Naringenin as potent anticancer phytocompound in breast carcinoma: from mechanistic approach to nanoformulations based therapeutics.

The bioactive compounds present in citrus fruits are gaining broader acceptance in oncology. Numerous studies have deciphered naringenin's antioxidant and anticancer potential in human and animal studies. Naringenin (NGE) potentially suppresses cancer progression, thereby improving the health of cancer patients. The pleiotropic anticancer properties of naringenin include inhibition of the synthesis of growth factors and cytokines, inhibition of the cell cycle, and modification of several cellular signaling pathways. As an herbal remedy, naringenin has significant pharmacological properties, such as anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anti-cancer activities. The inactivation of carcinogens following treatment with pure naringenin, naringenin-loaded nanoparticles, and naringenin combined with anti-cancer agents was demonstrated by data in vitro and in vivo studies. These studies included colon cancer, lung neoplasms, breast cancer, leukemia and lymphoma, pancreatic cancer, prostate tumors, oral squamous cell carcinoma, liver cancer, brain tumors, skin cancer, cervical and ovarian cancers, bladder neoplasms, gastric cancer, and osteosarcoma. The effects of naringenin on processes related to inflammation, apoptosis, proliferation, angiogenesis, metastasis, and invasion in breast cancer are covered in this narrative review, along with its potential to develop novel and secure anticancer medications.

An Updated Review Summarizing the Anticancer Potential of Naringenin.

One important phytochemical is naringenin, which belongs to the flavanone class of polyphenols. It is found in citrus fruits, such as grapefruits, but it can also be found in tomatoes, cherries, and other food-grade medicinal plants. Naringenin has a significant chemotherapeutic promise, as several investigations have conclusively shown. Therefore, the goal of this review is to synthesize the literature that has been done on naringenin as a possible anti-cancer agent and clarify the mechanisms of action that have been described in treatment plans for different kinds of cancer. In a variety of cancer cells, naringenin works by affecting several pathways associated with cell cycle arrest, anti-metastasis, apoptosis, anti-angiogenesis, and DNA repair. It has been shown to alter several molecular targets linked to the development of cancer, such as drug transporters, transcription factors, reactive nitrogen species, reactive oxygen species, cellular kinases, and inflammatory cytokines and regulators of the cell cycle. In summary, this research provides significant insights into the potential of naringenin as a strong and prospective candidate for use in medicines, nutraceuticals, functional foods, and dietary supplements to improve the management of carcinoma.

Unraveling the intricate relationship between lipid metabolism and oncogenic signaling pathways.

Lipids, the primary constituents of the cell membrane, play essential roles in nearly all cellular functions, such as cell-cell recognition, signaling transduction, and energy provision. Lipid metabolism is necessary for the maintenance of life since it regulates the balance between the processes of synthesis and breakdown. Increasing evidence suggests that cancer cells exhibit abnormal lipid metabolism, significantly affecting their malignant characteristics, including self-renewal, differentiation, invasion, metastasis, and drug sensitivity and resistance. Prominent oncogenic signaling pathways that modulate metabolic gene expression and elevate metabolic enzyme activity include phosphoinositide 3-kinase (PI3K)/AKT, MAPK, NF-kB, Wnt, Notch, and Hippo pathway. Conversely, when metabolic processes are not regulated, they can lead to malfunctions in cellular signal transduction pathways. This, in turn, enables uncontrolled cancer cell growth by providing the necessary energy, building blocks, and redox potentials. Therefore, targeting lipid metabolism-associated oncogenic signaling pathways could be an effective therapeutic approach to decrease cancer incidence and promote survival. This review sheds light on the interactions between lipid reprogramming and signaling pathways in cancer. Exploring lipid metabolism as a target could provide a promising approach for creating anticancer treatments by identifying metabolic inhibitors. Additionally, we have also provided an overview of the drugs targeting lipid metabolism in cancer in this review.

Deciphering the Correlation between the Emergence of Lung Carcinoma Associated with Tuberculosis-related Inflammation.

