Department Of Zoology
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Item Recent advances in understanding brain cancer metabolomics: a review(Springer, 2023-07-10T00:00:00) Mukherjee, Anirban Goutam; Gopalakrishnan, Abilash Valsala; Jayaraj, Rama; Ganesan, Raja; Renu, Kaviyarasi; Vellingiri, Balachandar; Dey, Abhijit; Parveen, MohamudhaRegardless of the significant progress made in surgical techniques and adjuvant therapies, brain tumors are a major contributor to cancer-related morbidity and mortality in both pediatric and adult populations. Gliomas represent a significant proportion of cerebral neoplasms, exhibiting diverse levels of malignancy. The etiology and mechanisms of resistance of this malignancy are inadequately comprehended, and the optimization of patient diagnosis and prognosis is a challenge due to the diversity of the disease and the restricted availability of therapeutic options. Metabolomics refers to the comprehensive analysis of endogenous and exogenous small molecules, both in a targeted and untargeted manner, that enables the characterization of an individual�s phenotype and offers valuable insights into cellular activity, particularly in the context of cancer biology, including brain tumor biology. Metabolomics has garnered attention in current years due to its potential to facilitate comprehension of the dynamic spatiotemporal regulatory network of enzymes and metabolites that enables cancer cells to adapt to their environment and foster the development of tumors. Metabolic changes are widely acknowledged as a significant characteristic for tracking the advancement of diseases, treatment efficacy, and identifying novel molecular targets for successful medical management. Metabolomics has emerged as an exciting area for personalized medicine and drug discovery, utilizing advanced analytical techniques such as nuclear magnetic resonance spectroscopy (MRS) and mass spectrometry (MS) to achieve high-throughput analysis. This review examines and highlights the latest developments in MRS, MS, and other technologies in studying human brain tumor metabolomics. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Item Natural flavonoids exhibit potent anticancer activity by targeting microRNAs in cancer: A signature step hinting towards clinical perfection(Neoplasia Press, Inc., 2022-12-05T00:00:00) Tuli, Hardeep Singh; Garg, Vivek Kumar; Bhushan, Sakshi; Uttam, Vivek; Sharma, Uttam; Jain, Aklank; Sak, Katrin; Yadav, Vikas; Lorenzo, Jose M.; Dhama, Kuldeep; Behl, Tapan; Sethi, GautamCancer prevalence and its rate of incidence are constantly rising since the past few decades. Owing to the toxicity of present-day antineoplastic drugs, it is imperative to explore safer and more effective molecules to combat and/or prevent this dreaded disease. Flavonoids, a class of polyphenols, have exhibited multifaceted implications against several diseases including cancer, without showing significant toxicity towards the normal cells. Shredded pieces of evidence suggest that flavonoids can enhance drug sensitivity and suppress proliferation, metastasis, and angiogenesis of cancer cells by modulating several oncogenic or oncosuppressor microRNAs (miRNAs, miRs). They play pivotal roles in regulation of various biological and pathological processes, including various cancers. In the present review, the structure, chemistry and miR targeting efficacy of quercetin, luteolin, silibinin, genistein, epigallocatechin gallate, and cyanidin against several cancer types are comprehensively discussed. miRs are considered as next-generation medicine of recent times, and their targeting by naturally occurring flavonoids in cancer cells could be deemed as a signature step. We anticipate that our compilations related to miRNA-mediated regulation of cancer cells by flavonoids might catapult the clinical investigations and affirmation in the future. � 2022Item Herbal Remedies for Improving Cancer Treatment Through Modulation of Redox Balance(Springer Singapore, 2022-09-28T00:00:00) Kaur, Sukhchain; Verma, Harkomal; Kaur, Sharanjot; Singh, Subham; Mantha, Anil K.; Dhiman, MonishaThe redox modulation induced by oxidative stress is one of the major cause of the metabolic and inflammatory disorders including cancer. The reactive oxygen species (ROS) produced by various sources in the cell shift the redox homeostasis of cells towards more oxidizing or acidic environment. This shift results in the alterations of normal physiologic functioning of biomolecules as well as causes damage to these biomolecules (proteins, lipids, and DNA/RNA). The excessive ROS and redox modulation are the key factors that support growth, progression, and survival of cancer cells. ROS-induced redox modulation further activates pro-tumorigenic cellular pathways for e.g., PI3K/AKT, HIF-1, and MAPK signaling pathways as well as hinders epigenetic signaling. Increasing evidences demonstrate that long-term side effects of anti-cancer chemotherapy are major concern of medical sciences although modern treatments are quite effective. The combination of various herbal formulations with anti-cancer therapy shows improvement in treatment effectiveness in cancer patients. Bioactive compounds present in herbal formulations possess antioxidant and anti-cancer properties that help in the regulation of redox status of cancer cells. The synergetic effects of herbal remedies along with conventional treatment are proven as novel therapeutics in cancer progression management. Clinical studies have shown that broad range of herbs and