Modulation of the ubiquitin‐proteasome system by phytochemicals: Therapeutic implications in malignancies with an emphasis on brain tumors

Abstract

Regarding the multimechanistic nature of cancers, current chemo‐ or radiotherapies often fail to eradicate disease pathology, and frequent relapses or resistance to therapies occur. Brain malignancies, particularly glioblastomas, are difficult‐to‐treat cancers due to their highly malignant and multidimensional biology. Unfortunately, patients suffering from malignant tumors often experience poor prognoses and short survival periods. Thus far, significant efforts have been conducted to discover novel and more effective modalities. To that end, modulation of the ubiquitin‐proteasome system (UPS) has attracted tremendous interest since it affects the homeostasis of proteins critically engaged in various cell functions, for example, cell metabolism, survival, proliferation, and differentiation. With their safe and multimodal actions, phytochemicals are among the promising therapeutic tools capable of turning the operation of various UPS elements. The present review, along with an updated outline of the role of UPS dysregulation in multiple cancers, provided a detailed discussion on the impact of phytochemicals on the UPS function in malignancies, especially brain tumors.

Action of Curcumin on Glioblastoma Growth: A Systematic Review with Meta-Analysis of Animal Model Studies

“…The decrease in AP-1 activity may result in decreased invasion since this TF induces the expression of MMPs. A reduction in NF-κB may be a consequence of decreased PKB/Akt phosphorylation [15]-resulting in decreased NF-κB activation by Akt-and decreased proteasome degradation of the NF-kB inhibitor IκB [54], induced by curcumin. Decreased NF-κB activity-which is upregulated in glioma-induced by curcumin may result in decreased proliferation, cell survival, angiogenesis, inflammation, and increased apoptosis since this TF directly regulates the expression of genes involved in these processes [55].…”

Recent Advances in Curcumin-Based Combination Nanomedicines for Cancer Therapy

“…Chemotherapy medicines, e.g., docetaxel (DTX), irinotecan, 5-fluorouracil (5-FU), cisplatin, and paclitaxel (PTX), are utilized in treating diverse cancers; nevertheless, their efficacies are confined, owing to the emergence of drug resistance, inducing non-selective toxicity and producing significant adverse reactions [5]. It is expected that the efficiency of pharmacological therapy will improve when combined with treatments that use phytochemicals, and the unwanted effects will become less severe as a result [6][7][8]. For instance, the findings showed that curcumin (Cur, an active ingredient from Curcuma longa with multiple biological effects [9][10][11][12][13][14][15][16][17]), in combination with chemotherapeutics, had a wider range of anti-cancer action and a lower risk of severe side effects than standard chemotherapy medications [18,19].…”