Antioxidant vitamins promote anticancer effects on low‐concentration methotrexate‐treated glioblastoma cells via enhancing the caspase‐3 death pathway

Yiang, Giou‐Teng; Chen, Tsu-Yi; Chen, Cian; Hung, Yu‐Ting; Hsueh, Kuan-Chun; Wu, Tsai‐Kun; Pan, Y.; Chien, Yi-Chung; Chen, Chao-Hsuan; Yu, Yung‐Lung; Wei, Chyou-Wei

doi:10.1002/fsn3.2298

Cited by 10 publications

(5 citation statements)

References 41 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“… Illustration of the cellular pathways in GBM where vitamin D3 and vitamin E derivatives interact, identified from the systematic literature review of vitamin D3 [ 25 , 26 , 27 , 28 , 29 , 30 ] and vitamin E derivatives [ 31 , 32 , 33 , 34 , 35 ]. (Created with BioRender.com).…”

Section: Resultsmentioning

confidence: 99%

“…However, in the same study, it was shown that, when used independently, γ-Toc increased cell migration, while α-Toc failed to activate the apoptotic pathway in the GBM cells. However, there was a marked increase in cell death and the expression of various apoptotic biomarkers observed in GBM cells exposed to vitamin E and low doses of methotrexate [ 31 ]. In another study, exposure to α-Tocopheryl succinate (TOS), an esterified derivative of α-Toc, induced the chemosensitization of GBM cells to etoposide, triggering a reduction in intracellular glutathione concentration and blockage of multidrug resistance protein 1 (MDP1) [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

“…ATRA also elevated p27 kip1 and decreased CDK2 levels in both cell lines, indicating cell cycle arrest at the G 1 /S phase The combination of ATRA and Interferon-γ control the growth of both GBM cell lines (PTEN-proficient and PTEN-deficient) by inducing cell differentiation, apoptosis, and cell cycle arrest Acidosis induced the self-renewal ability of neurospheres, which were markedly reduced when treated with 10 or 100 nM VD3 under pH 7.4 and pH 6.8 conditions. VD3 inhibited the ATP production of mitochondria and rescued the acidosis triggered ATP enrichment [27] To investigate the effects of 1α, 25 VD3 increased the expression of CYP27B1, 1α25-dihydroxy vitamin D3-24 hydroxylase (CYP24), showing that GBM cell lines were able to metabolize VD3, while it showed no effect on the expression of VDR VD3 metabolites increased the proliferation of GBM cell lines in a dose-dependent manner [31] To investigate the anticancer effects of vitamin C/E and Methotrexate on GBM DBTRG α-Toc 5 µM (24, 48, and 92 h) α-Toc did not reveal any changes in the expression of proteins related to the caspase-3 death pathway (Cleaved PARP, Caspase-3, and Cleaved Caspase-3) on its own in the GBM cell line…”

Section: Retinoids (Vitamin A)mentioning

confidence: 99%

See 2 more Smart Citations

Biomarkers Regulated by Lipid-Soluble Vitamins in Glioblastoma

et al. 2022

View full text Add to dashboard Cite

Glioblastoma (GBM), a highly lethal form of adult malignant gliomas with little clinical advancement, raises the need for alternative therapeutic approaches. Lipid-soluble vitamins have gained attention in malignant brain tumors owing to their pleiotropic properties and their anti-cancer potential have been reported in a number of human GBM cell lines. The aim of this paper is to systematically review and describe the roles of various biomarkers regulated by lipid-soluble vitamins, such as vitamins A, D, E, and K, in the pathophysiology of GBM. Briefly, research articles published between 2005 and 2021 were systematically searched and selected from five databases (Scopus, PubMed, Ovid MEDLINE, EMBASE via Ovid, and Web of Science) based on the study’s inclusion and exclusion criteria. In addition, a number of hand-searched research articles identified from Google Scholar were also included for the analysis. A total of 40 differentially expressed biomarkers were identified from the 19 eligible studies. The results from the analysis suggest that retinoids activate cell differentiation and suppress the biomarkers responsible for stemness in human GBM cells. Vitamin D appears to preferentially modulate several cell cycle biomarkers, while vitamin E derivatives seem to predominantly modulate biomarkers related to apoptosis. However, vitamin K1 did not appear to induce any significant changes to the Raf/MEK/ERK signaling or apoptotic pathways in human GBM cell lines. From the systematic analysis, 12 biomarkers were identified that may be of interest for further studies, as these were modulated by one or two of these lipid-soluble vitamins.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Retinoids (Vitamin A)mentioning

confidence: 99%

See 1 more Smart Citation

Biomarkers Regulated by Lipid-Soluble Vitamins in Glioblastoma

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Nevertheless, the combination of pharmaceutical ascorbate with radiation and temozolomide has the potential to improve the patient's treatment performance and quality of life [ 141 ]. It has been shown by Yiang et al that methotrexate (MTX), a clinical drug for cancer treatment, alone or in combination with vitamins C and E inhibits the growth of GBM cells [ 142 ]. Vitamin C appears to regulate JAK/STAT, TRAIL, TGF/SMAD, and microRNAs in different cancers according to scattered scientific evidence [ 143 ].…”

