In recent years, the idea that Vitamin C (Vit-C) could be utilized as a form of anti-cancer therapy has generated many contradictory arguments. Recent insights into the physiological characteristics of Vit-C, its pharmacokinetics, and results from preclinical reports, however, suggest that high-dose Vit-C could be effectively utilized in the management of various tumor types. Studies have shown that the pharmacological action of Vit-C can attack various processes that cancerous cells use for their growth and development. Here, we discuss the anti-cancer functions of Vit-C, but also the potential for the use of Vit-C as an epigenetic regulator and immunotherapy enhancer. We also provide a short overview of the current state of systems for scavenging reactive oxygen species (ROS), especially in the context of their influencing high-dose Vit-C toxicity for the inhibition of cancer growth. Even though the mechanisms of Vit-C action are promising, they need to be supported with robust randomized and controlled clinical trials. Moreover, upcoming studies should focus on how to define the most suitable cancer patient populations for high-dose Vit-C treatments and develop effective strategies that combine Vit-C with various concurrent cancer treatment regimens.

Breast cancer (BC) is the most common cancer type among women with a distinct clinical presentation, but the survival rate remains moderate despite advances in multimodal therapy. Consequently, a deeper understanding of the molecular etiology is required for the development of more effective treatments for BC. The relationship between inflammation and tumorigenesis is well established, and the activation of the pro-inflammatory transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is frequently identified in BC. Constitutive NF-κB activation is linked to cell survival, metastasis, proliferation, and hormonal, chemo-, and radiotherapy resistance. Moreover, the crosstalk between NF-κB and other transcription factors is well documented. It is reported that vitamin C plays a key role in preventing and treating a number of pathological conditions, including cancer, when administered at remarkably high doses. Indeed, vitamin C can regulate the activation of NF-κB by inhibiting specific NF-κB-dependent genes and multiple stimuli. In this review, we examine the various NF-κB impacts on BC development. We also provide some insight into how the NF-κB network may be targeted as a potential vulnerability by using natural pro-oxidant therapies such as vitamin C.

Background: Glutamate and voltage-gated sodium channels, both have been the target of intense investigation for its involvement in carcinogenesis and progression of malignant disease. Breast cancer with increased level of glutamate often metastasize to other organs (especially bone), whilst re-expression of ‘neonatal’ Nav1.5, nNav1.5 in breast cancer is known to promote cell invasion in vitro, metastasis in vivo and positive lymph node metastasis in patients. Methods: In this study, the role of nNav1.5 in regulating glutamate level in human breast cancer cells was examined using pharmacological approach (VGSCs specific blocker, TTX, glutamate release inhibitor, riluzole and siRNA-nNav1.5). Effect of these agents were evaluated based on endogenous and exogenous glutamate concentration using glutamate fluorometric assay, mRNA expression of nNav1.5 using qPCR and finally, invasion using 3D culture assay. Results: Endogenous and exogenous glutamate levels were significantly higher in aggressive human breast cancer cells, MDA-MB-231 cells compared to less aggressive human breast cancer cells, MCF-7 and non-cancerous human breast epithelial cells, MCF-10A. Treatment with TTX to MDA-MB-231 cells resulted in significant reduction of endogenous and exogenous glutamate levels corresponded with significant suppression of cell invasion. Subsequently, downregulation of nNav1.5 gene was observed in TTX-treated cells. Conclusions: An interesting link between nNav1.5 expression and glutamate level in aggressive breast cancer cells was detected and requires further investigation.

Aggressive tissue biopsy is commonly unavoidable in the management of most suspected tumor cases to conclusively verify the presence of cancerous cells through histological assessment. The extracted tissue is also immunostained for detection of antigens (tissue tumor markers) of potential prognostic or therapeutic importance to assist in treatment decision. Although liquid biopsies can be a powerful tool for monitoring treatment response, they are still excluded from standard cancer diagnostics, and their utility is still being debated in the scientific community. With a myriad of soluble tissue tumor markers now being discovered, liquid biopsies could completely change the current paradigms of cancer management. Recently, soluble programmed cell death ligand-1 (sPD-L1), which is found in the peripheral blood, i.e. serum and plasma, has shown potential as a pre-therapeutic predictive marker as well as a prognostic biomarker to monitor treatment efficacy. Thus, this review focuses on the emergence of sPD-L1 and promising technologies for its detection in order to support liquid biopsies for future cancer management. FullText for HTML: https://doi.org/10.1093/abbs/gmab077

Nav1.5 and nNav1.5 are potent metastatic markers for breast cancer with aggressive phenotype; detected in tumour tissues positive for lymph node metastasis. In vitro, most of the studies involving Nav1.5 and nNav1.5 were evaluated in monolayer cultured cells. Subsequently, since 3D-spheroid culture is now known for its ability to mimic multiple in vivo tumour microenvironment, there is a need to re-evaluate the potential role of Nav1.5 and nNav1.5 in a reliable tumour-accurate model. This study aimed to develop MDA-MB-231-3D-spheroid culture and assess the mRNA gene expression of Nav1.5 and nNav1.5 including several other potent markers for aggressive breast cancer, MMP1, MMP13 and fibronectin. MDA-MB-231-3D-spheroids were cultured using scaffold-free liquid overlay method (via agarose layered 96-well flat bottomed plate) for 15 days. The total RNA was conventionally extracted and converted to cDNA. The mRNA expression for Nav1.5 and nNav1.5, MMP1, MMP13 and fibronectin were measured using real-time PCR and the expression were analysed via the 2^-ΔΔCt method in which the monolayer culture was used as a normalizing control. MDA-MB-231-3D-spheroid was successfully developed. mRNA expression of Nav1.5, nNav1.5, MMP1 and fibronectin were significantly higher (p < 0.05) in MDA-MB-231-3D-spheroid compared to the monolayer culture; 4.8-fold, 2.1-fold, 62.1-fold and 5.3-fold, respectively. Evaluating the role of tumour markers in a reliable tumour-accurate model is very important. MDA-MB-231-3D-spheroid was able to increase the expression of Nav1.5 and nNav1.5 and can be utilized to re-evaluate the role of Nav1.5 and nNav1.5 in cancer metastasis. Institute for Research in Molecular Medicine, Universiti Sains Malaysia. Universiti Sains Malaysia, FRGS (203/CIPPM/6171212). All authors have declared no conflicts of interest.