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Öğe 6-Phosphogluconate dehydrogenase fuels multiple aspects of cancer cells: From cancer initiation to metastasis and chemoresistance(Wiley, 2020) Sarfraz, Iqra; Rasul, Azhar; Hussain, Ghulam; Shah, Muhammad Ajmal; Zahoor, Ameer Fawad; Asrar, Muhammad; Selamoglu, ZelihaReprogrammed metabolism is key biochemical characteristic of malignant cells, which represents one of the emerging hallmarks of cancer. Currently, there is rising contemplation on oxidative pentose phosphate pathway (PPP) enzymes as potential therapeutic hits due to their affiliation with tumor metabolism. 6-Phosphogluconate dehydrogenase (6PGD), third oxidative decarboxylase of PPP, has received a great deal of attention during recent years due to its critical role in tumorigenesis and redox homeostasis. 6PGD has been reported to overexpress in number of cancer types and its hyperactivation is mediated through post-transcriptional and post-translational modifications by YTH domain family 2 (YTHDF2), Nrf2 (nuclear factor erythroid 2-related factor 2), EGFR (epidermal growth factor receptor) and via direct structural interactions with ME1 (malic enzyme 1). Upregulated expression of 6PGD provides metabolic as well as defensive advantage to cancer cells, thus, promoting their proliferative and metastatic potential. Moreover, enhanced 6PGD expression also performs key role in development of chemoresistance as well as radiation resistance in cancer. This review aims to discuss the historical timeline and cancer-specific role of 6PGD, pharmacological and genetic inhibitors of 6PGD and 6PGD as prognostic biomarker in order to explore its potential for therapeutic interventions. We anticipate that targeting this imperative supplier of NADPH might serve as tempting avenue to combat the deadly disease like cancer.Öğe A Review on Phyto-pharmacology of Oxalis corniculata(Bentham Science Publ Ltd, 2022) Sarfraz, Iqra; Rasul, Azhar; Hussain, Ghulam; Shah, Muhammad Ajmal; Nageen, Bushra; Jabeen, Farhat; Selamoglu, ZelihaOxalis corniculata (Oxalidaceae) is a small decumbent and delicate appearing medicinal herb flourishing in warm temperate and tropical domains such as Pakistan and India. Main bioactive chemical constituents of Oxalis plant include several alkaloids, flavonoids, terpenoids, cardiac glycosides, saponins, and phlobatannins, along with steroids. Due to its polyphenolic, glycosides and flavonoid profile, it is proved to be protective in numerous ailments and exhibit various biological activities such as anti-fungal, anti-cancer, anti-oxidant, anti-bacterial, anti-diabetic, and cardioprotective. Moreover, bioactive phytochemicals from this plant possess significant wound healing potential. Our current effort intends to emphasize on the immense significance of this plant species, which have not been the subject matter of clinical trials and effective pharmacological studies, even though its favored usage has been stated. This review proposes that Oxalis corniculata possess a potential for the cure of various diseases. However, further researches on isolation and characterization of bioactive compounds along with pre-clinical trials are compulsory to figure out its pharmacological applications.Öğe Alkaloids in the treatment of gastrointestinal tract cancer(Bentham Science Publishers, 2023) Riaz, Ammara; Rasul, Azhar; Batool, Rabia; Kanwal, Lubna; Hussain, Ghulam; Sarfraz, Iqra; Shah, Muhammad AjmalAlkaloids, nitrogen-containing compounds, are found in living organisms ranging from microbes to seed-producing plants all over the world. About more than 20,000 alkaloids have been discovered, mostly occurring in higher plants of the families Ranunculaceae, Papaveraceae, Leguminosae, Loganiaceae and Menispermaceae. These compounds are able to inhibit cancer proliferation, especially gastrointestinal cancer, which constitutes the highest incidence rate all over the world. The most diversified group of phytochemicals, alkaloids offer a mighty series of chemical scaffolds and moieties which can be harnessed to ameliorate the devastating consequences underlying cancer. Gastrointestinal (GIT) cancers constitute the malignancies of esophageal, gastric, pancreatic, colorectal and anal tumors, which possess aberrant metabolic signals giving rise to uncontrolled cell proliferation. These cancers are the most frequent of all cancers and account for the high mortality rates worldwide. Conventional therapeutic options carry the risks like being