Review
Biochemistry & Molecular Biology
Shengliang Zhang, Lindsey Carlsen, Liz Hernandez Borrero, Attila A. Seyhan, Xiaobing Tian, Wafik S. El-Deiry
Summary: This article summarizes the current progress in targeting wild-type and mutant p53 for cancer therapy using biotherapeutic and biopharmaceutical methods. Strategies include boosting p53 activity, restoring p53 pathway function, targeting p53 in immunotherapy, and combination therapies.
Article
Biochemistry & Molecular Biology
Vidhi Malik, Navaneethan Radhakrishnan, Sunil C. Kaul, Renu Wadhwa, Durai Sundar
Summary: The study suggests that Withaferin-A and Withanone from Ashwagandha have potential as natural drugs for the treatment of Chronic Myeloid Leukemia. These compounds interact with the protein kinase ABL, and inhibition of ABL may contribute to their anticancer activity.
Review
Cell Biology
A-Rum Yoon, Renu Wadhwa, Sunil C. Kaul, Chae-Ok Yun
Summary: This review provides a comprehensive overview of the role of Mortalin in tumor biology and discusses the potential applications of anti-Mortalin molecules in cancer treatment.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Chemistry, Medicinal
Vipul Kumar, Jaspreet Kaur Dhanjal, Anissa Nofita Sari, Mallika Khurana, Sunil C. Kaul, Renu Wadhwa, Durai Sundar
Summary: This study demonstrated the differential binding ability of withaferin A, withanone, and caffeic acid phenethyl ester to DNMT1 and DNMT3A, leading to their inactivation and subsequent hypomethylation and desilencing of the tumor suppressor p16INK4A in cancer cells. Among the test compounds, withaferin A showed the strongest anticancer effect.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Navaneethan Radhakrishnan, Jaspreet Kaur Dhanjal, Anissa Nofita Sari, Yoshiyuki Ishida, Keiji Terao, Sunil C. Kaul, Durai Sundar, Renu Wadhwa
Summary: The study investigated the potential interaction of caffeic acid phenethyl ester (CAPE) with p53(Y220C) and found that it could restore the wild type p53 (p53(wt)) function, suggesting CAPE as a potential natural drug for treating cancers with p53(Y220C) mutations.
Article
Biochemistry & Molecular Biology
Deepankar Sharma, Ravi Saini, Abha Mishra
Summary: Tuberculosis is a major infectious disease with high mortality rates worldwide, mainly due to the emergence of antibiotic resistant strains. The pathogen uses L-asparaginase enzyme as a virulence factor, making it a potential therapeutic target. This study identified three phytocompounds from medicinal plants that showed strong binding potential to the enzyme. Molecular docking and dynamics simulations confirmed their stability at the catalytic site. These phytocompounds have the potential to be used as safe and low-cost alternatives to chemical compounds for tuberculosis treatment.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Oncology
Jiahao Hu, Jiasheng Cao, Win Topatana, Sarun Juengpanich, Shijie Li, Bin Zhang, Jiliang Shen, Liuxin Cai, Xiujun Cai, Mingyu Chen
Summary: TP53 is a critical tumor-suppressor gene commonly mutated in human cancers, with potential oncogenic properties when mutated. Treatments for cancers with mutant p53 involve targeting mutant p53 directly, restoring wild-type functions, and exploring synthetic lethal interactions with mutant p53 for therapeutic benefits. Additionally, disrupting noncoding RNA networks may have potential synthetic lethal effects in cancers with p53 mutations.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Oncology
Jie Jiang, Li Gao, Yongting Lan, Yang Wang, Peiqing Zhao
Summary: Previous studies have shown that TIPE1 acts as a tumor suppressor gene in several tumor types, but in cervical cancer, it promotes proliferation by inhibiting p53 activity, suppressing cell apoptosis, and facilitating chemoresistance in a p53-dependent manner. This suggests that TIPE1 plays a crucial role in the transition from chemosensitivity to chemoresistance and could be a potential target for cervical cancer chemotherapy.
