Asifa Khan

Bio: Asifa Khan is an academic researcher from Jamia Millia Islamia. The author has contributed to research in topics: Cancer & Silibinin. The author has an hindex of 2, co-authored 4 publications receiving 16 citations.

Silibinin induces metabolic crisis in triple-negative breast cancer cells by modulating EGFR-MYC-TXNIP axis: potential therapeutic implications.

Abstract: Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with limited treatment modalities and poor prognosis. Metabolic reprogramming in cancer is considered a hallmark of therapeutic relevance. Here, we report disruption of metabolic reprogramming in TNBC cells by silibinin via modulation of EGFR-MYC-TXNIP signaling. Metabolic assays combined with LC-MS-based metabolomics revealed inhibition of glycolysis and other key biosynthetic pathways by silibinin, to induce metabolic catastrophe in TNBC cells. Silibinin-induced metabolic suppression resulted in decreased cell biomass, proliferation, and stem cell properties. Mechanistically, we identify EGFR-MYC-TXNIP as an important regulator of TNBC metabolism and mediator of inhibitory effects of silibinin. Highlighting the clinical relevance of our observations, the analysis of METABRIC dataset revealed deregulation of EGFR-MYC-TXNIP axis in TNBC and association of EGFRhigh -MYChigh -TXNIPlow signature with aggressive glycolytic metabolism and poor disease-specific and metastasis-free survival. Importantly, combination treatment of silibinin or 2-deoxyglucose (glycolysis inhibitor) with paclitaxel synergistically inhibited proliferation of TNBC cells. Together, our results highlight the importance of EGFR-MYC-TXNIP axis in regulating TNBC metabolism, demonstrate the anti-TNBC activity of silibinin, and argue in favor of targeting metabolic vulnerabilities of TNBC, at least in combination with mainstay chemotherapeutic drugs, to effectively treat TNBC patients.

Identification of plant-based hexokinase 2 inhibitors: combined molecular docking and dynamics simulation studies

Abstract: Cancer cells ferment glucose, even under aerobic conditions, following a phenomenon known as the ‘Warburg effect.’ Hexokinase 2 (HK2) catalyzes the crucial step of phosphorylation of glucose for su...

Phytocompounds Targeting Metabolic Reprogramming in Cancer: An Assessment of Role, Mechanisms, Pathways, and Therapeutic Relevance.

Abstract: The metabolism of cancer is remarkably different from that of normal cells and confers a variety of benefits, including the promotion of other cancer hallmarks. As the rewired metabolism is a near-universal property of cancer cells, efforts are underway to exploit metabolic vulnerabilities for therapeutic benefits. In the continued search for safer and effective ways of cancer treatment, structurally diverse plant-based compounds have gained substantial attention. Here, we present an extensive assessment of the role of phytocompounds in modulating cancer metabolism and attempt to make a case for the use of plant-based compounds in targeting metabolic vulnerabilities of cancer. We discuss the pharmacological interactions of phytocompounds with major metabolic pathways and evaluate the role of phytocompounds in the regulation of growth signaling and transcriptional programs involved in the metabolic transformation of cancer. Lastly, we examine the potential of these compounds in the clinical management of cancer along with limitations and challenges.

Recent Developments in Inonotus obliquus (Chaga mushroom) Polysaccharides: Isolation, Structural Characteristics, Biological Activities and Application

Abstract: Inonotus obliquus (Chaga mushroom) is a kind of medicine and health food widely used by folk in China, Russia, Korea, and some occidental countries. Among the extracts from Inonotus obliquus, Inonotus obliquus polysaccharide (IOPS) is supposed to be one of the major bioactive components in Inonotus obliquus, which possesses antitumor, antioxidant, anti-virus, hypoglycemic, and hypolipidemic activities. In this review, the current advancements on extraction, purification, structural characteristics, and biological activities of IOPS were summarized. This review can provide significant insight into the IOPS bioactivities as their in vitro and in vivo data were summarized, and some possible mechanisms were listed. Furthermore, applications of IOPS were reviewed and discussed; IOPS might be a potential candidate for the treatment of cancers and type 2 diabetes. Besides, new perspectives for the future work of IOPS were also proposed.

Andrographolide: A review of its pharmacology, pharmacokinetics, toxicity and clinical trials and pharmaceutical researches.