bioactive compounds from various plants having antioxidant, anti-inflammatory properties can suppress the carcinogenesis. In this chapter we will discuss the role of various plants such as Glycyrrhiza glabra, Picrorhiza kurroa, Tinospora cordifolia, Curcuma longa, Ocimum sanctum, Viola odorata, and bioactive compound ferulic acid found in various cereals. The chapter will also focus on various mechanisms involved in the modulation of chemo-toxicity and improvement of efficacy of conventional anti-cancer therapies by these plants. � Springer Nature Singapore Pte Ltd. 2022.Item NOTCH signaling: Journey of an evolutionarily conserved pathway in driving tumor progression and its modulation as a therapeutic target(Elsevier Ireland Ltd, 2021-06-29T00:00:00) Aggarwal, Vaishali; Tuli, Hardeep Singh; Varol, Mehmet; Tuorkey, Muobarak; Sak, Katrin; Parashar, Nidarshana Chaturvedi; Barwal, Tushar Singh; Sharma, Uttam; Iqubal, Ashif; Parashar, Gaurav; Jain, AklankNotch signaling, an evolutionarily conserved signaling cascade, is critical for normal biological processes of cell differentiation, development, and homeostasis. Deregulation of the Notch signaling pathway has been associated with tumor progression. Thus, Notch presents as an interesting target for a variety of cancer subtypes and its signaling mechanisms have been actively explored from the therapeutic viewpoint. However, besides acting as an oncogene, Notch pathway can possess also tumor suppressive functions, being implicated in inhibition of cancer development. Given such interesting dual and dynamic role of Notch, in this review, we discuss how the evolutionarily conserved Notch signaling pathway drives hallmarks of tumor progression and how it could be targeted for a promising treatment and management of cancer. In addition, the up-to-date information on the inhibitors currently under clinical trials for Notch targets is presented along with how NOTCH inhibitors can be used in conjunction with established chemotherapy/radiotherapy regimes. � 2021 Elsevier B.V.Item Molecular mechanisms of action of epigallocatechin gallate in cancer: Recent trends and advancement(Academic Press, 2020-05-24T00:00:00) Aggarwal, Vaishali; Tuli, Hardeep Singh; Tania, Mousumi; Srivastava, Saumya; Ritzer, Erin E.; Pandey, Anjana; Aggarwal, Diwakar; Barwal, Tushar Singh; Jain, Aklank; Kaur, Ginpreet; Sak, Katrin; Varol, Mehmet; Bishayee, AnupamEpigallocatechin gallate (EGCG), also known as epigallocatechin-3-gallate, is an ester of epigallocatechin and gallic acid. EGCG, abundantly found in tea, is a polyphenolic flavonoid that has the potential to affect human health and disease. EGCG interacts with various recognized cellular targets and inhibits cancer cell proliferation by inducing apoptosis and cell cycle arrest. In addition, scientific evidence has illustrated the promising role of EGCG in inhibiting tumor cell metastasis and angiogenesis. It has also been found that EGCG may reverse drug resistance of cancer cells and could be a promising candidate for synergism studies. The prospective importance of EGCG in cancer treatment is owed to its natural origin, safety, and low cost which presents it as an attractive target for further development of novel cancer therapeutics. A major challenge with EGCG is its low bioavailability which is being targeted for improvement by encapsulating EGCG in nano-sized vehicles for further delivery. However, there are major limitations of the studies on EGCG, including study design, experimental bias, and inconsistent results and reproducibility among different study cohorts. Additionally, it is important to identify specific EGCG pharmacological targets in the tumor-specific signaling pathways for development of novel combined therapeutic treatments with EGCG. The present review highlights the ongoing development to identify cellular and molecular targets of EGCG in cancer. Furthermore, the role of nanotechnology-mediated EGCG combinations and delivery systems will also be discussed. � 2020 Elsevier LtdItem Molecular mechanisms of action of epigallocatechin gallate in cancer: Recent trends and advancement(Academic Press, 2020) Aggarwal, V; Tuli, H.S; Tania, M; Srivastava, S; Ritzer, E.E; Pandey, A; Aggarwal, D; Barwal, T.S; Jain, A; Kaur, G; Sak, K; Varol, M; Bishayee, A.Epigallocatechin gallate (EGCG), also known as epigallocatechin-3-gallate, is an ester of epigallocatechin and gallic acid. EGCG, abundantly found in tea, is a polyphenolic flavonoid that has the potential to affect human health and disease. EGCG interacts with various recognized cellular targets and inhibits cancer cell proliferation by inducing apoptosis and cell cycle arrest. In addition, scientific evidence has illustrated the promising role of EGCG in inhibiting tumor cell metastasis and angiogenesis. It has also been found that EGCG may reverse drug resistance of cancer cells and could be a promising candidate for synergism studies. The prospective importance of EGCG in cancer treatment is owed to its natural origin, safety, and low cost which presents it as an attractive target for further development of novel cancer therapeutics. A major challenge with EGCG is its low bioavailability which is being targeted for improvement by encapsulating EGCG in nano-sized vehicles for further delivery. However, there are major limitations of the studies on EGCG, including study design, experimental bias, and inconsistent results and reproducibility among different study cohorts. Additionally, it is important to identify specific EGCG pharmacological