Lung cancer and tuberculosis (TB) are classified as the second-most life-threatening diseases globally. They both are exclusively represented as major public health risks and might exhibit similar symptoms, occasionally diagnosed simultaneously. Several epidemiological studies suggest that TB is a significant risk factor for the progression of lung cancer. The staggering mortality rates of pulmonary disorders are intrinsically connected to lung cancer and TB. Numerous factors play a pivotal role in the development of TB and may promote lung carcinogenesis, particularly among the geriatric population. Understanding the intricacies involved in the association between lung carcinogenesis and TB has become a crucial demand of current research. Consequently, this study aims to comprehensively review current knowledge on the relationship between tuberculosis-related inflammation and the emergence of lung carcinoma, highlighting the impact of persistent inflammation on lung tissue, immune modulation, fibrosis, aspects of reactive oxygen species, and an altered microenvironment that are linked to the progression of tuberculosis and subsequently trigger lung carcinoma.

Ferroptosis targeting natural compounds as a promising approach for developing potent liver cancer agents.

Liver cancer is the second leading cause of cancer-related death worldwide. However, treatment options, including surgical resection, transplantation, and molecular drug therapies, are of limited effectiveness. Recent studies have demonstrated that suppressing ferroptosis might be a pivotal signal for liver cancer initiation, thus providing a new way to combat liver cancer. Ferroptosis is a distinct form of controlled cell death that differs from conventional cell death routes like apoptosis, necrosis, and pyroptosis. It results from intracellular iron overload, which raises iron-dependent reactive oxygen species. This, in turn, leads to the accumulation of lipid peroxides that further result in oxidative damage to cell membranes, disrupt normal functioning, and ultimately speed up the ferroptosis phenomenon. Ferroptosis regulation is intricately linked to cellular physiological processes, encompassing iron metabolism, lipid metabolism, and the equilibrium between oxygen-free radical reactions and lipid peroxidation. This review intends to summarize the natural compounds targeting ferroptosis in liver cancer to offer new therapeutic ideas for liver cancer. Furthermore, it serves as the foundation for identifying and applying chemical medicines and natural chemicals that target ferroptosis to treat liver cancer efficiently.

Review Deciphering the Potential of Nanotherapeutics in Lung Cancer Management.

Lung cancer remains a formidable challenge in oncology, necessitating the develop-ment of more effective prognostic and diagnostic techniques due to inefficient conventional therapeutic approaches and inadequate methods for early lung cancer diagnosis. Despite im-mense progress in the development of innovative strategies to alleviate the impact of this devas-tating disease, the outcomes, unfortunately, remain unsatisfactory, particularly in targeted drug delivery methods. Consequently, nanotechnology has emerged as a revolutionary force in cancer research to develop more effective targeted drug delivery tools due to its extraordinary capacity at the atomic and molecular levels. It has appeared as a beacon of hope in this area of unmet need, providing innovative ways for the prognosis and diagnosis of lung carcinoma. Therefore, this comprehensive review delves into the evolving field of nano-based therapeutics, shedding light on their potential to transform lung cancer treatment. This study meticulously explores the most promising nano-based strategies that have been extensively linked with the treatment of lung carcinoma and mainly emphasizes targeted drug delivery methods and therapies. Addition-ally, this review encapsulates the favorable results of clinical trials, which support the potential pathways for further development of nanotherapeutics in lung cancer management.

Emerging trends of phytochemicals as ferroptosis modulators in cancer therapy.