Abstract: Andrographis paniculata (Burm. f.) Wall. ex Nees, a renowned herb medicine in China, is broadly utilized in traditional Chinese medicine (TCM) for the treatment of cold and fever, sore throat, sore tongue, snake bite with its excellent functions of clearing heat and toxin, cooling blood and detumescence from times immemorial. Modern pharmacological research corroborates that andrographolide, the major ingredient in this traditional herb, is the fundamental material basis for its efficacy. As the main component of Andrographis paniculata (Burm. f.) Wall. ex Nees, andrographolide reveals numerous therapeutic actions, such as antiinflammatory, antioxidant, anticancer, antimicrobial, antihyperglycemic and so on. However, there are scarcely systematic summaries on the specific mechanism of disease treatment and pharmacokinetics. Moreover, it is also found that it possesses easily ignored security issues in clinical application, such as nephrotoxicity and reproductive toxicity. Thereby it should be kept a lookout over in clinical. Besides, the relationship between the efficacy and security issues of andrographolide should be investigated and evaluated scientifically. In this review, special emphasis is given to andrographolide, a multifunctional natural terpenoids, including its pharmacology, pharmacokinetics, toxicity and pharmaceutical researches. A brief overview of its clinical trials is also presented. This review intends to systematically and comprehensively summarize the current researches of andrographolide, which is of great significance for the development of andrographolide clinical products. Noteworthy, those un-cracked issues such as specific pharmacological mechanisms, security issues, as well as the bottleneck in clinical transformation, which detailed exploration and excavation are still not to be ignored before achieving integration into clinical practice. In addition, given that current extensive clinical data do not have sufficient rigor and documented details, more high-quality investigations in this field are needed to validate the efficacy and/or safety of many herbal products.

TXNIP: A Double-Edged Sword in Disease and Therapeutic Outlook

Abstract: Thioredoxin-interacting protein (TXNIP) was originally named vitamin D3 upregulated protein-1 (VDUP1) because of its ability to bind to thioredoxin (TRX) and inhibit TRX function and expression. TXNIP is an alpha-arrestin protein that is essential for redox homeostasis in the human body. TXNIP may act as a double-edged sword in the cell. The balance of TXNIP is crucial. A study has shown that TXNIP can travel between diverse intracellular locations and bind to different proteins to play different roles under oxidative stress. The primary function of TXNIP is to induce apoptosis or pyroptosis under oxidative stress. TXNIP also inhibits proliferation and migration in cancer cells, although TXNIP levels decrease, and function diminishes in various cancers. In this review, we summarized the main structure, binding proteins, pathways, and the role of TXNIP in diseases, aiming to explore the double-edged sword role of TXNIP, and expect it to be helpful for future treatment using TXNIP as a therapeutic target.

Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis

Abstract: The situation faced by breast cancer patients, especially those with triple-negative breast cancer, is still grave. More effective therapeutic targets are needed to optimize the clinical management of breast cancer. Although collagen type VIII alpha 1 chain (COL8A1) has been shown to be downregulated in BRIP1-knockdown breast cancer cells, its clinical role in breast cancer remains unknown. Gene microarrays and mRNA sequencing data were downloaded and integrated into larger matrices based on various platforms. Therefore, this is a multi-centered study, which contains 5048 breast cancer patients and 1161 controls. COL8A1 mRNA expression in breast cancer was compared between molecular subtypes. In-house immunohistochemistry staining was used to evaluate the protein expression of COL8A1 in breast cancer. A diagnostic test was performed to assess its clinical value. Furthermore, based on differentially expressed genes (DEGs) and co-expressed genes (CEGs) positively related to COL8A1, functional enrichment analyses were performed to explore the biological function and potential molecular mechanisms of COL8A1 underlying breast cancer. COL8A1 expression was higher in breast cancer patients than in control samples (standardized mean difference = 0.79; 95% confidence interval [CI] 0.55–1.03). Elevated expression was detected in various molecular subtypes of breast cancer. An area under a summary receiver operating characteristic curve of 0.80 (95% CI 0.76–0.83) with sensitivity of 0.77 (95% CI 0.69–0.83) and specificity of 0.70 (95% CI 0.61–0.78) showed moderate capacity of COL8A1 in distinguishing breast cancer patients from control samples. Worse overall survival was found in the higher than in the lower COL8A1 expression groups. Intersected DEGs and CEGs positively related to COL8A1 were significantly clustered in the proteoglycans in cancer and ECM-receptor interaction pathways. Elevated COL8A1 may promote the migration of breast cancer by mediating the ECM-receptor interaction and synergistically interplaying with DEGs and its positively related CEGs independently of molecular subtypes. Several genes clustered in the proteoglycans in cancer pathway are potential targets for developing effective agents for triple-negative breast cancer.