Browsing by Author "Avadhesh"

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Evaluation of Efficacy of Curcumin and Caffeic Acid Phenethyl Ester in Breast Cancer by Preclinical Studies
(Bentham Science Publishers, 2025) Sumit Singh Verma; Avadhesh; Ankit Srivastava; Anusmita Shekher; Anupam Dhasmana; Acharan Singh Narula; Subash Chandra Gupta
Aims: The aim of this study was to evaluate the combined and comparative efficacy of Caffeic acid phenethyl ester (CAPE) and curcumin in breast cancer. Background: CAPE and curcumin are a class of phenolics. While curcumin is obtained from turmeric, CAPE is found in Baccharis sarothroides and Populus deltoides. Both agents are reported to produce activities in some cancer types. The combined and comparative effects of the two agents in breast cancer have not yet reported. Objective: We evaluated the potential of CAPE and curcumin in both in vitro and in vivo breast cancer models. Methods: Human breast cancer cell lines, MDA-MB-231 and MCF-7, were exposed to CAPE and curcumin, followed by functional assays such as cell cytotoxicity, cell proliferation and colony formation, cell cycle, mitochondrial membrane potential, apoptosis, and monodansylcadaverine (MDC) staining for autophagy. Computational analyses and mouse models were also used. Results: Employing computational analyses, both agents were found to exhibit drug-like properties. Both molecules interacted with the key molecules of the NF-κB pathway. CAPE and curcumin inhibited cell proliferation, colony formation, and invasion, triggering apoptosis in breast cancer cells. CAPE was found to be more effective than curcumin. Two agents working together were more effective than each agent working alone. Both agents suppressed the expression of survivin, Bcl-xL and GLUT-1. The level of cleaved PARP was increased by both agents. Both phenolics observed an induction in ROS generation. Further, both molecules triggered a dissipation in mitochondrial membrane potential. In mice models implanted with Ehrlich-Lettre ascites carcinoma (EAC) cells, both drugs inhibited the growth of the tumour. The phenolics also modulated the metabolic parameters in tumour-bearing mice. Conclusion: The observations suggest that the combination of curcumin plus CAPE may be better in comparison to individual molecules. Other: The study opens a window for analysing the efficacy of the combination of CAPE and curcumin in animal studies. This will provide a basis for examining the combined efficacy of two agents in a clinical trial. © 2025 Bentham Science Publishers.
Immune checkpoint molecules in neuroblastoma: A clinical perspective
(Academic Press, 2022) Anup S. Pathania; Philip Prathipati; Swati P. Murakonda; Ajay B. Murakonda; Ankit Srivastava; Avadhesh; Siddappa N. Byrareddy; Don W. Coulter; Subash C. Gupta; Kishore B. Challagundla
High-risk neuroblastoma (NB) is challenging to treat with 5-year long-term survival in patients remaining below 50% and low chances of survival after tumor relapse or recurrence. Different strategies are being tested or under evaluation to destroy resistant tumors and improve survival outcomes in NB patients. Immunotherapy, which uses certain parts of a person's immune system to recognize or kill tumor cells, effectively improves patient outcomes in several types of cancer, including NB. One of the immunotherapy strategies is to block immune checkpoint signaling in tumors to increase tumor immunogenicity and anti-tumor immunity. Immune checkpoint proteins put brakes on immune cell functions to regulate immune activation, but this activity is exploited in tumors to evade immune surveillance and attack. Immune checkpoint proteins play an essential role in NB biology and immune escape mechanisms, which makes these tumors immunologically cold. Therapeutic strategies to block immune checkpoint signaling have shown promising outcomes in NB but only in a subset of patients. However, combining immune checkpoint blockade with other therapies, including conjugated antibody-based immunotherapy, radioimmunotherapy, tumor vaccines, or cellular therapies like modified T or natural killer (NK) cells, has shown encouraging results in enhancing anti-tumor immunity in the preclinical setting. An analysis of publicly available dataset using computational tools has unraveled the complexity of multiple cancer including NB. This review comprehensively summarizes the current information on immune checkpoint molecules, their biology, role in immune suppression and tumor development, and novel therapeutic approaches combining immune checkpoint inhibitors with other therapies to combat high-risk NB. © 2022
Moringin, an isothiocyanate modulates multiple cellular signalling molecules in breast cancer cells
(Elsevier Inc., 2024) Ankit Srivastava; Shruti Mishra; Avadhesh; Anusmita Shekher; Vipin Rai; Anupam Dhasmana; Jayanta Das; Daniele Perenzoni; Renato Iori; Subash C. Gupta
Prohibitin (PHB) is a pleiotropic molecule with a variety of known functions and subcellular locations. PHB's function in breast cancer is poorly understood. Herein, we report that PHB is expressed in cancer types of diverse origin including breast cancer. The cancer patients with changes in PHB were reported to have significantly reduced ‘overall survival’ in comparison to the cases without alterations in PHB. The expression of PHB was increased by H2O2 and also by Moringin (MG), which is an isothiocyanate derived from the seeds of Moringa oleifera. MG interacted with PHB, DRP1, and SLP2 and inhibited the growth of MCF-7 and MDAMB-231 cells. The isothiocyanate triggered apoptosis in breast cancer cells as revealed by AO/PI assay, phosphatidylserine externalization, cell cycle analysis and DAPI staining. MG induced proapoptotic proteins expression such as cytochrome c, p53, and cleaved caspase-7. Further, cell survival proteins such as survivin, Bcl-2, and Bcl-xL were suppressed. A depolarization of membrane potential suggested that the apoptosis was triggered through mitochondria. The isothiocyanate suppressed the cancer cell migration and interacted with NF-κB subunits. MG suppressed p65 nuclear translocation induced by TNF-α. The reactive oxygen species generation was also induced by the isothiocyanate in breast cancer cells. MG also modulated the expression of lncRNAs. Collectively, the functions of PHB in breast cancer growth is evident from this study. The activities of MG against breast cancer might result from its ability to modulate multiple cancer-related targets. © 2023
Role of IL-1 gene polymorphisms in common solid cancers
(Elsevier, 2023) Ragini D. Singh; Sagar Dholariya; Anusmita Shekher; Avadhesh; Deepak Parchwani; Subash C. Gupta
Because of the strong association of inflammation with cancer, the master cytokine, interleukin-1 (IL-1), has been extensively researched for its role in carcinogenesis. An appropriate, limited, targeted inflammatory response may provide protection to the host. However, on the other hand, an unusually protracted or severe inflammatory response may generate a microenvironment conducive to carcinogenesis. Inherited variants in the IL-1 gene affect its expression and eventually the molecular physiology of the IL-1 system. Studies have reported a wide variety of genetic variations inside the IL-1 gene cluster. Also, interpopulation differences in the distribution of polymorphic IL-1 genotypes are widespread. The polymorphic forms exert effects on cancer risk, development, and progression. This chapter focuses on the structure of the IL-1 gene, the polymorphisms reported in the IL-1 prototypes, i.e., IL1A, IL1B, and IL1RN, and the current knowledge on the involvement of polymorphic forms of IL-1 prototypes in cancer predisposition and prognosis, with particular emphasis on solid tumors. © 2023 Elsevier Inc. All rights reserved.