Browsing by Author "Varol, Mehmet"

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    Molecular mechanisms behind ROS regulation in cancer: A balancing act between augmented tumorigenesis and cell apoptosis
    (Springer Science and Business Media Deutschland GmbH, 2022-11-28T00:00:00) Tuli, Hardeep Singh; Kaur, Jagjit; Vashishth, Kanupriya; Sak, Katrin; Sharma, Ujjawal; Choudhary, Renuka; Behl, Tapan; Singh, Tejveer; Sharma, Sheetu; Saini, Adesh K.; Dhama, Kuldeep; Varol, Mehmet; Sethi, Gautam
    ROS include hydroxyl radicals (HO.), superoxide (O2.), and hydrogen peroxide (H2O2). ROS are typically produced under physiological conditions and play crucial roles in living organisms. It is known that ROS, which are created spontaneously by cells through aerobic metabolism in mitochondria, can have either a beneficial or detrimental influence on biological systems. Moderate levels of ROS can cause oxidative damage to proteins, DNA and lipids, which can aid in the pathogenesis of many disorders, including cancer. However, excessive concentrations of ROS can initiate programmed cell death in cancer. Presently, a variety of chemotherapeutic drugs and herbal agents are being investigated to induce ROS-mediated cell death in cancer. Therefore, preserving ROS homeostasis is essential for ensuring normal cell development and survival. On account of a significant association of ROS levels at various concentrations with carcinogenesis in a number of malignancies, further studies are needed to determine the underlying molecular mechanisms and develop the possibilities for intervening in these processes. � 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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    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, Anupam
    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 Ltd
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    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, Aklank
    Notch 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.
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    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 Kumar
    In 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 Ltd
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    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, Aklank
    As 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.