non-economical as well as they possess severe side effects. Natural products offer a wide spectrum of pharmacological properties which can overcome these risk factors by providing cheaper products and are reliable regarding their bio-safety profiles. Alkaloids can be investigated in detail to investigate their pharmacological potential against GIT cancers. Several alkaloids are known to modulate the cell signaling pathways by inducing cell cycle arrest at G0/G1, S and G2/M phases in addition to being the apoptosis inducers. In addition to that, they are also known to target various metabolic pathways, such as p53, B-catenin, MAPK and PIM3. The chapter intends to investigate the biological as well as pharmacological profiles of various alkaloids with special reference to GIT cancers in order to update scientists and researchers about the pharmaceutical potential of these compounds. © 2023 Bentham Science Publishers. All rights reserved.Öğe Biochanin A and biochanin B(Elsevier, 2021) Sarfraz, Iqra; Rasul, Azhar; Riaz, Ammara; Ucak, Ilknur; Zahoor, Muhammad Kashif; Hussain, Ghulam; Nawaz, JavariaNatural products have emerged as a treasure trove of novel chemical scaffolds for drug discovery against various diseases including inflammation, cardiovascular diseases, osteoporosis, and cancer. Isoflavones, polyphenolic compounds, from plants belonging to the Fabaceae family act as phytoestrogens and possess a pseudo-hormonal effect by binding with estrogen receptors in the human body. Due to this property, isoflavones exhibit multiple health-promoting benefits. In the class of isoflavones, biochanin A and biochanin B (formononetin) are prominent compounds renowned for their wide therapeutic window against numerous pathological conditions. Biochanin A and B possess antidiabetic, antiobesity, hepatoprotective, anticancer, and antiinflammatory activities. Biochanin A and B are rapidly absorbed in the body and possess safe pharmacokinetics as indicated by several in vivo investigations. This chapter aims to elaborate on the natural sources, pharmacological potential as well as bioavailability and pharmacokinetics of biochanin A and B, suggesting these compounds as interesting and safe candidates for drug design and development in the near future. © 2021 Elsevier Inc.Öğe Cardamonin: A new player to fight cancer via multiple cancer signaling pathways(Pergamon-Elsevier Science Ltd, 2020) Nawaz, Javaria; Rasul, Azhar; Shah, Muhammad Ajmal; Hussain, Ghulam; Riaz, Ammara; Sarfraz, Iqra; Zafar, SabaNature's pharmacy has undoubtedly served humans as an affordable and safer health-care regime for a long times. Cardamonin, a chalconoid present in several plants has been known for a longtime to have beneficial properties towards human health. In this review, we aimed to highlight the recent advances achieved in discovering the pharmacological properties of cardamonin. Cardamonin is cardamom-derived chalcone, which plays a role in cancer treatment, immune system modulation, inflammation and pathogens killing. Through the modulation of cellular signaling pathways, cardamonin activates cell death signal to induce apoptosis in malignant cells that results in the inhibition of cancer development. Moreover, cardamonin arrests cell cycle by altering the expression of regulatory proteins during malignant cells division. Due to its relatively selective cytotoxic potential against host malignant cells, cardamonin is emerging as a promising novel experimental anticancer agent. The potential of cardamonin to target various signaling molecules, transcriptional factors, cytokines and enzymes, such as mTOR, NF-kappa B, Akt, STAT3, Wnt/beta-catenin and COX-2 enhances the opportunity to explore it as a new multi-target therapeutic agent. The pharmacokinetic and biosafety profile of cardamonin favor it as a potentially safe biomolecule for pharmaceutical drug development.