6%. SERPINE1 is a novel tumour receptor found on GBM that modulates the progression of this cancer through growth signals and remodelling of the extracellular matrix. Hence, we investigated the role of SERPINE1 and its network proteins in pathogenesis of GBM and assessed its targetability. Material and methods: Network proteins of SERPINE1 in homo sapiens was identified using the String database, and the affinity of the protein-protein interaction of this network was analysed using Chimera software. The expression profile of SERPINE1 in the different brain regions was evaluated to correlate its relevance to GBM pathology. Selected small molecules from Calotropis gigantea were screened using AutoDock vina to assess targetability of human SERPINE1. Results: VTN, PLG, TGFB1, VWF, FGF2 and CXCR1 were identified as the major network proteins of SERPINE1. The strongest interaction was observed between SERPINE1 and FGF2 (42884 H-bonds) followed by CXCR1 (20279 H-bonds). Our results suggest that SERPINE1 and its network proteins identified here play a vital role in GBM development and progression through brain parenchyma by creating the prime microenvironment for carcinogenesis, tumour invasion and migration. The highest expression of SERPINE1 was observed in the pons, medulla, midbrain, corpus callosum and spinal cord. Expression of SERPINE1 was consistent with high grade lesions of GBM, suggesting association of SERPINE1 with advanced stages of GBM. The selected small molecules from Calotropis gigantea were observed to have therapeutically feasible binding affinity (140 - 550 microM) and predicted efficacy (290 - 1115 microM) against human SERPINE1. Conclusion: SERPINE1 plays a vital role in the progression of GBM through its critical network proteins identified in this study. The expression of SERPINE1 aligns with the advanced stages of GBM. Small molecules from Calotropis gigantea tested in this study can serve as lead compounds for developing novel anti- SERPINE1 therapeutics for advanced stages of GBM.

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Section: Discussionmentioning

confidence: 99%

Analysing the role of SERPINE1 network in the pathogenesis of human glioblastoma

Kaliaperumal

Khosravi

Kumar

2022

Preprint

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“…A strong and reliable correlation was found between the antioxidant and anticancer activities of different plant extracts [22,23]. Therefore, it should be assumed that bearberry leaf extracts, which, in previous studies showed antioxidant activity due to the presence of arbutin, hydroquinone, methylarbutin, hyperoside, and flavonoids [19,24,25], will also be active against glioblastoma, which is one of the most perplexing cancers with one of the worst prognoses in modern medicine [26]. Therefore, the use of diversified raw materials and various extractant types is justified because the varied chemical composition of extracts determines their biological activity.…”

Section: Introductionmentioning

confidence: 92%

Phytochemical Profiles and Anti-Glioma Activity of Bearberry Arctostaphylos uva-ursi (L.) Spreng. Leaf Extracts

Sugier,

Jakubowicz-Gil,

Zając

et al. 2024

Applied Sciences

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The use of diversified raw materials and various extractant types is justified because the varied chemical composition of extracts obtained via extraction determines their biological activity. Therefore, the objective of this study was (i) to characterize the chemical profile of two types of bearberry extracts (70% ethanolic and water) and (ii) to investigate the biological activity of the analyzed extracts through an assessment of their possible proapoptotic effects on glioma cell lines. The HPLC-UV analysis of individual compounds was performed for the determination of the phytochemical profile of the bearberry extracts, and their total phenolic content (TPC) and total flavonoid content (TFC) were determined spectrophotometrically. The induction of apoptosis, autophagy, and necrosis in anaplastic astrocytoma MOGGCCM and human glioblastoma LN229 cell lines were investigated. The results indicated that the ethanolic (Et) and aqueous (Aq) extracts had different chemical profiles. The TPC in the Et was ca. 60% higher than in the Aq. Similarly, the TFC and methylarbutin (mARB) concentrations were significantly higher in the Et. On the other hand, the concentration of hydroquinone (HQ) was ca. 70% and that of corilagin (COR) was ca. 100% higher in the Aq. In turn, the presence of ursolic acid (UA) and oleanolic acid (OA) was confirmed solely in the Et. In contrast to Aq, Et demonstrated high proapoptotic activity. At the concentration of 2 µL/mL, the level of apoptosis varied between 14.7% and 26% in the case of the MOGGCCM cells and between 12.3% and 33.3% in the case of the LN229 cell line. The knowledge and information obtained in this study indicate a need for further research on the anticancer effect of the studied bearberry phytochemicals on the MOGGCCM and LN229 cell lines and for the elucidation of their molecular anticancer mechanisms.

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“…Systemic delivery of anti-miR-21 resulted in reduced proliferation, tumor growth inhibition, and increased apoptosis in a mouse model of GBM [ 204 ]. Lipid nanoparticles containing miR-124 have been found to prolong survival, prevent tumor recurrence, and induce immune memory [ 53 , 205 , 206 , 207 , 208 , 209 ].…”

Section: The Use Of Mirnas In Gbm Therapymentioning

confidence: 99%

microRNAs (miRNAs) in Glioblastoma Multiforme (GBM)—Recent Literature Review

Makowska

Smolarz

Romanowicz

2023

IJMS

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Glioblastoma multiforme (GBM) is the most common, malignant, poorly promising primary brain tumor. GBM is characterized by an infiltrating growth nature, abundant vascularization, and a rapid and aggressive clinical course. For many years, the standard treatment of gliomas has invariably been surgical treatment supported by radio- and chemotherapy. Due to the location and significant resistance of gliomas to conventional therapies, the prognosis of glioblastoma patients is very poor and the cure rate is low. The search for new therapy targets and effective therapeutic tools for cancer treatment is a current challenge for medicine and science. microRNAs (miRNAs) play a key role in many cellular processes, such as growth, differentiation, cell division, apoptosis, and cell signaling. Their discovery was a breakthrough in the diagnosis and prognosis of many diseases. Understanding the structure of miRNAs may contribute to the understanding of the mechanisms of cellular regulation dependent on miRNA and the pathogenesis of diseases underlying these short non-coding RNAs, including glial brain tumors. This paper provides a detailed review of the latest reports on the relationship between changes in the expression of individual microRNAs and the formation and development of gliomas. The use of miRNAs in the treatment of this cancer is also discussed.

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Phytotherapy for the Treatment of Glioblastoma: A Review

Cited by 7 publications

References 18 publications

Analysing the role of SERPINE1 network in the pathogenesis of human glioblastoma

Analysing the role of SERPINE1 network in the pathogenesis of human glioblastoma

Phytochemical Profiles and Anti-Glioma Activity of Bearberry Arctostaphylos uva-ursi (L.) Spreng. Leaf Extracts

microRNAs (miRNAs) in Glioblastoma Multiforme (GBM)—Recent Literature Review

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