Ferroptosis, a novel form of regulated cell death characterized by dependence on iron and lipid peroxidation, has been implicated in a wide range of clinical conditions including neurological diseases, cardiovascular disorders, acute kidney failure, and various types of cancer. Therefore, it is critical to suppress cancer progression and proliferation. Ferroptosis can be triggered in cancer cells and some normal cells by synthetic substances, such as erastin, Ras-selective lethal small molecule-3, or clinical pharmaceuticals. Natural bioactive compounds are traditional drug discovery tools, and some have been therapeutically used as dietary additives or pharmaceutical agents against various malignancies. The fact that natural products have multiple targets and minimal side effects has led to notable advances in anticancer research. Research has indicated that ferroptosis can also be induced by natural compounds during cancer treatment. In this review, we focused on the most recent developments in emerging molecular processes and the significance of ferroptosis in cancer. To provide new perspectives on the future development of ferroptosis-related anticancer medications, we also provide a summary of the implications of natural phytochemicals in triggering ferroptosis through ROS production and ferritinophagy induction in a variety of malignancies.

A mechanistic review of the pharmacological potential of narirutin: a dietary flavonoid.

Flavanones, a type of polyphenol, are found in substantial amounts in citrus fruits. When high- or moderate-dose orange juice consumption occurs, flavanones make up a significant portion of the total polyphenols in plasma. Disaccharide derivative narirutin, mainly dihydroxy flavanone, is found in citrus fruits. The substantial chemotherapeutic potential of narirutin has been amply demonstrated by numerous experimental studies. Consequently, the purpose of this study is to compile the research that has already been done showing narirutin to be a promising anticancer drug, with its mechanism of action being documented in treatment plans for various cancer forms. Narirutin functions in a variety of cancer cells by regulating several pathways that include cell cycle arrest, apoptosis, antiangiogenic, antimetastatic, and DNA repair. Narirutin has been shown to modify many molecular targets linked to the development of cancer, including drug transporters, cell cycle mediators, transcription factors, reactive oxygen species, reactive nitrogen species, and inflammatory cytokines. Taken together, these reviews offer important new information about narirutin's potential as a potent and promising drug candidate for use in medicines, functional foods, dietary supplements, nutraceuticals, and other products targeted at improving the treatment of cancer.

Synthesis, in silico screening, and biological evaluation of novel pyridine congeners as anti-epileptic agents targeting AMPA (α-amino-3-hydroxy-5-methylisoxazole) receptors.

The research involves the synthesis of a series of new pyridine analogs 5(i-x) and their evaluation for anti-epileptic potential using in silico and in vivo models. Synthesis of the compounds was accomplished by using the Vilsmeier-Haack reaction principle. AutoDock 4.2 was used for their in silico screening against AMPA (-amino-3-hydroxy-5-methylisoxazole) receptor (PDB ID:3m3f). For in vivo testing, the maximal electroshock seizure (MES) model was used. The physicochemical, pharmacokinetic, drug-like, and drug-score features of all synthesized compounds were assessed using the online Swiss ADME and Protein Plus software. The in silico results showed that all the synthesized compounds 5(i-x) had 1-3 interactions and affinities ranging from -6.5 to -8.0 kJ/mol with the targeted receptor compared to the binding affinities of the standard drug phenytoin and the original ligand of the target (P99), which were -7.6 and -6.8 kJ/mol, respectively. In vivo study results showed that the compound 5-Carbamoyl-2-formyl-1-[2-(4-nitrophenyl)-2-oxo-ethyl]-pyridinium gave 60% protection against epileptic seizures compared to 59% protection afforded by regular phenytoin. All of them met Lipinski's rule of five and had drug-likeness and drug score values of 0.55 and 0.8, respectively, making them chemically and functionally like phenytoin. According to the findings of the studies, the synthesized derivatives have the potential to be employed as a stepping stone in the development of novel anti-epileptic drugs.

Terpenoid-Mediated Targeting of STAT3 Signaling in Cancer: An Overview of Preclinical Studies.