Öğe Curcumol: From Plant Roots to Cancer Roots(Ivyspring Int Publ, 2019) Wei, Wei; Rasul, Azhar; Sadiqa, Ayesha; Sarfraz, Iqra; Hussain, Ghulam; Nageen, Bushra; Liu, XintongNatural products, an infinite treasure of bioactive scaffolds, have provided an excellent reservoir for the discovery of drugs since millennium. These naturally occurring, biologically active and therapeutically effective chemical entities have emerged as novel paradigm for the prevention of various diseases. This review aims to give an update on the sources as well as pharmacological profile of curcumol, a pharmacologically active sesquiterpenoid, which is an imperative bioactive constituent of several plants mainly from genus Curcuma. Curcumol has potential to fight against cancer, oxidative stress, neurodegeneration, microbial infections, and inflammation. Curcumol has been documented as potent inducer of apoptosis in numerous cancer cells via targeting key signaling pathways as MAPK/ERK, PI3K/Akt and NF-kappa B which are generally deregulated in several cancers. The reported data reveals multitarget activity of curcumol in cancer treatment suggesting its importance as anticancer drug in future. It is speculated that curcumol may provide an excellent opportunity for the cure of cancer but further investigations on mechanism of its action and preclinical trials are still mandatory to further validate the potential of this natural cancer killer in anticancer therapies.Öğe Dietary polyphenols as therapeutic agents to combat COVID-19(Elsevier, 2022) Sarfraz, Iqra; Rasul, Azhar; Adem, Şevki; Ucak, Ilknur; Sarfraz, Ayesha; Bukhari, Shazia Anwer; Elfiky, Abdo A.The emerging outbreak of COVID-19 infection posed serious threat to human lives, claiming thousands of deaths worldwide. Both the emergence and subsequent transmission of SARS-CoV-2 underscore the urgent and critical need for the identification and development of effective preventive and therapeutic agents against COVID-19. This chapter aims to focus on promising anti-COVID-19 dietary polyphenols such as hesperidin, naringenin, Epigallocatechin gallate, and curcumin, their mechanism of action, safe dosage, toxicity, and bioavailability for future public health practices and research. Based on various computational, in vitro and in vivo pieces of evidence supporting efficacy, safety, and good bioavailability of polyphenols, this chapter demonstrates the potential of these entities for the prevention and development of therapeutics for the management of COVID-19. Although dietary polyphenols have been systematically studied from pharmacological point of view, a vast field of pr-clinical and clinical exploration still appears to be open for the research to fully validate their potential for the treatment of viral infections. © 2022 Elsevier Inc. All rights reserved.Öğe Enzyme assay techniques and protocols(Elsevier, 2022) Sarfraz, Iqra; Rasul, Azhar; Ucak, Ilknur; Lai, Ngit Shin; Asrar, Muhammad; Adem, ŞevkiEnzyme assays are standardized experimental protocols, which are established in order to measure the activity or concentration of enzymes in biochemical or cell-based systems. Mostly enzymatic assays are based upon the detection of fluorescent, luminescent, or spectrophotometric endpoint signal. During recent years, florescence-based, absorbance-based, and luminescence-based high-throughput screening assays have been developed and widely used in various fields. Enzyme assays represent an important tool for screening of sample libraries in context of drug discovery. In addition, enzyme assays are valuable for diagnosis of several diseases in clinical settings due to their high sensitivity, specificity, and rapid response. In this chapter, we aim to provide an understanding of the working principle of enzymatic assays and their applications with some specific examples of enzyme assays that are used for drug discovery and diagnostic purpose. © 2022 Elsevier Inc. All rights reserved.Öğe Eupatilin: a natural pharmacologically active flavone compound with its wide range applications(Taylor & Francis Ltd, 2020) Nageen, Bushra; Sarfraz, Iqra; Rasul, Azhar; Hussain, Ghulam; Rukhsar, Fariha; Irshad, Somia; Riaz, AmmaraEupatilin (5,7-dihydroxy-3 ',4 ',6-trimethoxyflavone) is a pharmacologically active flavone which has been isolated from a variety of medicinal plants. Eupatilin is known to possess various pharmacological properties such as anti-cancer, anti-oxidant, and anti-inflammatory. It is speculated that eupatilin could be subjected to structural optimization for the synthesis of derivative analogs to reinforce its efficacy, to minimize toxicity, and to optimize absorption profiles, which will ultimately lead towards potent drug candidates. Although, reported data acclaim multiple pharmacological activities of eupatilin but further experimentations on its molecular mechanism of action are yet mandatory to elucidate full spectrum of its pharmacological activities.