Calcium Entry through TRPV1: A Potential Target for the Regulation of Proliferation and Apoptosis in Cancerous and Healthy Cells

Zhai, Kevin; Líšková, Alena; Kubatka, Peter; Büsselberg, Dietrich

doi:10.3390/ijms21114177

Cited by 85 publications

(72 citation statements)

References 152 publications

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“…Cell fate is regulated by a delicate balance between proliferation and death. In GBM and other tumor cells, growth factors, chemokine ligands, and other upstream signals mediate a shift towards excessive growth and proliferation ( Figure 4 ; Table 3 ) [ 62 ]. Growth factors, including tumor growth factor βeta (TGF-β), insulin-like growth factor (IGF), hepatoma-derived growth factor (HDGF), and glial cell-derived neurotrophic factor (GDNF), are upregulated in GBM and contribute to downstream Ras/Raf/MEK/ERK and PI3K/Akt signaling.…”

Section: Mechanistic Effects Of Natural Compounds On Glioblastomamentioning

confidence: 99%

Natural Compounds in Glioblastoma Therapy: Preclinical Insights, Mechanistic Pathways, and Outlook

Zhai

Siddiqui

Abdellatif

et al. 2021

Cancers

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Glioblastoma (GBM) is an aggressive, often fatal astrocyte-derived tumor of the central nervous system. Conventional medical and surgical interventions have greatly improved survival rates; however, tumor heterogeneity, invasiveness, and chemotherapeutic resistance continue to pose clinical challenges. As such, dietary natural substances—an integral component of the lifestyle medicine approach to chronic diseases—are examined as potential chemotherapeutic agents. These heterogenous substances exert anti-GBM effects by upregulating apoptosis and autophagy, inducing cell cycle arrest, interfering with tumor metabolism, and inhibiting proliferation, neuroinflammation, chemoresistance, angiogenesis, and metastasis. Although these beneficial effects are promising, natural substances’ efficacy in GBM is constrained by their bioavailability and blood–brain barrier permeability; various chemical formulations are proposed to improve their pharmacological properties. Many of the reviewed substances are available as over-the-counter dietary supplements, underscoring their viability as lifestyle interventions. However, clinical trials remain necessary to substantiate the in vitro and in vivo properties of natural substances.

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Section: Mechanistic Effects Of Natural Compounds On Glioblastomamentioning

confidence: 99%

Natural Compounds in Glioblastoma Therapy: Preclinical Insights, Mechanistic Pathways, and Outlook

Zhai

Siddiqui

Abdellatif

et al. 2021

Cancers

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“…TRPV channels form homo- or heterotetrameric complexes and are non-selective cation channels (Startek et al, 2019 ). The TRPV subfamily consists of six members (TRPV1-6) that are located mostly on the plasma membrane (Zhai et al, 2020 ). Recent studies on pathological TRPV1 expression in the brain have been performed (Mickle et al, 2015 ).…”

Section: Brain Disordersmentioning

confidence: 99%

The Role of TRP Channels and PMCA in Brain Disorders: Intracellular Calcium and pH Homeostasis

Hwang

Lee

Kim

2021

Front. Cell Dev. Biol.

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Brain disorders include neurodegenerative diseases (NDs) with different conditions that primarily affect the neurons and glia in the brain. However, the risk factors and pathophysiological mechanisms of NDs have not been fully elucidated. Homeostasis of intracellular Ca2+ concentration and intracellular pH (pHi) is crucial for cell function. The regulatory processes of these ionic mechanisms may be absent or excessive in pathological conditions, leading to a loss of cell death in distinct regions of ND patients. Herein, we review the potential involvement of transient receptor potential (TRP) channels in NDs, where disrupted Ca2+ homeostasis leads to cell death. The capability of TRP channels to restore or excite the cell through Ca2+ regulation depending on the level of plasma membrane Ca2+ ATPase (PMCA) activity is discussed in detail. As PMCA simultaneously affects intracellular Ca2+ regulation as well as pHi, TRP channels and PMCA thus play vital roles in modulating ionic homeostasis in various cell types or specific regions of the brain where the TRP channels and PMCA are expressed. For this reason, the dysfunction of TRP channels and/or PMCA under pathological conditions disrupts neuronal homeostasis due to abnormal Ca2+ and pH levels in the brain, resulting in various NDs. This review addresses the function of TRP channels and PMCA in controlling intracellular Ca2+ and pH, which may provide novel targets for treating NDs.

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“…Flavonoids, for example, suppress cancer through modulation of extracellular matrix (ECM) proteins, inhibition of the epithelial–mesenchymal transition (EMT), and inhibition of cancer cell metabolism [ 13 , 14 ]. Plant phenolic acids and lichens upregulate apoptosis, inhibit proliferation and metastasis, and induce cell cycle arrest, while vanilloids such as capsaicin exert anticancer effects through the modulation of intracellular calcium signaling [ 15 , 16 , 17 ]. Significantly, several natural substances are effective against NB cells in vitro.…”

Section: Natural Substances In the Prevention And Treatment Of Neumentioning

confidence: 99%

Curcumin’s Beneficial Effects on Neuroblastoma: Mechanisms, Challenges, and Potential Solutions

et al. 2020

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Curcumin, a natural polyphenolic compound derived from the South Asian turmeric plant (Curcuma longa), has well-characterized antioxidant, anti-inflammatory, anti-protein-aggregate, and anticancer properties. Neuroblastoma (NB) is a cancer of the nervous system that arises primarily in pediatric patients. In order to reduce the multiple disadvantages and side effects of conventional oncologic modalities and to potentially overcome cancer drug resistance, natural substances such as curcumin are examined as complementary and supportive therapies against NB. In NB cell lines, curcumin by itself promotes apoptosis and cell cycle arrest through the suppression of serine–threonine kinase Akt and nuclear factor kappa of activated B-cells (NF-κB) signaling, induction of mitochondrial dysfunction, and upregulation of p53 and caspase signaling. While curcumin demonstrates anti-NB efficacy in vitro, cross-validation between NB cell types is currently lacking for many of its specific mechanistic activities. Furthermore, curcumin’s low bioavailability by oral administration, poor absorption, and relative insolubility in water pose challenges to its clinical introduction. Numerous curcumin formulations, including nanoparticles, nanocarriers, and microemulsions, have been developed, with these having some success in the treatment of NB. In the future, standardization and further basic and preclinical trials will be required to ensure the safety of curcumin formulations. While the administration of curcumin is clinically safe even at high doses, clinical trials are necessary to substantiate the practical efficacy of curcumin in the prevention and treatment of NB.

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Calcium Entry through TRPV1: A Potential Target for the Regulation of Proliferation and Apoptosis in Cancerous and Healthy Cells

Cited by 85 publications

References 152 publications

Natural Compounds in Glioblastoma Therapy: Preclinical Insights, Mechanistic Pathways, and Outlook

Natural Compounds in Glioblastoma Therapy: Preclinical Insights, Mechanistic Pathways, and Outlook

The Role of TRP Channels and PMCA in Brain Disorders: Intracellular Calcium and pH Homeostasis

Curcumin’s Beneficial Effects on Neuroblastoma: Mechanisms, Challenges, and Potential Solutions

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