Gold Nanoparticles in Triple-Negative Breast Cancer Therapeutics.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer with enhanced metastasis and poor survival. Though chemotherapy, radiotherapy, photothermal therapy (PTT), photodynamic therapy (PDT), and gene delivery are used to treat TNBC, various side effects limit these therapeutics against TNBC. In this review article, we have focused on the mechanism of action of gold nanoparticles (AuNPs) to enhance the efficacy of therapeutics with targeted delivery on TNBC cells. METHODS: Research data were accumulated from PubMed, Scopus, Web of Science, and Google Scholar using searching criteria "gold nanoparticles and triple-negative breast cancer" and "gold nanoparticles and cancer". Though we reviewed many old papers, the most cited papers were from the last ten years. RESULTS: Various studies indicate that AuNPs can enhance bioavailability, site-specific drug delivery, and efficacy of chemotherapy, radiotherapy, PTT, and PDT as well as modulate gene expression. The role of AuNPs in the modulation of TNBC therapeutics through the inhibition of cell proliferation, progression, and metastasis has been proved in vitro and in vivo studies. As these mechanistic actions of AuNPs are most desirable to develop drugs with enhanced therapeutic efficacy against TNBC, it might be a promising approach to apply AuNPs for TNBC therapeutics. CONCLUSION: This article reviewed the mechanism of action of AuNPs and their application in the enhancement of therapeutics against TNBC. Much more attention is required for studying the role of AuNPs in developing them either as a single or synergistic anticancer agent against TNBC.

Current Landscape of Therapeutic Resistance in Lung Cancer and Promising Strategies to Overcome Resistance.

Lung cancer is one of the leading causes of cancer-related deaths worldwide with a 5-year survival rate of less than 18%. Current treatment modalities include surgery, chemotherapy, radiation therapy, targeted therapy, and immunotherapy. Despite advances in therapeutic options, resistance to therapy remains a major obstacle to the effectiveness of long-term treatment, eventually leading to therapeutic insensitivity, poor progression-free survival, and disease relapse. Resistance mechanisms stem from genetic mutations and/or epigenetic changes, unregulated drug efflux, tumor hypoxia, alterations in the tumor microenvironment, and several other cellular and molecular alterations. A better understanding of these mechanisms is crucial for targeting factors involved in therapeutic resistance, establishing novel antitumor targets, and developing therapeutic strategies to resensitize cancer cells towards treatment. In this review, we summarize diverse mechanisms driving resistance to chemotherapy, radiotherapy, targeted therapy, and immunotherapy, and promising strategies to help overcome this therapeutic resistance.

The promise of targeting heme and mitochondrial respiration in normalizing tumor microenvironment and potentiating immunotherapy.

Cancer immunotherapy shows durable treatment responses and therapeutic benefits compared to other cancer treatment modalities, but many cancer patients display primary and acquired resistance to immunotherapeutics. Immunosuppressive tumor microenvironment (TME) is a major barrier to cancer immunotherapy. Notably, cancer cells depend on high mitochondrial bioenergetics accompanied with the supply of heme for their growth, proliferation, progression, and metastasis. This excessive mitochondrial respiration increases tumor cells oxygen consumption, which triggers hypoxia and irregular blood vessels formation in various regions of TME, resulting in an immunosuppressive TME, evasion of anti-tumor immunity, and resistance to immunotherapeutic agents. In this review, we discuss the role of heme, heme catabolism, and mitochondrial respiration on mediating immunosuppressive TME by promoting hypoxia, angiogenesis, and leaky tumor vasculature. Moreover, we discuss the therapeutic prospects of targeting heme and mitochondrial respiration in alleviating tumor hypoxia, normalizing tumor vasculature, and TME to restore anti-tumor immunity and resensitize cancer cells to immunotherapy.

Targeting Inflammatory Mediators: An Anticancer Mechanism of Thymoquinone Action.