Öğe Ficus benghalensis: A plant with potential pharmacological properties, from tradition to pharmacy(Pharmacotherapy Group, 2023) Tahir, Muhammad Mateen; Rasul, Azhar; Riaz, Ammara; Batool, Rabia; Nageen, Bushra; Adnan, Muhammad; Sarfraz, IqraPurpose: To undertake an overview of the potential pharmacological properties of Ficus benghalensisis.Methods: Data were acquired from several online sources, including Scopus, Elsevier Science Direct, PubMed, and Sci-Hub, using the keywords Ficus benghalensis, medicinal plants, anti-oxidant, anti-inflammatory, and anti-cancer.Results: Ficus benghalensis has valuable secondary metabolites including terpenoids, ketones, coumarins, oentacyclic, furocoumarin, flavonols, flavonoids, sterols, esters, carbohydrates, carboxylic acid, and polycyclic aromatic hydrocarbons. Due to its phytochemical profile, it is regarded as a plant with potential pharmacological properties such as anti-diarrheal, anti-inflammatory, anti-cancer, anti-oxidant, anti-bacterial, anti-diabetic, anti-tumor, immunomodulatory, anthelmintic, and anti-angiogenic. This review highlights the phytochemistry, traditional uses and pharmacological potential of Ficus benghalensis.Conclusion: Ficus benghalensis has potentials for treating several ailments. However, further research, including in vivo studies and preclinical trials, is necessary to ascertain its biological and pharmacological uses accurately.Öğe Ginkgetin: A natural biflavone with versatile pharmacological activities(Pergamon-Elsevier Science Ltd, 2020) Adnan, Muhammad; Rasul, Azhar; Hussain, Ghulam; Shah, Muhammad Ajmal; Zahoor, Muhammad Kashif; Anwar, Haseeb; Sarfraz, IqraNatural products, being richly endowed with curative powers, have become spotlight for biomedical and pharmaceutical research to develop novel therapeutics during recent years. Ginkgetin (GK), a natural non-toxic biflavone, has been shown to exhibit anti-cancer, anti-inflammatory, anti-microbial, anti-adipogenic, and neuroprotective activities. GK combats cancer progression by arresting cell cycle, inducing apoptosis, stimulating autophagy, and targeting many deregulated signaling pathways such as JAK/STAT and MAPKs. GKhalts inflammation mediators like interleukins, iNOS, COX-2, PGE2, NF-0, and acts as an inhibitor of PLA2. GK shows strong neuroprotection against oxidative stress-promoted cell death, inhibits cerebral micro -hemorrhage, decreases neurologic deficits, and halts apoptosis of neurons. GK also acts as anti-fungal, anti-viral, anti-bacterial, leishmanicidal and anti-plasmodial agent. GK shows substantial preventive or therapeutic effects in in vivo models of many diseases including atherosclerosis, cancer, neumdegenerative, hepatic, influenza, and inflammatory diseases. Based on various computational, in vitro and in vivo evidences, this article demonstrates the potential of ginkgetin for development of therapeutics against various diseases. Although GK has been systematically studied from pharmacological point of view, a vast field of pharmacokinetics, pre-clinical and clinical studies is still open for the researchers to fully validate its potential for the treatment of various diseases.Öğe Identification of Macrolepiota procera extract as a novel G6PD inhibitor for the treatment of lung cancer(Elsevier, 2022) Zara, Rabia; Rasul, Azhar; Sultana, Tayyaba; Jabeen, Farhat; Selamoglu, ZelihaTumor metabolism, an emerging hallmark of cancer, is characterized by aberrant expression of enzymes from various metabolic pathways including glycolysis and PPP (pentose phosphate pathway). Glucose 6 phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD), oxidative carboxylases of PPP, have been reported to accomplish different biosynthetic and energy requirements of cancer cells. G6PD and 6PGD have been proposed as potential therapeutic targets for cancer therapy during recent years due to their overexpression in various cancers. Here, we have employed enzymatic assay based screening using in-house G6PD and 6PGD assay protocols for the identification of mushroom extracts which could inhibit G6PD or 6PGD enzymatic activity for implications in cancer therapy. For the fulfillment of the objectives of present study, nine edible mushrooms were subjected to green extraction for preparation of ethanolic extracts. 