Cancer has become one of the most multifaceted and widespread illnesses affecting human health, causing substantial mortality at an alarming rate. After cardiovascular problems, the condition has a high occurrence rate and ranks second in terms of mortality. The development of new drugs has been facilitated by increased research and a deeper understanding of the mechanisms behind the emergence and advancement of the disease. Numerous preclinical and clinical studies have repeatedly demonstrated the protective effects of natural terpenoids against a range of malignancies. Numerous potential bioactive terpenoids have been investigated in natural sources for their chemopreventive and chemoprotective properties. In practically all body cells, the signaling molecule referred to as signal transducer and activator of transcription 3 (STAT3) is widely expressed. Numerous studies have demonstrated that STAT3 regulates its downstream target genes, including Bcl-2, Bcl-xL, cyclin D1, c-Myc, and survivin, to promote the growth of cells, differentiation, cell cycle progression, angiogenesis, and immune suppression in addition to chemotherapy resistance. Researchers viewed STAT3 as a primary target for cancer therapy because of its crucial involvement in cancer formation. This therapy primarily focuses on directly and indirectly preventing the expression of STAT3 in tumor cells. By explicitly targeting STAT3 in both in vitro and in vivo settings, it has been possible to explain the protective effect of terpenoids against malignant cells. In this study, we provide a complete overview of STAT3 signal transduction processes, the involvement of STAT3 in carcinogenesis, and mechanisms related to STAT3 persistent activation. The article also thoroughly summarizes the inhibition of STAT3 signaling by certain terpenoid phytochemicals, which have demonstrated strong efficacy in several preclinical cancer models.

Review Deciphering the Anticancer Efficacy of Resveratrol and their Associated Mechanisms in Human Carcinoma.

The scientific world has recently shown wider attention to elucidating the anticancerous potential of numerous plant-based bioactive compounds. Many research studies have suggested that consuming foods high in polyphenols, which are present in large amounts in grains, legumes, vegetables, and fruits, may delay the onset of various illnesses, including cancer. Normal cells with genetic abnormalities begin the meticulously organized path leading to cancer, which causes the cells to constantly multiply, colonize, and metastasize to other organs like the liver, lungs, colon, and brain. Resveratrol is a naturally occurring stilbene and non-flavonoid polyphenol, a phytoestrogen with antioxidant, anti-inflammatory, cardioprotective, and anticancer properties. Resveratrol makes cancer cells more susceptible to common chemotherapeutic treatments by reversing multidrug resistance in cancer cells. This is especially true when combined with clinically used medications. Several new resveratrol analogs with enhanced anticancer effectiveness, absorption, and pharmacokinetic profile have been discovered. The present emphasis of this review is the modulation of intracellular molecular targets by resveratrol in vivo and in vitro in various malignancies. This review would help future researchers develop a potent lead candidate for efficiently managing human cancers.

Study Deciphering the Crucial Involvement of Notch Signaling Pathway in Human Cancers.

In recent years, dysregulation of the notch pathway has been associated with the development and progression of various cancers. Notch signaling is involved in several cellular processes such as proliferation, differentiation, apoptosis, and angiogenesis, and its abnormal activation can lead to uncontrolled cell growth and tumorigenesis. In various cancers, the Notch pathway has been shown to have both tumor-promoting and tumor-suppressive effects, depending on the context and stage of cancer development. In some cases, activation of the Notch pathway has been shown to promote tumor growth and progression, while in others it has been shown to inhibit tumor growth and induce cell death. The Notch pathway has been found to be particularly important in the development of leukaemia, breast cancer, lung cancer and pancreatic cancer. In leukaemia, the Notch pathway is often activated, which promotes the survival and proliferation of leukaemia cells. In breast cancer, Notch signaling has been implicated in tumor initiation and maintenance of cancer stem cells. In cervical cancer, the Notch signaling pathway has been shown to play a crucial role in the development of the disease. In lung cancer, Notch activation promotes cancer cell proliferation and migration, while in pancreatic cancer, Notch signaling is associated with tumor initiation and resistance to chemotherapy. Understanding the role of the Notch pathway in cancer development and progression may provide new opportunities for the development of targeted therapies for cancer treatment. Several drugs targeting the Notch pathway are currently in preclinical or clinical development and may hold promise for anticancer therapy in the future.

