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      A Review of The Synergistic Effects of Curcumin with Proteasome Inhibitors in Multiple Myeloma Preclinical Models

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          Abstract

          Proteasome inhibitors are the cornerstone of multiple myeloma treatment, but challenges still remain despite the increased survival rates. We conducted a review on the role of curcumin, a natural product, as an adjunct to bortezomib and carfilzomib in preclinical multiple myeloma models. Four studies reviewed showed enhanced anticancer effects when curcumin was combined with bortezomib compared to either treatment alone. Two additional studies showed similar results with carfilzomib. Synergistic mechanisms include inhibition of NF-kB, IL-6-induced signaling pathways, JNK pathway modulation, and increased cell cycle arrest.

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          Curcumin: A Review of Its’ Effects on Human Health

          Susan J Hewlings, Douglas Kalman (2017)
          Turmeric, a spice that has long been recognized for its medicinal properties, has received interest from both the medical/scientific world and from culinary enthusiasts, as it is the major source of the polyphenol curcumin. It aids in the management of oxidative and inflammatory conditions, metabolic syndrome, arthritis, anxiety, and hyperlipidemia. It may also help in the management of exercise-induced inflammation and muscle soreness, thus enhancing recovery and performance in active people. In addition, a relatively low dose of the complex can provide health benefits for people that do not have diagnosed health conditions. Most of these benefits can be attributed to its antioxidant and anti-inflammatory effects. Ingesting curcumin by itself does not lead to the associated health benefits due to its poor bioavailability, which appears to be primarily due to poor absorption, rapid metabolism, and rapid elimination. There are several components that can increase bioavailability. For example, piperine is the major active component of black pepper and, when combined in a complex with curcumin, has been shown to increase bioavailability by 2000%. Curcumin combined with enhancing agents provides multiple health benefits. The purpose of this review is to provide a brief overview of the plethora of research regarding the health benefits of curcumin.
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            Multiple myeloma

            Shaji K Kumar, Vincent Rajkumar, Pieter Sonneveld … (2017)
            Multiple myeloma is a malignancy of terminally differentiated plasma cells, and patients typically present with bone marrow infiltration of clonal plasma cells and monoclonal protein in the serum and/or urine. The diagnosis of multiple myeloma is made when clear end-organ damage attributable to the plasma cell proliferative disorder or when findings that suggest a high likelihood of their development are present. Distinguishing symptomatic multiple myeloma that requires treatment from the precursor stages of monoclonal gammopathy of undetermined significance and smouldering multiple myeloma is important, as observation is the standard for those conditions. Much progress has been made over the past decade in the understanding of disease biology and individualized treatment approaches. Several new classes of drugs, such as proteasome inhibitors and immunomodulatory drugs, have joined the traditional armamentarium (corticosteroids, alkylating agents and anthracyclines) and, along with high-dose therapy and autologous haemopoietic stem cell transplantation, have led to deeper and durable clinical responses. Indeed, an increasing proportion of patients are achieving lasting remissions, raising the possibility of cure for this disease. Success will probably depend on using combinations of effective agents and treating patients in the early stages of disease, such as patients with smouldering multiple myeloma.
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              Proteasome inhibitors in cancer therapy

              Elisabet Manasanch, Robert Orlowski (2017)
              By preventing the accumulation of misfolded or damaged proteins, the ubiquitin-proteasome pathway has essential functions in cell homeostasis. Cancer cells produce proteins that promote cell survival and proliferation, and inhibit cell death, and thus, clinical trials have tested the therapeutic effect of proteasome inhibitors on patients with a variety of cancer types, mainly haematological malignancies. Herein, the authors discuss the advances and challenges derived from the introduction of proteasome inhibitors in the clinic, including therapeutic resistance.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Integr Cancer Ther
                Journal ID (iso-abbrev): Integr Cancer Ther
                Journal ID (publisher-id): ICT
                Journal ID (hwp): spict
                Title: Integrative Cancer Therapies
                Publisher: SAGE Publications (Sage CA: Los Angeles, CA )
                ISSN (Print): 1534-7354
                ISSN (Electronic): 1552-695X
                Publication date (Electronic): 6 March 2023
                Publication date Collection: 2023
                Volume: 22
                Electronic Location Identifier: 15347354231159322
                Affiliations
                [1 ]University of Arizona, Tucson, AZ, USA
                [2 ]University of Arizona, Phoenix, AZ, USA
                Author notes
                [*]Shaunak K. Pandya, Department of Hematology-Oncology, University of Arizona, 1501 N Campbell Ave, Tucson, AZ 85724, USA. Email: skpandya@ 123456arizona.edu
                Author information
                https://orcid.org/0000-0002-5495-733X
                Article
                Publisher ID: 10.1177_15347354231159322
                DOI: 10.1177/15347354231159322
                PMC ID: 9996714
                PubMed ID: 36879488
                SO-VID: 786ba197-d76b-4da8-a4aa-e5d831829838
                Copyright © © The Author(s) 2023
                License:

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                Date received : 22 November 2022
                Date revision received : 13 January 2023
                Date accepted : 3 February 2023
                Categories
                Subject: Review Article
                Custom metadata
                cover-date January-December 2023
                typesetter ts1

                Keywords: curcumin,multiple myeloma,bortezomib,carfilzomib
                Data availability:
                Keywords: curcumin, multiple myeloma, bortezomib, carfilzomib

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