6xhis-G6PD and pET-28a-h6PGD plasmids were expressed in BL21-DE3 E. coli cells for the expression and purification of protein of interests. Using purified proteins, in house enzymatic assay protocols were established. The preliminary screening identified two extracts (Macrolepiota procera and Terfezia boudieri) as potent and selective G6PD inhibitors, while no extract was found highly active against 6PGD. Further, evaluation of anticancer potential of mushroom extracts against lung cancer cells revealed Macrolepiota procera as potential inhibitor of cancer cell proliferation with IC50 value of 6.18 lg/ml. Finally, screening of M. procera-derived compounds against G6PD via molecular docking has identified paraben, quercetin and syringic acid as virtual hit compounds possessing good binding affinity with G6PD. The result of present study provides novel findings for possible mechanism of action of M. procera extract against A549 via G6PD inhibition suggesting that M. procera might be of therapeutic interest for lung cancer treatment.(c) 2022 The Authors. Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Öğe Jaceosidin: A Natural Flavone with Versatile Pharmacological and Biological Activities(Bentham Science Publ Ltd, 2021) Nageen, Bushra; Rasul, Azhar; Hussain, Ghulam; Shah, Muhammad A.; Anwar, Haseeb; Hussain, Syed M.; Uddin, Md SahabNature always remains an inexhaustible source of treasures for mankind. It remains a mystery for every challenge until the completion of the challenge. While we talk about the complicated health issues, nature offers us a great variety of chemical scaffolds and their various moieties packed in the form of natural products e.g., plants, microorganisms (fungi, algae, protozoa), and terrestrial vertebrates and invertebrates. This review article is an update about jaceosidin, a bioactive flavone, from genus Artemisia. This potentially active compound exhibits a variety of pharmacological activities including anti-inflammatory, anti-oxidant, anti-bacterial, anti-allergic and anti-cancer activities. The bioactivities and the therapeutic action of jaceosidin, especially the modulation of different cell signaling pathways (ERK1/2, NF-kappa B, PI3K/Akt and ATM-Chk1/2) which become deregulated in various pathological disorders, have been focused here. The reported data suggest that the bioavailability of this anti-cancer compound should be enhanced by utilizing various chemical, biological and computational techniques. Moreover, it is recommended that researchers and scientists should work on exploring the mode of action of this particular flavone to precede it further as a potent anti-cancer compound.Öğe Neurada procumbens promotes functions regain in a mouse model of mechanically induced sciatic nerve injury(Univ Karachi, 2019) Rasul, Azhar; Al-Shawi, Ali A. A.; Malik, Shoaib Ahmad; Anwar, Haseeb; Rasool, Bilal; Razzaq, Aroona; Aziz, NimraPeripheral nerve injury is a complex condition which results in restricted physical activity. Despite the tremendous efforts to figure out effective remedies, the complete functional retrieval is still a goal to be achieved. So, the need of hour is the exploration of potential natural compounds to recover this functional loss. Here, we have investigated the role of a local plant Neurada procumbens in ameliorating the functional recovery after an induced nerve compression injury in a mouse model. A dose of N. procumbens (50mg/kg of body weight) was administered orally from the day of injury to onwards. The motor functional recovery was assessed by evaluating muscle grip strength and sciatic functional index; while the sensory functions were gauged by the hotplate test. The serological parameters were carried out to analyze the effect of N. procumbens on oxidative stress level. The recovery of sensory and motor functions was significantly improved and perceived earlier in the treatment group. Moreover, the elevated antioxidant level was statistically significant in the treatment group. These results indicate that the supplementation of N. procumbens accelerates functional recovery after sciatic nerve crush injury.Öğe Nutrition and nutraceuticals for brain cancer(Nova Science Publishers, Inc., 2021) Sadiqa, Ayesha; Rasul, Azhar; Hussain, Ghulam; Shah, Muhammad Ajmal; Sarfraz, Iqra; Riaz, Ammara; Sarfraz, AyeshaBrain cancers are highly lethal and fatal human cancers due to various hurdles imposed by the brain's physiology and anatomy on therapeutic implications. Higher relapse rates and poor prognosis in brain cancers complicate the situation, leading to high mortalities. Therefore, it is the need of the hour to develop efficient therapeutic strategies against brain cancers. The exploitation of nutraceuticals is an emerging approach for the cure of cancers due to their safety, efficacy, and cost-effectiveness. This chapter focuses on the significance and mechanism of anti-brain cancer nutraceuticals such as juglone, formononetin, eugenol, curcumin, and biochanin. The anti-brain cancer activity of nutraceuticals is governed by the modulation of various cell signaling molecules such as apoptosis-related factors (caspase-3, caspase-9, Bax, Bid, Reactive oxygen species), cell cycle regulators (Cyclin D1, p53), protein kinases (FAK, p-ERK, p38 MAPK), enzymes (MMP-2, MMP-9), transcriptional factors (c-myc, Wnt, ?