Reconciling the Gap between Medications and their Potential Leads: The Role of Marine Metabolites in the Discovery of New Anticancer Drugs: A Comprehensive Review.

One-third of people will be diagnosed with cancer at some point in their lives, making it the second leading cause of death globally each year after cardiovascular disease. The complex anticancer molecular mechanisms have been understood clearly with the advent of improved genomic, proteomic, and bioinformatics. Our understanding of the complex interplay between numerous genes and regulatory genetic components within cells explaining how this might lead to malignant phenotypes has greatly expanded. It was discovered that epigenetic resistance and a lack of multitargeting drugs were highlighted as major barriers to cancer treatment, spurring the search for innovative anticancer treatments. It was discovered that epigenetic resistance and a lack of multitargeting drugs were highlighted as major barriers to cancer treatment, spurring the search for innovative anticancer treatments. Many popular anticancer drugs, including irinotecan, vincristine, etoposide, and paclitaxel, have botanical origins. Actinomycin D and mitomycin C come from bacteria, while bleomycin and curacin come from marine creatures. However, there is a lack of research evaluating the potential of algae-based anticancer treatments, especially in terms of their molecular mechanisms. Despite increasing interest in the former, and the promise of the compounds to treat tumours that have been resistant to existing treatment, pharmaceutical development of these compounds has lagged. Thus, the current review focuses on the key algal sources that have been exploited as anticancer therapeutic leads, including their biological origins, phytochemistry, and the challenges involved in converting such leads into effective anticancer drugs.

Insights on the Correlation between Mitochondrial Dysfunction and the Progression of Parkinson's Disease.

The aetiology of a progressive neuronal Parkinson's disease has been discussed in several studies. However, due to the multiple risk factors involved in its development, such as environmental toxicity, parental inheritance, misfolding of protein, ageing, generation of reactive oxygen species, degradation of dopaminergic neurons, formation of neurotoxins, mitochondria dysfunction, and genetic mutations, its mechanism of involvement is still discernible. Therefore, this study aimed to review the processes or systems that are crucially implicated in the conversion of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) into its lethal form, which directly blockades the performance of mitochondria, leading to the formation of oxidative stress in the dopaminergic neurons of substantia nigra pars compacta (SNpc) and resulting in the progression of an incurable Parkinson's disease. This review also comprises an overview of the mutated genes that are frequently associated with mitochondrial dysfunction and the progression of Parkinson's disease. Altogether, this review would help future researchers to develop an efficient therapeutic approach for the management of Parkinson's disease via identifying potent prognostic and diagnostic biomarkers.

Novel Approaches for the Management of Type 2 Diabetes Mellitus: An Update.

Diabetes mellitus is an irreversible, chronic metabolic disorder indicated by hyperglycemia. It is now considered a worldwide pandemic. T2DM, a spectrum of diseases initially caused by tissue insulin resistance and slowly developing to a state characterized by absolute loss of secretory action of the ß cells of the pancreas, is thought to be caused by reduced insulin secretion, resistance to tissue activities of insulin, or a combination of both. Insulin secretagogues, biguanides, insulin sensitizers, alpha-glucosidase inhibitors, incretin mimetics, amylin antagonists, and sodium-glucose co-transporter-2 (SGLT2) inhibitors are the main medications used to treat T2DM. Several of these medication's traditional dosage forms have some disadvantages, including frequent dosing, a brief half-life, and limited absorption. Hence, attempts have been made to develop new drug delivery systems for oral antidiabetics to ameliorate the difficulties associated with conventional dosage forms. In comparison to traditional treatments, this review examines the utilization of various innovative therapies (such as microparticles, nanoparticles, liposomes, niosomes, phytosomes, and transdermal drug delivery systems) to improve the distribution of various oral hypoglycemic medications. In this review, we have also discussed some new promising candidates that have been approved recently by the US Food and Drug Administration for the treatment of T2DM, like semaglutide, tirzepatide, and ertugliflozin. They are used as a single therapy and also as combination therapy with drugs like metformin and sitagliptin.