targets in the tumor-specific signaling pathways for development of novel combined therapeutic treatments with EGCG. The present review highlights the ongoing development to identify cellular and molecular targets of EGCG in cancer. Furthermore, the role of nanotechnology-mediated EGCG combinations and delivery systems will also be discussed. � 2020 Elsevier LtdItem Molecular mechanisms of action of genistein in cancer: Recent advances(Frontiers Media S.A., 2019) Tuli H.S.; Tuorkey M.J.; Thakral F.; Sak K.; Kumar M.; Sharma A.K.; Sharma U.; Jain A.; Aggarwal V.; Bishayee A.Background: Genistein is one among the several other known isoflavones that is found in different soybeans and soy products. The chemical name of genistein is 4?,5,7-trihydroxyisoflavone. Genistein has drawn attention of scientific community because of its potential beneficial effects on human grave diseases, such as cancer. Mechanistic insight of genistein reveals its potential for apoptotic induction, cell cycle arrest, as well as antiangiogenic, antimetastatic, and anti-inflammatory effects. Objective: The purpose of this review is to unravel and analyze various molecular mechanisms of genistein in diverse cancer models. Data sources: English language literature was searched using various databases, such as PubMed, ScienceDirect, EBOSCOhost, Scopus, Web of Science, and Cochrane Library. Key words used in various combinations included genistein, cancer, anticancer, molecular mechanisms prevention, treatment, in vivo, in vitro, and clinical studies. Study selection: Study selection was carried out strictly in accordance with the statement of Preferred Reporting Items for Systematic Reviews and Meta-analyses. Data extraction: Four authors independently carried out the extraction of articles. Data synthesis: One hundred one papers were found suitable for use in this review. Conclusion: This review covers various molecular interactions of genistein with various cellular targets in cancer models. It will help the scientific community understand genistein and cancer biology and will provoke them to design novel therapeutic strategies.Item Molecular mechanisms of action of tocotrienols in cancer: Recent trends and advancements(MDPI AG, 2019) Aggarwal, V; Kashyap, D; Sak, K; Tuli, H.S; Jain, Aklank; Chaudhary, A; Garg, V.K; Sethi, G; Yerer, M.B.Tocotrienols, found in several natural sources such as rice bran, annatto seeds, and palm oil have been reported to exert various beneficial health promoting properties especially against chronic diseases, including cancer. The incidence of cancer is rapidly increasing around the world not only because of continual aging and growth in global population, but also due to the adaptation of Western lifestyle behaviours, including intake of high fat diets and low physical activity. Tocotrienols can suppress the growth of different malignancies, including those of breast, lung, ovary, prostate, liver, brain, colon, myeloma, and pancreas. These findings, together with the reported safety profile of tocotrienols in healthy human volunteers, encourage further studies on the potential application of these compounds in cancer prevention and treatment. In the current article, detailed information about the potential molecular mechanisms of actions of tocotrienols in different cancer models has been presented and the possible effects of these vitamin E analogues on various important cancer hallmarks, i.e., cellular proliferation, apoptosis, angiogenesis, metastasis, and inflammation have been briefly analyzed. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.Item Understanding human thiol dioxygenase enzymes: structure to function and biology to pathology(Wiley, 2017) Sarkar, Bibekananda; Kulharia, Mahesh; Mantha, Anil K.Amino acid metabolism is a significant metabolic activity in humans, especially of sulphur-containing amino acids, methionine and cysteine (Cys). Cys is cytotoxic and neurotoxic in nature; hence, mammalian cells maintain a constant intracellular level of Cys. Metabolism of Cys is mainly regulated by two thiol dioxygenases: cysteine dioxygenase (CDO) and 2-aminoethanethiol dioxygenase (ADO). CDO and ADO are the only human thiol dioxygenases reported with a role in Cys metabolism and localized to mitochondria. This metabolic pathway is important in various human disorders, as it is responsible for the synthesis of antioxidant glutathione and is also for the synthesis of hypotaurine and taurine. CDO is the most extensively studied protein, whose high-resolution crystallographic structures have been solved. As compared to CDO, ADO is less studied, even though it has a key role in cysteamine metabolism. To further understand ADO’s structure and function, the three-dimensional structures have been predicted from I-TASSER and SWISS-MODEL servers and validated with PROCHECK software. Structural superimposition approach using iPBA web server further confirmed near-identical structures (including active sites) for the predicted protein models of ADO as compared to CDO. In addition, protein–protein interaction and their association in patho-physiology are crucial in understanding protein functions. Both ADO and CDO interacting partner profiles have been presented using STRING database. In this study, we have predicted a 3Dmodel structure for ADO and summarized the biological roles and the pathological consequences which are associated with the altered expression and functioning of ADO and CDO in case of cancer, neurodegenerative disorders and other human diseases.