SGLT2 Inhibitors as Potential Anticancer Agents.

Sodium-glucose cotransporter 2 (SGLT2) serves as a critical glucose transporter that has been reported to be overexpressed in cancer models, followed by increased glucose uptake in both mice and humans. Inhibition of its expression can robustly thwart tumor development in vitro and in vivo. SGLT2 inhibitors are a comparatively new class of antidiabetic drugs that have demonstrated anticancer effects in several malignancies, including breast, liver, pancreatic, thyroid, prostate, and lung cancers.

Preclinical and Clinical Research Models of Prostate Cancer: A Brief Overview.

The incidence and mortality from prostate cancer (PCa) are on the rise which poses a major public health concern worldwide. In this narrative review, we have summarized the characteristics of major in vitro and in vivo PCa models including their utility in developing treatment strategies. Androgens, particularly, testosterone and dihydrotestosterone (DHT) activate the androgen receptor (AR) signaling pathway that facilitates the development and progression of castration resistant PCa.

Therapeutic promise of carotenoids as antioxidants and anti-inflammatory agents in neurodegenerative disorders.

Neurodegenerative disorders (NDs) including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis have various disease-specific causal factors and pathological features. A very common characteristic of NDs is oxidative stress (OS), which takes place due to the elevated generation of reactive oxygen species during the progression of NDs. Furthermore, the pathological condition of NDs including an increased level of protein aggregates can further lead to chronic inflammation because of the microglial activation.

Comparison of Anticancer Drug Toxicities: Paradigm Shift in Adverse Effect Profile.

The inception of cancer treatment with chemotherapeutics began in the 1940s with nitrogen mustards that were initially employed as weapons in World War II. Since then, treatment options for different malignancies have evolved over the period of last seventy years. Until the late 1990s, all the chemotherapeutic agents were small molecule chemicals with a highly nonspecific and severe toxicity spectrum.

Sensitivity of SARS-CoV-2 towards Alcohols: Potential for Alcohol-Related Toxicity in Humans.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative organism that is highly contagious and has been responsible for more than 240 million cases and 5 million deaths worldwide. Using masks, soap-based hand washing, and maintaining social distancing are some of the common methods to prevent the spread of the virus. In the absence of any preventive medications, from the outset of pandemic, alcohol-based hand sanitizers (ABHS) have been one of the first-line measures to control transmission of Coronavirus Disease 2019 (COVID-19).

The Role of Oxidative Stress and Its Counteractive Utility in Colorectal Cancer (CRC).

An altered redox status accompanied by an elevated generation of reactive oxygen/nitrogen species (ROS/RNS) has been implicated in a number of diseases including colorectal cancer (CRC). CRC, being one of the most common cancers worldwide, has been reported to be associated with multiple environmental and lifestyle factors (e.g.

Potential Application of Ionic Liquids in Pharmaceutical Dosage Forms for Small Molecule Drug and Vaccine Delivery System.

Ionic liquids are salts in which the ions are poorly coordinated, which causes them to exist in liquid form below 100°C, or at room temperature. Therefore, these are also defined as room temperature ionic liquids (RTILs). In ionic liquids, at least one ion has a delocalized charge and one component is organic, which prevents the formation of a stable solid form of crystal lattice.

Thymoquinone as a Potential Adjuvant Therapy for Cancer Treatment: Evidence from Preclinical Studies.

Thymoquinone (TQ), the main bioactive component of Nigella sativa, has been found to exhibit anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteracts carcinogenesis, malignant growth, invasion, migration, and angiogenesis. Moreover, TQ can specifically sensitize tumor cells toward conventional cancer treatments (e.

New insights into estrogenic regulation of -methylguanine DNA-methyltransferase (MGMT) in human breast cancer cells: Co-degradation of ER-α and MGMT proteins by fulvestrant or -benzylguanine indicates fresh avenues for therapy.

Endocrine therapy using estrogen receptor-α (ER-α) antagonists for attenuating horm2one-driven cell proliferation is a major treatment modality for breast cancers. To exploit any DNA repair deficiencies associated with endocrine therapy, we investigated the functional and physical interactions of ER-α with -methylguanine DNA methyltransferase (MGMT), a unique DNA repair protein that confers tumor resistance to various anticancer alkylating agents. The ER-α -positive breast cancer cell lines (MCF-7, T47D) and ER- negative cell lines (MDAMB-468, MDAMB-231), and established inhibitors of ER-α and MGMT, namely, ICI-182,780 (Faslodex) and O-benzylguanine, respectively, were used to study MGMT- ER interactions.

Potent anti-proliferative actions of a non-diuretic glucosamine derivative of ethacrynic acid.

Ethacrynic acid (EA), a known inhibitor of the neoplastic marker glutathione S-transferase P1 and other GSTs, exerts a weak antiproliferative activity against human cancer cells. The clinical use of EA (Edecrin) as an anticancer drug is limited by its potent loop diuretic activity. In this study, we developed a non-diuretic 2-amino-2-deoxy-d-glucose conjugated EA (EAG) to target tumors cells via the highly expressed glucose transporter 1 (GLUT1).

Piperlongumine exerts cytotoxic effects against cancer cells with mutant p53 proteins at least in part by restoring the biological functions of the tumor suppressor.

Piperlongumine (PL), a small molecule alkaloid present in black pepper (Piper longum), has been reported to kill tumor cells irrespective of their p53 gene status, however, the mechanisms involved are unknown. Since p53 is a redox-sensitive protein, we hypothesized that the redox imbalance induced by PL may affect the structure and/or function of the mutant p53 protein and promote cell death. We used two human colon cancer cell lines, the HT29 and SW620 which harbor the R273H DNA contact abrogatory mutation in p53.

Posttranslational Regulation of O(6)-Methylguanine-DNA Methyltransferase (MGMT) and New Opportunities for Treatment of Brain Cancers.

O(6)-Methylguanine-DNA-methyltransferase (MGMT) is an antimutagenic DNA repair protein highly expressed in human brain tumors. Because MGMT repairs the mutagenic, carcinogenic and cytotoxic O(6)-alkylguanine adducts, including those generated by the clinically used anticancer alkylating agents, it has emerged as a central and rational target for overcoming tumor resistance to alkylating agents. Although the pseudosubstrates for MGMT [O(6)-benzylguanine, O(6)-(4- bromothenyl)guanine] have gained attention as powerful and clinically-relevant inhibitors, bone marrow suppression due to excessive alkylation damage has diminished this strategy.

Evaluation of internal and marginal fit of two metal ceramic system - in vitro study.

Introduction: The high strength porcelain fused metal crowns have been extensively used in dentistry. However, the fit is the most encountered problems in porcelain fused metal crowns. This mainly depends on the fabrication technique.