Section: Some Other Kinds Of Natural Products or Diets Which Might Be...mentioning

confidence: 99%

The Role of Natural Products as Inhibitors of JAK/STAT Signaling Pathways in Glioblastoma Treatment

Fahmideh

Shapourian

Molatefi

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

The permeability of glioblastoma, as well as its escaping the immune system, makes them one of the most deadly human malignancies. By avoiding programmed cell death (apoptosis), unlimited cell growth and metastatic ability could dramatically affect the immune system. Genetic mutations, epigenetic changes, and overexpression of oncogenes can cause this process. On the other hand, the blood-brain barrier (BBB) and intratumor heterogeneity are important factors causing resistance to therapy. Several signaling pathways have been identified in this field, including the Janus tyrosine kinase (JAK) converter and signal transducer and activator of transcription (STAT) activator pathways, which are closely related. In addition, the JAK/STAT signaling pathway contributes to a wide array of tumorigenesis functions, including replication, anti-apoptosis, angiogenesis, and immune suppression. Introducing this pathway as the main tumorigenesis and treatment resistance center can give a better understanding of how it operates. In light of this, it is an important goal in treating many disorders, particularly cancer. The inhibition of this signaling pathway is being considered an approach to the treatment of glioblastoma. The use of natural products alternatively to conventional therapies is another area of research interest among researchers. Some natural products that originate from plants or natural sources can interfere with JAK/STAT signaling in human malignant cells, also by stopping the progression and phosphorylation of JAK/STAT, inducing apoptosis, and stopping the cell cycle. Natural products are a viable alternative to conventional chemotherapy because of their cost-effectiveness, wide availability, and almost no side effects.

show abstract

“…Various preclinical studies conducted over the past few years have found that high dosages of vitamin C could act as an adjuvant prooxidative agent, primarily in chemotherapy and/or radiotherapy of glioblastoma cells [78,82,84,86]. Vitamin C has been found to enhance the chemotherapeutic effects of methotrexate on glioblastoma cells [87]. According to a case study, a 55-year-old woman with GBM who received both radiotherapy and chemotherapy was given vitamin C infusions (85 g/infusion) 2-3 times/week along with a vitamin C supplement (1 g) before each treatment; this not only improved her quality of life but also halted the progression of her disease [88].…”

Section: Vitamin Cmentioning

confidence: 99%

Antioxidants in brain tumors: current therapeutic significance and future prospects

Jha

et al. 2022

Mol Cancer

View full text Add to dashboard Cite

Brain cancer is regarded among the deadliest forms of cancer worldwide. The distinct tumor microenvironment and inherent characteristics of brain tumor cells virtually render them resistant to the majority of conventional and advanced therapies. Oxidative stress (OS) is a key disruptor of normal brain homeostasis and is involved in carcinogenesis of different forms of brain cancers. Thus, antioxidants may inhibit tumorigenesis by preventing OS induced by various oncogenic factors. Antioxidants are hypothesized to inhibit cancer initiation by endorsing DNA repair and suppressing cancer progression by creating an energy crisis for preneoplastic cells, resulting in antiproliferative effects. These effects are referred to as chemopreventive effects mediated by an antioxidant mechanism. In addition, antioxidants minimize chemotherapy-induced nonspecific organ toxicity and prolong survival. Antioxidants also support the prooxidant chemistry that demonstrate chemotherapeutic potential, particularly at high or pharmacological doses and trigger OS by promoting free radical production, which is essential for activating cell death pathways. A growing body of evidence also revealed the roles of exogenous antioxidants as adjuvants and their ability to reverse chemoresistance. In this review, we explain the influences of different exogenous and endogenous antioxidants on brain cancers with reference to their chemopreventive and chemotherapeutic roles. The role of antioxidants on metabolic reprogramming and their influence on downstream signaling events induced by tumor suppressor gene mutations are critically discussed. Finally, the review hypothesized that both pro- and antioxidant roles are involved in the anticancer mechanisms of the antioxidant molecules by killing neoplastic cells and inhibiting tumor recurrence followed by conventional cancer treatments. The requirements of pro- and antioxidant effects of exogenous antioxidants in brain tumor treatment under different conditions are critically discussed along with the reasons behind the conflicting outcomes in different reports. Finally, we also mention the influencing factors that regulate the pharmacology of the exogenous antioxidants in brain cancer treatment. In conclusion, to achieve consistent clinical outcomes with antioxidant treatments in brain cancers, rigorous mechanistic studies are required with respect to the types, forms, and stages of brain tumors. The concomitant treatment regimens also need adequate consideration.

show abstract

Antioxidant vitamins promote anticancer effects on low‐concentration methotrexate‐treated glioblastoma cells via enhancing the caspase‐3 death pathway

Cited by 10 publications

References 41 publications

Biomarkers Regulated by Lipid-Soluble Vitamins in Glioblastoma

Biomarkers Regulated by Lipid-Soluble Vitamins in Glioblastoma

The Role of Natural Products as Inhibitors of JAK/STAT Signaling Pathways in Glioblastoma Treatment

Antioxidants in brain tumors: current therapeutic significance and future prospects

Contact Info

Product

Resources

About