Cancer remains one of the most feared and dreaded diseases in this era of modern medicine, claiming the lives of many, and affecting the quality of life of several others around the globe despite major advances in the diagnosis, treatment, palliative care and the immense resources invested into cancer research. While research in cancer has largely focused on the neoplasm/tumor and the cancerous cells that make up the tumor, more recently, the existence, proliferation, differentiation, migration and invasion of cancer stem cells (CSCs) and the role that CSCs play in tumor initiation, progression, metastasis, drug resistance and relapse/recurrence of the disease has gained widespread interest in cancer research. Although the conventional therapeutic approaches such as surgery, chemotherapy and radiation therapy are effective cancer treatments, very often these treatment modalities fail to target the CSCs, which then later become the source of disease recurrence. A majority of the anti-cancer agents target rapidly dividing cancer cells and normal cells and hence, have side effects that are not expected. Targeting CSCs remains a challenge due to their deviant nature with a low proliferation rate and increased drug resistance mechanism. Ascorbic acid/Vitamin C (Vit.C), a potent antioxidant, is a cofactor for several biosynthetic and gene regulatory enzymes and a vital contributor to immune defense of the body, and was found to be deficient in patients with advanced stages of cancer. Vit.C has gained importance in the treatment of cancer due to its ability to modulate the redox status of the cell and influence epigenetic modifications and significant roles in HIF1α signaling. Studies have reported that intravenous administration of Vit.C at pharmacological doses selectively kills tumor cells and targets CSCs when administered along with chemotherapeutic drugs. In the current article, we provide an in-depth review of how Vit.C plays an important role in targeting CSCs and its possible use as an adjuvant, neoadjuvant or co-treatment in the treatment of cancers.

Neuroblastoma is the second most common paediatric cancer. It developsfrom undifferentiated simpatico-adrenal lineage cells and is mostly sporadic; however, theaetiology behind the development of neuroblastoma is still not fully understood. Intracellularcalcium ([Ca2+]i) is a secondary messenger which regulates numerous cellular processesand, therefore, its concentration is tightly regulated. This review focuses on the role of[Ca2+]i in differentiation, apoptosis and proliferation in neuroblastoma. It describes themechanisms by which [Ca2+]i is regulated and how it modulates intracellular pathways.Furthermore, the importance of [Ca2+]i for the function of anti-cancer drugs is illuminatedin this review as [Ca2+]i could be a target to improve the outcome of anti-cancer treatmentin neuroblastoma. Overall, modulations of [Ca2+]i could be a key target to induce apoptosisin cancer cells leading to a more efficient and effective treatment of neuroblastoma.

Metformin, the most widely used anti-diabetic drug, also exhibits anti-cancer properties; however, the true potential of metformin as an anticancer drug remains largely unknown. In this study using mouse microvascular endothelial cells (MMECs), we investigated the effects of metformin alone or in combination with the glycolytic inhibitor, 2-deoxyglucose (2DG), on angiogenesis-a process known to be an integral part of tumor growth, cancer cell survival and metastasis. MMECs were exposed to 2DG (1–10 mM) for 48 h in the absence or presence of metformin (2 mM). The status of angiogenic and anti-angiogenic marker proteins, proteins of the mTOR pathway and cell-cycle-related proteins were quantified by Western blot analysis. Assays for cell proliferation, migration and tubulogenesis were also performed. We observed robust up-regulation of anti-angiogenic thrombospondin-1 (TSP1) and increased TSP1-CD36 co-localization with a marked decrease in the levels of phosphorylated vascular endothelial growth factor receptor-2 (pVEGFR2; Y1175) in 2DG (5 mM) exposed cells treated with metformin (2 mM). Additionally, treatment with metformin and 2DG (5 mM) inhibited the Akt/mTOR pathway and down-regulated the cell-cycle-related proteins such as p-cyclin B1 (S147) and cyclins D1 and D2 when compared to cells that were treated with either 2DG or metformin alone. Treatment with a combination of 2DG (5 mM) and metformin (2 mM) also significantly decreased cell proliferation, migration and tubulogenic capacity when compared to cells that were treated with either 2DG or metformin alone. The up-regulation of TSP1, inhibition of cell proliferation, migration and tubulogenesis provides support to the argument that the combination of metformin and 2DG may prove to be an appropriate anti-proliferative and anti-angiogenic therapeutic strategy for the treatment of some cancers.

Coronavirus 2019 (COVID-19) is an infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the lungs. COVID-19 symptoms include the presence of fevers, dry coughs, fatigue, sore throat, headaches, diarrhea, and a loss of taste or smell. However, it is understood that SARS-CoV-2 is neurotoxic and neuro-invasive and could enter the central nervous system (CNS) via the hematogenous route or via the peripheral nerve route and causes encephalitis, encephalopathy, and acute disseminated encephalomyelitis (ADEM) in COVID-19 patients. This review discusses the possibility of SARS-CoV-2-mediated Multiple Sclerosis (MS) development in the future, comparable to the surge in Parkinson’s disease cases following the Spanish Flu in 1918. Moreover, the SARS-CoV-2 infection is associated with a cytokine storm. This review highlights the impact of these modulated cytokines on glial cell interactions within the CNS and their role in potentially prompting MS development as a secondary disease by SARS-CoV-2. SARS-CoV-2 is neurotropic and could interfere with various functions of neurons leading to MS development. The influence of neuroinflammation, microglia phagocytotic capabilities, as well as hypoxia-mediated mitochondrial dysfunction and neurodegeneration, are mechanisms that may ultimately trigger MS development.