Natural products: a hope for glioblastoma patients

Abstract

Glioblastoma (GBM) is one of the most aggressive malignant tumors with an overall dismal survival averaging one year despite multimodality therapeutic interventions including surgery, radiotherapy and concomitant and adjuvant chemotherapy. Few drugs are FDA approved for GBM, and the addition of temozolomide (TMZ) to standard therapy increases the median survival by only 2.5 months. Targeted therapy appeared promising in in vitro monolayer cultures, but disappointed in preclinical and clinical trials, partly due to the poor penetration of drugs through the blood brain barrier (BBB). Cancer stem cells (CSCs) have intrinsic resistance to initial chemoradiation therapy (CRT) and acquire further resistance via deregulation of many signaling pathways. Due to the failure of classical chemotherapies and targeted drugs, research efforts focusing on the use of less toxic agents have increased. Interestingly, multiple natural compounds have shown antitumor and apoptotic effects in TMZ resistant and p53 mutant GBM cell lines and also displayed synergistic effects with TMZ. In this review, we have summarized the current literature on natural products or product analogs used to modulate the BBB permeability, induce cell death, eradicate CSCs and sensitize GBM to CRT.

Crocetin Extracted from Saffron Shows Antitumor Effects in Models of Human Glioblastoma

“…Interestingly, various authors illustrated how many natural agents exhibited antitumor action by affecting the role of HDAC proteins and other regulators of gene expression. Over recent years, a series of work introduced the effects of different natural compounds on GBM [22,23]. Among these natural agents, a saffron extract (SE) compound named crocetin (CCT) raised significant interest due to its capacity to impair the survival and progression of different cancer types [24,25].…”

Hyperforin induces apoptosis through extrinsic/intrinsic pathways and inhibits EGFR/ERK/NF‐κB‐mediated anti‐apoptotic potential in glioblastoma

“…Trogrlić et al demonstrated herbal medicines induced tumor regression and prolonged survival in glioblastoma patients 6 . In addition, in cells and animal models indicated several herbal compounds inhibited progression of glioblastoma through induction of apoptosis, arrest of cell cycle progression, promotion of anticancer immunity, and disruption of oncogenic signaling transduction 7,8 . Many herbal compounds were indicated to modulate antidepressant effect and attenuate hypoxic stress or toxicity agents‐induced brain damage in animal models 9,10 .…”

Prospect of natural products in glioma: A novel avenue in glioma management

“…There may be only one compound eligible for clinical approval among those natural compounds reported in the literature. Many natural compounds have a direct chemopreventive effect on glioma, but there are some compounds that can help to overcome the significant limitations of glioma therapy by sensitizing glioma cells to chemotherapeutic agents or permeabilizing BBB for chemotherapeutic agents (Vengoji, Macha, Batra, & Shonka, ).…”

“…CSCs are mainly responsible for tumor recurrence in glioma. Eckol, a phlorotannin, exhibits anti‐CSCs property in U87 and U373 cells (Vengoji et al, ).…”

“…Usually, drugs are applied at a higher concentration in glioma treatment to overcome the hindrance of BBB and to achieve adequate drug concentration in tumor tissue (Desai & Bhushan, ). But this higher drug concentration results in toxicity to organs of the body (Vengoji et al, ). Therefore, researchers are trying to explore the efficacy of natural compounds in glioma therapy.…”