Reactive oxygen species (ROS) induce carcinogenesis by causing genetic mutations, activating oncogenes, and increasing oxidative stress, all of which affect cell proliferation, survival, and apoptosis. When compared to normal cells, cancer cells have higher levels of ROS, and they are responsible for the maintenance of the cancer phenotype; this unique feature in cancer cells may, therefore, be exploited for targeted therapy. Quercetin (QC), a plant-derived bioflavonoid, is known for its ROS scavenging properties and was recently discovered to have various antitumor properties in a variety of solid tumors. Adaptive stress responses may be induced by persistent ROS stress, allowing cancer cells to survive with high levels of ROS while maintaining cellular viability. However, large amounts of ROS make cancer cells extremely susceptible to quercetin, one of the most available dietary flavonoids. Because of the molecular and metabolic distinctions between malignant and normal cells, targeting ROS metabolism might help overcome medication resistance and achieve therapeutic selectivity while having little or no effect on normal cells. The powerful bioactivity and modulatory role of quercetin has prompted extensive research into the chemical, which has identified a number of pathways that potentially work together to prevent cancer, alongside, QC has a great number of evidences to use as a therapeutic agent in cancer stem cells. This current study has broadly demonstrated the function-mechanistic relationship of quercetin and how it regulates ROS generation to kill cancer and cancer stem cells. Here, we have revealed the regulation and production of ROS in normal cells and cancer cells with a certain signaling mechanism. We demonstrated the specific molecular mechanisms of quercetin including MAPK/ERK1/2, p53, JAK/STAT and TRAIL, AMPKα1/ASK1/p38, RAGE/PI3K/AKT/mTOR axis, HMGB1 and NF-κB, Nrf2-induced signaling pathways and certain cell cycle arrest in cancer cell death, and how they regulate the specific cancer signaling pathways as long-searched cancer therapeutics.

Despite significant therapeutic advancements for cancer, an atrocious global burden (for example, health and economic) and radio- and chemo-resistance limit their effectiveness and result in unfavorable health consequences. Natural compounds are generally considered safer than synthetic drugs, and their use in cancer treatment alone, or in combination with conventional therapies, is increasingly becoming accepted. Interesting outcomes from pre-clinical trials using Baicalein in combination with conventional medicines have been reported, and some of them have also undergone clinical trials in later stages. As a result, we investigated the prospects of Baicalein, a naturally occurring substance extracted from the stems of Scutellaria baicalensis Georgi and Oroxylum indicum Kurz, which targets a wide range of molecular changes that are involved in cancer development. In other words, this review is primarily driven by the findings from studies of Baicalein therapy in several cancer cell populations based on promising pre-clinical research. The modifications of numerous signal transduction mechanisms and transcriptional agents have been highlighted as the major players for Baicalein’s anti-malignant properties at the micro level. These include AKT serine/threonine protein kinase B (AKT) as well as PI3K/Akt/mTOR, matrix metalloproteinases-2 & 9 (MMP-2 & 9), Wnt/-catenin, Poly(ADP-ribose) polymerase (PARP), Mitogen-activated protein kinase (MAPK), NF-κB, Caspase-3/8/9, Smad4, Notch 1/Hes, Signal transducer and activator of transcription 3 (STAT3), Nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein-1 (Keap 1), Adenosine monophosphate-activated protein kinase (AMPK), Src/Id1, ROS signaling, miR 183/ezrin, and Sonic hedgehog (Shh) signaling cascades. The promise of Baicalein as an anti-inflammatory to anti-apoptotic/anti-angiogenic/anti-metastatic medicinal element for treating various malignancies and its capability to inhibit malignant stem cells, evidence of synergistic effects, and design of nanomedicine-based drugs are altogether well supported by the data presented in this review study.

Breast cancer (BC) is one of the most common malignancies in women. Although widespread successful synthetic drugs are available, natural compounds can also be considered as significant anticancer agents for treating BC. Some natural compounds have similar effects as synthetic drugs with fewer side effects on normal cells. Therefore, we aimed to unravel and analyze several molecular mechanisms of genistein (GNT) against BC. GNT is a type of dietary phytoestrogen included in the flavonoid group with a similar structure to estrogen that might provide a strong alternative and complementary medicine to existing chemotherapeutic drugs. Previous research reported that GNT could target the estrogen receptor (ER) human epidermal growth factor receptor-2 (HER2) and several signaling molecules against multiple BC cell lines and sensitize cancer cell lines to this compound when used at an optimal inhibitory concentration. More specifically, GNT mediates the anticancer mechanism through apoptosis induction, arresting the cell cycle, inhibiting angiogenesis and metastasis, mammosphere formation, and targeting and suppressing tumor growth factors. Furthermore, it acts via upregulating tumor suppressor genes and downregulating oncogenes in vitro and animal model studies. In addition, this phytochemical synergistically reverses the resistance mechanism of standard chemotherapeutic drugs, increasing their efficacy against BC. Overall, in this review, we discuss several molecular interactions of GNT with numerous cellular targets in the BC model and show its anticancer activities alone and synergistically. We conclude that GNT can have favorable therapeutic advantages when standard drugs are not available in the pharma markets.

With high inflammatory states from both COVID-19 and HIV conditions further result in complications. The ongoing confrontation between these two viral infections can be avoided by adopting suitable management measures. The aim of this study was to figure out the pharmacological mechanism behind apigenin's role in the synergetic effects of COVID-19 to the progression of HIV patients. We employed computer-aided methods to uncover similar biological targets and signaling pathways associated with COVID-19 and HIV, along with bioinformatics and network pharmacology techniques to assess the synergetic effects of apigenin on COVID-19 to the progression of HIV, as well as pharmacokinetics analysis to examine apigenin's safety in the human body. Stress-responsive, membrane receptor, and induction pathways were mostly involved in gene ontology (GO) pathways, whereas apoptosis and inflammatory pathways were significantly associated in the Kyoto encyclopedia of genes and genomes (KEGG). The top 20 hub genes were detected utilizing the shortest path ranked by degree method and protein-protein interaction (PPI), as well as molecular docking and molecular dynamics simulation were performed, revealing apigenin's strong interaction with hub proteins (MAPK3, RELA, MAPK1, EP300, and AKT1). Moreover, the pharmacokinetic features of apigenin revealed that it is an effective therapeutic agent with minimal adverse effects, for instance, hepatoxicity. Synergetic effects of COVID-19 on the progression of HIV may still be a danger to global public health. Consequently, advanced solutions are required to give valid information regarding apigenin as a suitable therapeutic agent for the management of COVID-19 and HIV synergetic effects. However, the findings have yet to be confirmed in patients, suggesting more in vitro and in vivo studies.