-catenin), and cytokines (TGF-?). The reported data recommend multitarget activity of nutraceuticals which might play an essential role in developing nutraceuticals to novel pharmacological drugs shortly. © 2021 Nova Science Publishers, Inc. All rights reserved.Öğe Oleandrin: A bioactive phytochemical and potential cancer killer via multiple cellular signaling pathways(Pergamon-Elsevier Science Ltd, 2020) Kanwal, Nazia; Rasul, Azhar; Hussain, Ghulam; Anwar, Haseeb; Shah, Muhammad Ajmal; Sarfraz, Iqra; Riaz, AmmaraNerium oleander, a member of family Apocynaceae, is commonly known as Kaner in various countries of Asia and Mediterranean region. This plant has been renowned to possess significant therapeutic potential due to its various bioactive compounds which have been isolated from this plant e.g., cardiac glycosides, oleandrin, a-tocopherol, digitoxingenin, umsolic acid, quercetin, odorosides, and adigoside. Oleandrin, a saponin glycoside is one of the most potent and pharmacologically active phytochemicals of N. oleander. Its remarkable pharmacotherapeutic potential have been interpreted as anticancer, anti-inflammatory, anti-HIV, neuropmtective, antimicrobial and antioxidant. This particular bioactive entity is known to target the multiple deregulated signaling cascades of cancer such as NF-kappa B, MAPK, and PI3K/Akt. The main focus of the current study is to comprehend the action mechanisms of oleandrin against various pathological conditions. The current review is a comprehensive summary to facilitate the researchers to understand the pharmacological position of the oleandrin in the arena of drug discovery, representing this compound as a new drug candidate for further researches. Moreover, in vivo and in silico based studies are required to explore the mechanistic approaches regarding the pharmacokinetics and biosafety profiling of this compound to completely track its candidature status in natural drug discovery.Öğe Osthole: A Multifunctional Natural Compound with Potential Anticancer, Antioxidant and Anti-inflammatory Activities(Bentham Science Publ Ltd, 2021) Zafar, Saba; Sarfraz, Iqra; Rasul, Azhar; Shah, Muhammad Ajmal; Hussain, Ghulam; Zahoor, Muhammad Kashif; Shafiq, NusratNature has always proved to be a significant reservoir of bioactive scaffolds that have been used for the discovery of drugs since times. Medicinal plants continue to be a solid niche for biologi-cally active and therapeutically effective chemical entities, opening up new avenues for the successful treatment of several human diseases. The contribution of plant-derived compounds to drug discovery, either in their original or in the semi-synthetic derivative form, extends far back in time. This review aims to focus on the sources, biological, and pharmacological profile of a pharmacologically active plant-derived coumarin, osthole, which is an important component of numerous remedial plants such as Cnidium monnieri. Several studies have revealed that osthole possess pharmacological properties such as anticancer, antioxidant, anti-hyperglycemic, neuroprotective, and antiplatelet. Osthole has been reported to regulate various signaling pathways, which in turn modulate several apoptosis-related pro-teins, cell cycle regulators, protein kinases, transcriptional factors, cytokines, and growth receptors affiliated with inflammation, proliferation and several other ailments. Osthole is known to halt prolif-eration and metastasis of cancerous cells by arresting the cell cycle and inducing apoptosis. The data in this review paper supports the pharmacological potential of osthole but further experimentation, biosafety profiling and synergistic effects of this compound need to be focused by the researchers to understand the full spectrum of pharmacological potential of this therapeutically potent compound.