FRONTIERS IN ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Renu Wadhwa, Neetu Singh Yadav, Shashank P. Katiyar, Tomoko Yaguchi, Chohee Lee, Hyomin Ahn, Chae-Ok Yun, Sunil C. Kaul, Durai Sundar
Summary: The study used molecular dynamics simulations to predict the membrane permeability of two natural drugs and confirmed the higher permeation of withaferin-A compared to withanone. The interaction between withaferin-A and the membrane was found to be the major driving force for its high permeability.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Shibo Huang, Bo Cao, Jieqiong Wang, Yiwei Zhang, Elisa Ledet, Oliver Sartor, Yuqin Xiong, Shelya X. Zeng, Hua Lu
Summary: The study identifies a novel form of p53 mutation, p53 long C-terminus (p53LC), present in various human cancers, which exhibits loss-of-function and dominant-negative effects. These mutants interact with wild-type p53, retaining it in the cytoplasm and preventing it from binding to target gene promoters, thereby inhibiting its transcriptional activity. Additionally, the mutants render p53-containing cancer cells insensitive to p53-activating agents.
JOURNAL OF MOLECULAR CELL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Mehregan Babamohamadi, Esmaeil Babaei, Burhan Ahmed Salih, Mahshid Babamohammadi, Hewa Jalal Azeez, Goran Othman
Summary: The p53 protein is a tumor suppressor that regulates various cellular processes and is closely related to cancer development. It can be used as a biomarker for tumor progression and a target for cancer treatment. This review discusses the contribution of wild-type p53 loss of function, its role in ferroptosis and targeted therapy, and challenges and solutions in p53-related drug delivery systems.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Cell Biology
Yingfang Shi, Shengxi Xu, Sen Li
Summary: The study found that the combination of HDACi tucidinostat and XPO1 inhibitor selinexor has better inhibitory activities on wt-TP53 BC cells, and can suppress proliferation and invasion and promote apoptosis by enhancing p53 activity in the nucleus.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2022)
Article
Cell Biology
Yueyuan Wang, Zhihao Zhang, Xuguang Mi, Mingxi Li, Dan Huang, Tingting Song, Xiaoyan Qi, Ming Yang
Summary: This study demonstrates that increasing functional p53 expression enhances the sensitivity of breast cancer cells to THZ1. Active p53 and an intact p53 pathway are required for the increased THZ1 sensitivity. The accumulation of p53 in the nucleus and mitochondria during cell death is involved in this process. Additionally, extensive transcriptional disruption is identified as the mechanism underlying nutlin-3 and THZ1-induced death of breast cancer cells. Furthermore, the combination of nutlin-3 and THZ1 treatment amplifies gasdermin E cleavage.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Medicine, Research & Experimental
Bin Song, Jiajian Wang, Yixin Ren, Yongnan Su, Xueye Geng, Fan Yang, Hao Wang, Jihong Zhang
Summary: p53 is a transcription factor that activates gene expression for genomic stability, but many cancers have mutations in p53 that render it inactive. Butein, a small molecule, has been identified as a potential drug that can reactivate mutant p53 and restore its tumor-suppressing function. Through various mechanisms, Butein restores the DNA-binding ability of mutant p53, activates p53 target genes, and stabilizes both wild-type and mutant p53 proteins. This study suggests that Butein could be a promising therapeutic agent for cancers with specific p53 mutations.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Oncology
Stefanie Schuller, Jan Sieker, Philip Riemenschneider, Bianca Koehler, Elisabeth Drucker, Sofia M. E. Weiler, Daniel Dauch, Carsten Sticht, Benjamin Goeppert, Stephanie Roessler, Silvia Ribback, Kai Breuhahn, Falko Fend, Frank Dombrowski, Kerstin Singer, Stephan Singer
Summary: The tumor suppressor protein P53 plays a crucial role in preventing liver cancer development, and it negatively regulates the expression of HELLS, an important regulator in liver cancer. The regulatory mechanism involves the induction of P21 and repression of FOXM1, resulting in the downregulation of HELLS expression. This study provides new insights into the epigenetic regulation of liver cancer and the tumor suppressive function of P53.
