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      Anticancer Potential of Furanocoumarins: Mechanistic and Therapeutic Aspects

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          Abstract

          Cancer is one of the most extreme medical conditions in both developing and developed countries around the world, causing millions of deaths each year. Chemotherapy and/or radiotherapy are key for treatment approaches, but both have numerous adverse health effects. Furthermore, the resistance of cancerous cells to anticancer medication leads to treatment failure. The rising burden of cancer overall requires novel efficacious treatment modalities. Natural medications offer feasible alternative options against malignancy in contrast to western medication. Furanocoumarins’ defensive and restorative impacts have been observed in leukemia, glioma, breast, lung, renal, liver, colon, cervical, ovarian, and prostate malignancies. Experimental findings have shown that furanocoumarins activate multiple signaling pathways, leading to apoptosis, autophagy, antioxidant, antimetastatic, and cell cycle arrest in malignant cells. Additionally, furanocoumarins have been shown to have chemo preventive and chemotherapeutic synergistic potential when used in combination with other anticancer drugs. Here, we address different pathways which are activated by furanocoumarins and their therapeutic efficacy in various tumors. Ideally, this review will trigger interest in furanocoumarins and their potential efficacy and safety as a cancer lessening agents.

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          Multiple functions of p21 in cell cycle, apoptosis and transcriptional regulation after DNA damage.

          An appropriate control over cell cycle progression depends on many factors. Cyclin-dependent kinase (CDK) inhibitor p21 (also known as p21(WAF1/Cip1)) is one of these factors that promote cell cycle arrest in response to a variety of stimuli. The inhibitory effect of P21 on cell cycle progression correlates with its nuclear localization. P21 can be induced by both p53-dependent and p53-independent mechanisms. Some other important functions attributed to p21 include transcriptional regulation, modulation or inhibition of apoptosis. These functions are largely dependent on direct p21/protein interactions and also on p21 subcellular localizations. In addition, p21 can play a role in DNA repair by interacting with proliferating cell nuclear antigen (PCNA). In this review, we will focus on the multiple functions of p21 in cell cycle regulation, apoptosis and gene transcription after DNA damage and briefly discuss the pathways and factors that have critical roles in p21 expression and activity.
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            The Roles of Autophagy in Cancer

            Autophagy is an intracellular degradative process that occurs under several stressful conditions, including organelle damage, the presence of abnormal proteins, and nutrient deprivation. The mechanism of autophagy initiates the formation of autophagosomes that capture degraded components and then fuse with lysosomes to recycle these components. The modulation of autophagy plays dual roles in tumor suppression and promotion in many cancers. In addition, autophagy regulates the properties of cancer stem-cells by contributing to the maintenance of stemness, the induction of recurrence, and the development of resistance to anticancer reagents. Although some autophagy modulators, such as rapamycin and chloroquine, are used to regulate autophagy in anticancer therapy, since this process also plays roles in both tumor suppression and promotion, the precise mechanism of autophagy in cancer requires further study. In this review, we will summarize the mechanism of autophagy under stressful conditions and its roles in tumor suppression and promotion in cancer and in cancer stem-cells. Furthermore, we discuss how autophagy is a promising potential therapeutic target in cancer treatment.
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              ABC transporters in cancer: more than just drug efflux pumps.

              Multidrug transporter proteins are best known for their contributions to chemoresistance through the efflux of anticancer drugs from cancer cells. However, a considerable body of evidence also points to their importance in cancer extending beyond drug transport to fundamental roles in tumour biology. Currently, much of the evidence for these additional roles is correlative and definitive studies are needed to confirm causality. We propose that delineating the precise roles of these transporters in tumorigenesis and treatment response will be important for the development of more effective targeted therapies.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                06 August 2020
                August 2020
                : 21
                : 16
                : 5622
                Affiliations
                [1 ]Department of Pharmacognosy, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi 75270, Pakistan; salmanahmed@ 123456uok.edu.pk
                [2 ]Department of Pharmacy, Abdul Wali Khan University, Mardan 23200, Pakistan; haroonkhan@ 123456awkum.edu.pk
                [3 ]Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10463, USA; michael.aschner@ 123456einsteinmed.org
                [4 ]Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan 8715973474, Iran; mirzaeih911h@ 123456mums.ac.ir
                [5 ]Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Etiler, 06330 Ankara, Turkey; esrak@ 123456gazi.edu.tr
                [6 ]Department of Agricultural Sciences, University of Naples Federico II, Via Università 100, 80055 Portici, Italy
                Author notes
                [* ]Correspondence: rafcapas@ 123456unina.it ; Tel.: +39-081-678664
                Author information
                https://orcid.org/0000-0003-2033-0181
                https://orcid.org/0000-0002-5829-7869
                https://orcid.org/0000-0002-3335-1822
                Article
                ijms-21-05622
                10.3390/ijms21165622
                7460698
                32781533
                051640cb-436e-43b3-998a-7b77680bbb9b
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 09 July 2020
                : 03 August 2020
                Categories
                Review

                Molecular biology
                furanocoumarin,apoptosis,autophagy,metastasis,cell cycle arrest
                Molecular biology
                furanocoumarin, apoptosis, autophagy, metastasis, cell cycle arrest

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