Browsing by Author "Iqubal, Ashif"
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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 Path of Silibinin from diet to medicine: A dietary polyphenolic flavonoid having potential anti-cancer therapeutic significance(Academic Press, 2020-10-29T00:00:00) Tuli, Hardeep Singh; Mittal, Sonam; Aggarwal, Diwakar; Parashar, Gaurav; Parashar, Nidarshana Chaturvedi; Upadhyay, Sushil Kumar; Barwal, Tushar Singh; Jain, Aklank; Kaur, Ginpreet; Savla, Raj; Sak, Katrin; Kumar, Manoj; Varol, Mehmet; Iqubal, Ashif; Sharma, Anil KumarIn the last few decades, targeting cancer by the use of dietary phytochemicals has gained enormous attention. The plausible reason and believe or mind set behind this fact is attributed to either lesser or no side effects of natural compounds as compared to the modern chemotherapeutics, or due to their conventional use as dietary components by mankind for thousands of years. Silibinin is a naturally derived polyphenol (a flavonolignans), possess following biochemical features; molecular formula C25H22O10, Molar mass: 482.44 g/mol, Boiling point 793 �C, with strikingly high antioxidant and anti-tumorigenic properties. The anti-cancer properties of Silibinin are determined by a variety of cellular pathways which include induction of apoptosis, cell cycle arrest, inhibition of angiogenesis and metastasis. In addition, Silibinin controls modulation of the expression of aberrant miRNAs, inflammatory response, and synergism with existing anti-cancer drugs. Therefore, modulation of a vast array of cellular responses and homeostatic aspects makes Silibinin an attractive chemotherapeutic agent. However, like other polyphenols, the major hurdle to declare Silibinin a translational chemotherapeutic agent, is its lesser bioavailability. After summarizing the chemistry and metabolic aspects of Silibinin, this extensive review focuses on functional aspects governed by Silibinin in chemoprevention with an ultimate goal of summarizing the evidence supporting the chemopreventive potential of Silibinin and clinical trials that are currently ongoing, at a single platform. � 2020 Elsevier LtdItem STAT signaling as a target for intervention: from cancer inflammation and angiogenesis to non-coding RNAs modulation(Springer Science and Business Media B.V., 2022-04-26T00:00:00) Tuli, Hardeep Singh; Sak, Katrin; Iqubal, Ashif; Garg, Vivek Kumar; Varol, Mehmet; Sharma, Uttam; Chauhan, Abhishek; Yerer, Mukerrem Betul; Dhama, Kuldeep; Jain, Manju; Jain, AklankAs a landmark, scientific investigation in cytokine signaling and interferon-related anti-viral activity, signal transducer and activator of transcription (STAT) family of proteins was first discovered in the 1990s. Today, we know that the STAT family consists of several transcription factors which regulate various molecular and cellular processes, including proliferation, angiogenesis, and differentiation in human carcinoma. STAT family members play an active role in transducing signals from cell membrane to nucleus through intracellular signaling and thus activating gene transcription. Additionally, they are also associated with the development and progression of human cancer by facilitating inflammation, cell survival, and resistance to therapeutic responses. Accumulating evidence suggests that not all STAT proteins are associated with the progression of human malignancy; however, STAT3/5 are constitutively activated in various cancers, including multiple myeloma, lymphoma, breast cancer, prostate hepatocellular carcinoma, and non-small cell lung cancer. The present review highlights how STAT-associated events are implicated in cancer inflammation, angiogenesis and non-coding RNA (ncRNA) modulation to highlight potential intervention into carcinogenesis-related cellular processes. � 2022, The Author(s), under exclusive licence to Springer Nature B.V.