Article
Biochemistry & Molecular Biology
Vipul Kumar, Jaspreet Kaur Dhanjal, Priyanshu Bhargava, Ashish Kaul, Jia Wang, Huayue Zhang, Sunil C. Kaul, Renu Wadhwa, Durai Sundar
Summary: A study examined the binding potential of natural compounds Withaferin-A, Withanone, and caffeic acid phenethyl ester to the cell surface receptor TMPRSS2 using molecular docking and molecular dynamics simulations. The results showed that Withanone had stronger interactions with TMPRSS2 and was able to induce changes in its allosteric site. Furthermore, Withanone downregulated TMPRSS2 mRNA expression, suggesting its potential dual action in blocking SARS-CoV-2 entry into host cells.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Rajkumar Singh Kalra, Vipul Kumar, Jaspreet Kaur Dhanjal, Sukant Garg, Xiaoshuai Li, Sunil C. Kaul, Durai Sundar, Renu Wadhwa
Summary: Research shows that withanolides derived from Ashwagandha have potential therapeutic effects against the SARS-CoV-2 virus by inhibiting the ACE2 protein. Among them, stem extracts demonstrate higher inhibitory potency.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Oncology
Rajkumar S. Kalra, Gaurav S. Soman, Pradeep B. Parab, Avinash M. Mali, Sagar S. Varankar, Rutika R. Naik, Swapnil C. Kamble, Jaspreet K. Dhanjal, Sharmila A. Bapat
Summary: The monoclonal antibody mAb150 targets cancer stem cells, promoting their reentry into the cell cycle and disrupting tumor dormancy, leading to effective tumor targeting.
TRANSLATIONAL ONCOLOGY
(2022)
Article
Oncology
Anissa Nofita Sari, Jaspreet Kaur Dhanjal, Ahmed Elwakeel, Vipul Kumar, Hazna Noor Meidinna, Huayue Zhang, Yoshiyuki Ishida, Keiji Terao, Durai Sundar, Sunil C. Kaul, Renu Wadhwa
Summary: A combination of low doses of Wi-A and CAPE, two natural compounds found in Ashwagandha leaves and propolis, respectively, exhibits potent anti-migratory and anti-angiogenic activities. This combination acts on cell adhesion/tight junction proteins and inhibits Wnt/β-catenin signaling pathways, leading to the downregulation of EMT-signaling proteins. These findings suggest that this combination may be a potential therapeutic option for metastatic and aggressive cancers.
Review
Biochemistry & Molecular Biology
Jaspreet Kaur Dhanjal, Rajkumar Singh Kalra
Summary: Cancer is a disease caused by perturbed genes, with driver mutations dictating the functional impacts and progression of the disease. Recently, there has been significant attention on identifying driver events from genomic alterations to develop precision cancer therapies. Predicting cancer drivers using genetic signatures and protein structures can provide more clinically relevant evidence than genetic variations alone.
CURRENT PROTEIN & PEPTIDE SCIENCE
(2022)
Article
Oncology
Spyros Foutadakis, Eugenia Roupakia, Panagiotis Liakopoulos, Petros Kolovos, Evangelos Kolettas
Summary: Transcription Factors (TFs) are key regulators of gene expression, controlling aspects such as cell homeostasis, identity, and fate. NF-kappa B and E2F1 are important TFs involved in inflammation and cell cycle progression, respectively. This study compared their genomic binding profiles and found distinct preferences in the type of DNA elements they bind to. Additionally, NF-kappa B and E2F1 showed limited overlap in their binding sites and tended to bind to active chromatin even before stimulation. Furthermore, NF-kappa B was found to recruit E2F1 near pro-inflammatory genes following immune stimulation.