An Updated Review Summarizing the Anticancer Efficacy of Melittin from Bee Venom in Several Models of Human Cancers.

Apitherapy (using bee products) has gained broad recognition in cancer therapeutics globally. Honeybee venom has a broad range of biological potential, and its utilization is rapidly emerging in apitherapy. Bee products have significant potential to strengthen the immune system and improve human health. Thus, this review is targeted toward recapitulating the chemo-preventive potential of melittin (MEL), which constitutes a substantial portion of honeybee venom. Honeybee venom (apitoxin) is produced in the venom gland of the honeybee abdomen, and adult bees utilize it as a primary colony defense mechanism. Apitoxin comprises numerous biologically active compounds, including peptides, enzymes, amines, amino acids, phospholipids, minerals, carbohydrates, and volatile components. We are mainly focused on exploring the potential of melittin (a peptide component) of bee venom that has shown promising potential in the treatment of several human cancers, including breast, stomach, lung, prostate, ovary, kidney, colon, gastric, esophageal, cervical cancers, melanoma, osteosarcoma, and hepatocellular carcinoma. This review has summarized all potential studies related to the anticancerous efficacy of melittin (apitoxin), its formulations, conjugates, and nano-formulations against several human carcinomas, which would further pave the way for future researchers in developing potent drugs for cancer management.

Targeting Wnt/ß-Catenin Pathway by Flavonoids: Implication for Cancer Therapeutics.

The Wnt pathway has been recognized for its crucial role in human development and homeostasis, but its dysregulation has also been linked to several disorders, including cancer. Wnt signaling is crucial for the development and metastasis of several kinds of cancer. Moreover, members of the Wnt pathway have been proven to be effective biomarkers and promising cancer therapeutic targets. Abnormal stimulation of the Wnt signaling pathway has been linked to the initiation and advancement of cancer in both clinical research and in vitro investigations. A reduction in cancer incidence rate and an improvement in survival may result from targeting the Wnt/ß-catenin pathway. As a result, blocking this pathway has been the focus of cancer research, and several candidates that can be targeted are currently being developed. Flavonoids derived from plants exhibit growth inhibitory, apoptotic, anti-angiogenic, and anti-migratory effects against various malignancies. Moreover, flavonoids influence different signaling pathways, including Wnt, to exert their anticancer effects. In this review, we comprehensively evaluate the influence of flavonoids on cancer development and metastasis by focusing on the Wnt/ß-catenin signaling pathway, and we provide evidence of their impact on a number of molecular targets. Overall, this review will enhance our understanding of these natural products as Wnt pathway modulators.

Gut microbiome in cancer immunotherapy: Current trends, translational challenges and future possibilities.

Gut microbiota is regarded as a crucial regulator of the immune system. Healthy gut microbiota plays a specialized role in host xenobiotics, nutrition, drug metabolism, regulation of the structural integrity of the gut mucosal barrier, defense against infections, and immunomodulation. It is now understood that any imbalance in gut microbiota composition from that present in a healthy state is linked to genetic susceptibility to a number of metabolic disorders, including diabetes, autoimmunity, and cancer. Recent research has suggested that immunotherapy can treat many different cancer types with fewer side effects and better ability to eradicate tumors than conventional chemotherapy or radiotherapy. However, a significant number of patients eventually develop immunotherapy resistance. A strong correlation was observed between the composition of the gut microbiome and the effectiveness of treatment by examining the variations between populations that responded to immunotherapy and those that did not. Therefore, we suggest that modulating the microbiome could be a potential adjuvant therapy for cancer immunotherapy and that the architecture of the gut microbiota may be helpful in explaining the variation in treatment response. Herein, we focus on recent research on the interactions among the gut microbiome, host immunity, and cancer immunotherapy. In addition, we highlighted the clinical manifestations, future opportunities, and limitations of microbiome manipulation in cancer immunotherapy.