BACKGROUND: Thymoquinone is a promising anticancer molecule, the chemopreventive role of which is well-known at least in vitro and in the animal model. In this review article, we focused on the anti-inflammatory activities of thymoquinone in cancer cells. METHOD: Research data on inflammation, cancer and thymoquinone were acquired from PubMed, Scopus, Web of Science and Google Scholar. We reviewed papers published since the mid of the last century, and the most cited papers of the last ten years. RESULTS: Studies indicate that thymoquinone possesses immunomodulatory activities, in addition to its chemopreventive role, as thymoquinone can target and modulate inflammatory molecules, like nuclear factor kappa B (NF-κß), interleukins, tumor necrosis factor-α (TNF-α), and certain growth factors. As chronic inflammation plays an important role in cancer development, controlling inflammatory pathways is an important mechanism of an anticancer molecule, and modulation of inflammatory pathways might be one of the key mechanisms of thymoquinone's anticancer activities. CONCLUSION: This article reviewed the role of inflammation on cancer development, and the action of thymoquinone on inflammatory molecules, which have been proved in vitro and in vivo. Much attention is required for studying the role of thymoquinone in immunotherapeutics and developing this molecule as a future anticancer drug.

Thymoquinone in autoimmune diseases: Therapeutic potential and molecular mechanisms.

Autoimmune diseases (AUDs) are a multifactorial disease, among which rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis are more prevalent. Several anti-inflammatory, biologics, and AUD-modifying drugs are found effective against them, but their repeated use are associated with various adverse effects. In this review article, we have focused on the regulation of inflammatory molecules, molecular signaling pathways, immune cells, and epigenetics by natural product thymoquinone on AUDs. Studies indicate that thymoquinone can regulate inflammatory molecules including interferons, interleukins, tumor necrosis factor-α (TNF-α), oxidative stress, regulatory T cells, and various signaling pathways such as nuclear factor kappa beta (NF-κß), janus kinase/signal transduction and activator of transcription (JAK-STAT), mitogen-activated protein kinase (MAPK) at the molecular level and epigenetic alteration. As these molecules and signaling pathways with defective immune function play an important role in AUD development, controlling these molecules and deregulated molecular mechanism is a significant feature of AUD therapeutics. Interestingly thymoquinone is reported to possess all these potential. This article reviewed the deregulated mechanism of AUDs, and the action of thymoquinone on inflammatory molecules, immune cells, signaling pathways, and epigenetic machinery. Thymoquinone can be regarded as a potential drug candidate for AUD treatment.

Current Landscape of Natural Products against Coronaviruses: Perspectives in COVID-19 Treatment and Anti-viral Mechanism.

BACKGROUND: SARS-CoV-2 is a coronavirus, and the infection by SARS-CoV-2, termed as COVID-19, was first reported in Wuhan, China, at the end of 2019, and this outbreak became a pandemic in February of 2020. Till now, there is no effective drug or vaccine against this virus that can make a complete cure; however, a number of drugs are in trials. OBJECTIVES: In this review, we have focused on an alternative therapeutic approach using natural products utilizing the host anti-viral responses for resolving COVID-19 pathogenesis. METHODS: We have searched databases like PubMed, Scopus, Web of Science, and Google Scholar for articles related to natural products and viral diseases, with a specific focus on coronaviruses, as well as other RNA viruses and recent updates on the COVID-19 pandemic, and collected articles and reviewed them comprehensively. RESULTS: Scientific studies clarified the viral pathogenesis that involved viral entrance into host cells and anti-viral response inside the cells, which can be effectively targeted by numerous natural compounds from different sources. Many of these compounds can potentially target viral genomic material or protein machinery. Natural products that were found effective against other coronaviruses, especially SARS-CoV or MERS-CoV (which emerged in 2002 and 2012, respectively), might be effective against SARS-CoV-2 due to their structural similarities. CONCLUSION: COVID-19 pandemic is a global emergency thus, urgent drug development is necessary. Natural products can be the biggest source of drugs, as they have been found to be effective in other coronaviruses previously; however, time is required to establish the clinical success of these drugs for clinical applications.