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      Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

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          Abstract

          Doxorubicin (DOX) is a well-known chemotherapeutic agent extensively applied in the field of cancer therapy. However, similar to other chemotherapeutic agents such as cisplatin, paclitaxel, docetaxel, etoposide and oxaliplatin, cancer cells are able to obtain chemoresistance that limits DOX efficacy. In respect to dose-dependent side effect of DOX, enhancing its dosage is not recommended for effective cancer chemotherapy. Therefore, different strategies have been considered for reversing DOX resistance and diminishing its side effects. Phytochemical are potential candidates in this case due to their great pharmacological activities. Curcumin is a potential antitumor phytochemical isolated from Curcuma longa with capacity of suppressing cancer metastasis and proliferation and affecting molecular pathways. Experiments have demonstrated the potential of curcumin for inhibiting chemoresistance by downregulating oncogene pathways such as MMP-2, TGF-β, EMT, PI3K/Akt, NF-κB and AP-1. Furthermore, coadministration of curcumin and DOX potentiates apoptosis induction in cancer cells. In light of this, nanoplatforms have been employed for codelivery of curcumin and DOX. This results in promoting the bioavailability and internalization of the aforementioned active compounds in cancer cells and, consequently, enhancing their antitumor activity. Noteworthy, curcumin has been applied for reducing adverse effects of DOX on normal cells and tissues via reducing inflammation, oxidative stress and apoptosis. The current review highlights the anticancer mechanism, side effects and codelivery of curcumin and DOX via nanovehicles.

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          Most cited references242

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            The basics of epithelial-mesenchymal transition.

            The origins of the mesenchymal cells participating in tissue repair and pathological processes, notably tissue fibrosis, tumor invasiveness, and metastasis, are poorly understood. However, emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) represent one important source of these cells. As we discuss here, processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias. The identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions.
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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                11 November 2020
                November 2020
                : 12
                : 11
                : 1084
                Affiliations
                [1 ]Faculty of Engineering and Natural Sciences, Sabanci University, Orta Mahalle, Üniversite Caddesi No. 27, Orhanlı, Tuzla, 34956 Istanbul, Turkey; milad.ashrafizadeh@ 123456sabanciuniv.edu
                [2 ]Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla, 34956, Istanbul, Turkey; alizarrabi@ 123456sabanciuniv.edu
                [3 ]Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran 1419963114, Iran; faridhashemi172@ 123456gmail.com
                [4 ]Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran 1916893813, Iran; ah_zabolian@ 123456student.iautmu.ac.ir (A.Z.); h.saleki@ 123456student.iautmu.ac.ir (H.S.); morteza1429@ 123456gmail.com (M.B.); negarazami77@ 123456gmail.com (N.A.); atefe.kazemzade1376@ 123456gmail.com (A.K.B.)
                [5 ]Department of Food Hygiene and Quality Control, Division of Epidemiology & Zoonoses, Faculty of Veterinary Medicine, University of Tehran, Tehran 1419963114, Iran; houshmandi.kia7@ 123456ut.ac.ir
                [6 ]Cancer Science Institute of Singapore and Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore; e0336095@ 123456u.nus.edu
                [7 ]Centre for Micro-BioRobotics, Istituto Italiano di Tecnologia, viale Rinaldo Piaggio 34, 56,025 Pontedera, Pisa, Italy
                [8 ]Department of Pharmacy, Abdul Wali Khan University, Mardan 23200, Pakistan; haroonkhan@ 123456awkum.edu.pk
                Author notes
                [* ]Correspondence: pooyan.makvandi@ 123456iit.it (P.M.); csiapk@ 123456nus.edu.sg (A.P.K.); Tel.: +39-392-828-8866 (P.M.); +65-6516-5456 (A.P.K.)
                [†]

                These authors have contributed equally.

                Author information
                https://orcid.org/0000-0001-6605-822X
                https://orcid.org/0000-0003-0391-1769
                https://orcid.org/0000-0001-9901-9534
                https://orcid.org/0000-0003-2456-0961
                https://orcid.org/0000-0002-3754-5712
                Article
                pharmaceutics-12-01084
                10.3390/pharmaceutics12111084
                7697177
                33187385
                2c74d45d-02be-48ef-b656-a13802210290
                © 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
                : 03 October 2020
                : 07 November 2020
                Categories
                Review

                doxorubicin,curcumin,chemoresistance,side effect,apoptosis,nanodelivery

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