Article
Cell Biology
Hazna Noor Meidinna, Seyad Shefrin, Anissa Nofita Sari, Huayue Zhang, Jaspreet Kaur Dhanjal, Sunil C. Kaul, Durai Sundar, Renu Wadhwa
Summary: In this study, a novel compound called Mortaparib(Mild) was characterized for its ability to interact with mortalin, p53, and PARP1. The compound was found to downregulate the expression and functions of mortalin and PARP1, impeding cancer cell proliferation and migration. Mortaparib(Mild) shows potential as a candidate anticancer compound.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Virology
Neha Quadir, Jasdeep Singh, Anwar Alam, Asrar Ahmad Malik, Syed Asad Rahman, Subhash Hira, Nasreen Zafar Ehtesham, Durai Sundar, Seyed Ehtesham Hasnain
Summary: The acquisition of multiple mutations, including immune-escape mutations, by Omicron allows it to maintain a selection advantage within the population. Despite lower hospitalization and death rates, the surges in Omicron variants can still offset public health measures and disrupt healthcare facilities. The BA.4/BA.5 variants are found to be more severe than the earlier-emerged Omicron variants. Active COVID-19 surveillance can help understand the evolution and transmission patterns of new variants. The sudden decline in reported cases in low- and middle-income countries needs to be addressed to prevent undetected spread.
Editorial Material
Genetics & Heredity
Jaspreet Kaur Dhanjal, Rajkumar Singh Kalra, Dhanendra Tomar, Amrendra K. Ajay
FRONTIERS IN GENETICS
(2023)
Article
Geriatrics & Gerontology
Huayue Zhang, Jia Wang, Jay Prakash, Zhenya Zhang, Sunil C. Kaul, Renu Wadhwa
Summary: A variety of environmental stresses are associated with negative impacts on quality of life and health, including metabolic disorders, cognitive impairment, and accelerated aging. Despite advancements in drug development, there are limited options for stress management. Cell-based screening identified several compounds, including Withaferin-A (Wi-A), methoxy Withaferin-A (mWi-A), Withanone (Wi-N), triethylene glycol (TEG), and Ashwagandha (Withania somnifera) leaf M2-DMSO extract (M2DM), that showed potential in protecting cells from oxidative, metal, and hypoxia stresses.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Letter
Chemistry, Medicinal
Vipul Kumar, Anissa Nofita Sari, Hazna Noor Meidinna, Ashish Kaul, Brohmomoy Basu, Yoshiyuki Ishida, Keiji Terao, Sunil C. C. Kaul, Sudhanshu Vrati, Durai Sundar, Renu Wadhwa
PHYTOTHERAPY RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Dhvani Sandip Vora, Shashank Yadav, Durai Sundar
Summary: CRISPR/Cas9 technology allows precise genome editing and has contributed to various scientific and medical advancements. However, the unintentional off-target effects create a burden on the genome and hinder further research. Recent off-target prediction tools have used machine learning and deep learning techniques to better understand the potential off-targets, as the rules governing Cas9 activity are still not fully understood.
Article
Oncology
Rajkumar Singh Kalra, Anupama Chaudhary, Amr Omar, Xiaoshuai Li, Mallika Khurana, Sunil C. Kaul, Renu Wadhwa
Summary: Discovery of CARF as a protein that interacts with ARF and promotes ARF-p53p21WAF1 signaling and cellular senescence established its role in genomic stress. Further studies revealed its involvement in regulation of senescence, growth arrest, apoptosis, and malignant transformation in response to stress. This study assessed the quantitative impact of CARF expression level on these cell fates and found that CARF expression level can serve as a predictive measure of cell fates.
EXPERIMENTAL CELL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Maria Ntinopoulou, Dimitrios Cassimos, Eugenia Roupakia, Evangelos Kolettas, Maria Panopoulou, Elpis Mantadakis, Theocharis Konstantinidis, Akrivi Chrysanthopoulou
Summary: Elevated levels of neutrophil extracellular traps (NETs) and interleukin (IL)-17A were found in the sera of children during asthma exacerbation. The stimulation of control neutrophils with these sera resulted in IL-17A-enriched NET formation, which led to fibroblasts acquiring a pre-fibrotic phenotype and promoting fibrosis.