Modulation of Calcium Signaling in Glioblastoma Multiforme: A Therapeutic Promise for Natural Products

Abstract

: Glioblastoma multiforme (GBM) continues as one of the most lethal cerebral cancers despite standard therapeutic modalities, such as maximum surgical resection and chemoradiation. The minimal effectiveness of existing therapies necessitates the development of additional drug candidates that could improve the prognosis of GBM patients. Accumulating evidence suggests that calcium (Ca2+) is involved in the processes of cell proliferation, metastasis, angiogenesis, migration, and invasiveness. Therefore, Ca2+ could serve as a crucial regulator of tumorigenesis and a potential treatment target in GBM. In this context, specific natural products are known to modulate Ca2+ signaling pathways implicated in tumor growth, apoptosis, angiogenesis, and development of GBM. Here, we focus on the function of Ca2+ as a therapeutic target in GBM and review certain natural products that affect the signaling pathways of Ca2+.

The regulatory pattern of target gene expression by aberrant enhancer methylation in glioblastoma

“…For the KEGG pathway analysis, we found that these target genes that might be regulated by hypomethylated enhancer regions were enriched in some GBM-related KEGG pathways. As the significantly enriched pathway (hsa04020, hsa04724) in this study, Afshari et al [ 35 ] showed that calcium signaling pathway is involved in the processes of cell proliferation, metastasis, angiogenesis, migration, and invasiveness. Moreover, glutamatergic and calcium signaling may promote glioblastoma formation by metabolic reprogramming and genetic switching or upregulate the levels intracellular Ca 2+ to increase glutamate release [ 36 ].…”

Zerumbone, a ginger sesquiterpene, inhibits migration, invasion, and metastatic behavior of human malignant glioblastoma multiforme in vitro

“…As the most prominent brain tumor for adults, GBM presents considerable invasion ability, extreme aggressive behavior, and chemoradiation resistance 24,25 . Total surgical resection accompanied by radiotherapy and concurrent chemotherapy with alkylating agent TMZ remains the primary care line, extending patients' survival by just 2 months in total 26,27 . Novel therapeutic strategies that boost clinical outcomes are therefore desperately needed 28 .…”

“…24,25 Total surgical resection accompanied by radiotherapy and concurrent chemotherapy with alkylating agent TMZ remains the primary care line, extending patients' survival by just 2 months in total. 26,27 Novel therapeutic strategies that boost clinical outcomes are therefore desperately needed. 28 The present study assessed Zerumbone to suppress GBM cancer cell development in vitro.…”

Tumor-Inhibitory Effects of Zerumbone Against HT-29 Human Colorectal Cancer Cells

“…5 However, due to the unwanted side effects of chemotherapeutic agents and poor prognosis after treatment with these conventional methods, there is an urgent need to find out new potential anti-cancer compounds with low adverse effects and high effectiveness. 6,7 In recent years, herbal medicines and natural products have received more attention in the treatment of many cancers due to their low toxicity, high efficacy, and broad-spectrum properties. [8][9][10] One of these natural compounds that have shown capability in the treatment of cancer is zerumbone.…”

“…5 However, due to the unwanted side effects of chemotherapeutic agents and poor prognosis after treatment with these conventional methods, there is an urgent need to find out new potential anti-cancer compounds with low adverse effects and high effectiveness. 6,7…”