Öğe Phosphoglycerate mutase 1 in cancer: A promising target for diagnosis and therapy(Wiley, 2019) Sharif, Farzana; Rasul, Azhar; Ashraf, Asma; Hussain, Ghulam; Younis, Tahira; Sarfraz, Iqra; Chaudhry, Muhammad AsrarAltered enzymatic machineries are a substantial biochemical characteristic of tumor cell metabolism that switch metabolic profile from oxidative phosphorylation to amplified glycolysis as well as increased lactate production under hypoxia conditions. Reprogrammed metabolic profile is an emerging hallmark of cancer. Overexpression of several glycolytic enzymes and glucose transporters has been reported in 24 different types of cancers that represent approximately 70% of all the cancer cases around the globe. Thus, targeting glycolytic enzymes could serve as tempting avenue for drug design against cancer. Phosphoglycerate mutase 1 (PGAM1) is an important glycolytic enzyme that catalyzes the conversion of 3-phosphoglycerate to 2-phosphoglycerate. Recent investigations have revealed the overexpression of PGAM1 in several human cancers that is linked with tumor growth, survival, and invasion. The aim of this review is to update scientific research network with cancer-specific role of PGAM1 to elucidate its capability as bonafide therapeutic target for cancer therapy. Moreover, we have also summarized the reported genetic and pharmacological inhibitors of PGAM1. This study suggests that further investigations on PGAM1 should focus on the exploration of molecular mechanisms of PGAM1 overexpression in development of cancer, assessment of biosafety profiles of known inhibitors of PGAM1, and utilization of PGAM1 inhibitors in combinatorial therapies. These future studies will surely support the unbiased strategies for the development of novel PGAM1 inhibitors for cancer therapies.Öğe Physcion and Physcion 8-O-?-D-glucopyranoside: Natural Anthraquinones with Potential Anticancer Activities(Bentham Science Publ Ltd, 2021) Adnan, Muhammad; Rasul, Azhar; Hussain, Ghulam; Shah, Muhammad Ajmal; Sarfraz, Iqra; Nageen, Bushra; Riaz, AmmaraNature has provided prodigious reservoirs of pharmacologically active compounds for drug development since times. Physcion and physcion 8-O-beta-D-glucopyranoside (PG) are bioactive natural anthraquinones which exert anti-inflammatory and anticancer properties with minimum or no adverse effects. Moreover, physcion also exhibits anti-microbial and hepatoprotective properties, while PG is known to have anti-sepsis as well as ameliorative activities against dementia. This review aims to highlight the natural sources and anticancer activities of physcion and PG, along with associated mechanisms of actions. On the basis of the literature, physcion and PG regulate multitudinous cell signaling pathways through the modulation of various regulators of cell cycle, protein kinases, microRNAs, transcriptional factors, and apoptosis linked proteins resulting in the effective killing of cancerous cells in vitro as well as in vivo. Both compounds effectively suppress metastasis, furthermore, physcion acts as an inhibitor of 6PGD and also plays an important role in chemosensitization. This review article suggests that physcion and PG are potent anticancer drug candidates, but further investigations on their mechanism of action and pre-clinical trials are mandatory in order to comprehend the full potential of these natural cancer killers in anticancer remedies.Öğe Potential Anticancer Properties and Mechanisms of Action of Formononetin(Hindawi Ltd, 2019) Jiang, Dongjun; Rasul, Azhar; Batool, Rabia; Sarfraz, Iqra; Hussain, Ghulam; Tahir, Muhammad Mateen; Qin, TianNature, a vast reservoir of pharmacologically active molecules, has been most promising source of drug leads for the cure of various pathological conditions. Formononetin is one of the bioactive isoflavones isolated from different plants mainly from Trifolium pratense, Glycine max, Sophora flavescens, Pycnanthus angolensis, and Astragalus membranaceus. Formononetin has been well-documented for its anti-inflammatory, anticancer, and antioxidant properties. Recently anticancer activity of formononetin is widely studied. This review aims to highlight the pharmacological potential of formononetin, thus providing an insight of its status in cancer therapeutics. Formononetin fights progression of cancer via inducing apoptosis, arresting cell cycle, and halting metastasis via targeting various pathways which are generally modulated in several cancers. Although reported data acclaims various biological properties of formononetin, further experimentation on mechanism of its action, medicinal chemistry studies, and preclinical investigations are surely needed to figure out full array of its pharmacological and biological potential
