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      Moringa oleifera and Musa sapientum ameliorated 7,12-Dimethylbenz[a]anthracene-induced upregulations of Ki67 and multidrug resistance 1 genes in rats

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          Abstract

          Objectives:

          Moringa oleifera (MO) and Musa sapientum (MS) are plants of ethnomedicinal importance. We evaluated the effects of MOF6 (extracted from MO leaves) and MSF1 (extracted from MS suckers) on immunomodulations of Ki67 (proliferation biomarker) and multidrug resistance 1 (MDR1) genes in the liver of rats in 7,12-Dimethylbenz[a]anthracene (DMBA)-induced hepatotoxicity and mutagenesis to determine their antiproliferation, anti-drug resistance, and anticancer potentials.

          Methods:

          Forty-five adult male rats were randomly divided into nine groups ( n = 5). Groups 1 and 2 received physiological saline and 15 mg/kg bodyweight of DMBA, respectively. Groups 3 and 4 received 15 mg/kg bodyweight DMBA and were treated with 15 and 30 mg/kg bodyweight of MOF6, respectively. Group 5 received 15 mg/kg bodyweight DMBA and was treated with 10 mg/kg bodyweight of MSF1. Group 6 received 15 mg/kg bodyweight DMBA and was treated with 3.35 mg/kg bodyweight of doxorubicin and intravenous injection of 0.5 ml/200 g of cisplatin. Groups 7–9 received only 15 and 30 mg/kg bodyweight of MOF6 and 10 mg/kg bodyweight of MSF1, respectively. DMBA, doxorubicin, and extracts doses were administered orally. The duration of our experimental procedure was 8 weeks. Consequently, liver histopathology (hematoxylin and eosin technique) and enzyme-linked immunosorbent assay homogenates’ concentrations of Ki67 and MDR1 were evaluated. Computed data were statistically analyzed ( P ≤ 0.05).

          Results:

          Results showed normal histoarchitectures of the liver in all groups. Statistical analyses showed significant ( P ≤ 0.05) and non-significant decreased concentrations ( P ≥ 0.05) of Ki67 and MDR1 in Groups 3–9 compared with Group 2. Therefore, MOF6 and MSF1 ameliorated DMBA-induced hepatotoxicity, abnormal proliferation, and drug resistance.

          Conclusion:

          MOF6 and MSF1 possess antiproliferation, anti-drug resistance, and anticancer potentials.

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          Most cited references23

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          The Ki-67 protein: from the known and the unknown.

          T Scholzen, J. Gerdes (2000)
          The expression of the human Ki-67 protein is strictly associated with cell proliferation. During interphase, the antigen can be exclusively detected within the nucleus, whereas in mitosis most of the protein is relocated to the surface of the chromosomes. The fact that the Ki-67 protein is present during all active phases of the cell cycle (G(1), S, G(2), and mitosis), but is absent from resting cells (G(0)), makes it an excellent marker for determining the so-called growth fraction of a given cell population. In the first part of this study, the term proliferation marker is discussed and examples of the applications of anti-Ki-67 protein antibodies in diagnostics of human tumors are given. The fraction of Ki-67-positive tumor cells (the Ki-67 labeling index) is often correlated with the clinical course of the disease. The best-studied examples in this context are carcinomas of the prostate and the breast. For these types of tumors, the prognostic value for survival and tumor recurrence has repeatedly been proven in uni- and multivariate analysis. The preparation of new monoclonal antibodies that react with the Ki-67 equivalent protein from rodents now extends the use of the Ki-67 protein as a proliferation marker to laboratory animals that are routinely used in basic research. The second part of this review focuses on the biology of the Ki-67 protein. Our current knowledge of the Ki-67 gene and protein structure, mRNA splicing, expression, and cellular localization during the cell-division cycle is summarized and discussed. Although the Ki-67 protein is well characterized on the molecular level and extensively used as a proliferation marker, the functional significance still remains unclear. There are indications, however, that Ki-67 protein expression is an absolute requirement for progression through the cell-division cycle. Copyright 2000 Wiley-Liss, Inc.
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            The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells?

            Vicki Plaks, Niwen Kong, Zena Werb (2015)
            Cancer stem cells (CSCs) are tumor cells that have the principal properties of self-renewal, clonal tumor initiation capacity, and clonal long-term repopulation potential. CSCs reside in niches, which are anatomically distinct regions within the tumor microenvironment. These niches maintain the principle properties of CSCs, preserve their phenotypic plasticity, protect them from the immune system, and facilitate their metastatic potential. In this perspective, we focus on the CSC niche and discuss its contribution to tumor initiation and progression. Since CSCs survive many commonly employed cancer therapies, we examine the prospects of targeting the niche components as preferable therapeutic targets.
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              Current Strategies for Brain Drug Delivery

              Xiaowei Dong (2018)
              The blood-brain barrier (BBB) has been a great hurdle for brain drug delivery. The BBB in healthy brain is a diffusion barrier essential for protecting normal brain function by impeding most compounds from transiting from the blood to the brain; only small molecules can cross the BBB. Under certain pathological conditions of diseases such as stroke, diabetes, seizures, multiple sclerosis, Parkinson's disease and Alzheimer disease, the BBB is disrupted. The objective of this review is to provide a broad overview on current strategies for brain drug delivery and related subjects from the past five years. It is hoped that this review could inspire readers to discover possible approaches to deliver drugs into the brain. After an initial overview of the BBB structure and function in both healthy and pathological conditions, this review re-visits, according to recent publications, some questions that are controversial, such as whether nanoparticles by themselves could cross the BBB and whether drugs are specifically transferred to the brain by actively targeted nanoparticles. Current non-nanoparticle strategies are also reviewed, such as delivery of drugs through the permeable BBB under pathological conditions and using non-invasive techniques to enhance brain drug uptake. Finally, one particular area that is often neglected in brain drug delivery is the influence of aging on the BBB, which is captured in this review based on the limited studies in the literature.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Health Sci (Qassim)
                Journal ID (iso-abbrev): Int J Health Sci (Qassim)
                Title: International Journal of Health Sciences
                Publisher: Qassim Uninversity (Saudi Arabia )
                ISSN (Print): 1658-3639
                ISSN (Electronic): 1658-7774
                Publication date (Print): May-Jun 2021
                Volume: 15
                Issue: 3
                Pages: 26-33
                Affiliations
                [1 ]Department of Anatomy, Faculty of Basic Medical Sciences, Olabisi Onabanjo University, Ogun State, Nigeria
                [2 ]Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Kwara State, Nigeria
                [3 ]Department of Chemistry, Faculty of Physical Sciences, University of Ilorin, Ilorin, Kwara State, Nigeria
                [4 ]Department of Anatomy, Faculty of Basic Medical Sciences, Ekiti State University, Ado-Ekiti, Ekiti State, Nigeria
                Author notes
                Address for correspondence: Dr. A. A. Akinlolu, Department of Anatomy, Faculty of Basic Medical Sciences, Olabisi Onabanjo University, Ogun State, Nigeria. Phone: +2348062765308. E-mail: adelaja.akinlolu.454@ 123456my.csun.edu
                Article
                Publisher ID: IJHS-15-26
                PMC ID: 8220645
                PubMed ID: 34234633
                SO-VID: 661305e6-d2b0-40a2-bddd-d7da3966bc80
                Copyright © Copyright: © International Journal of Health Sciences
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Subject: Original Article

                Keywords: 7,12-dimethylbenz[a]anthracene,ki67,moringa oleifera,multidrug resistance 1,musa sapientum
                Data availability:
                Keywords: 7,12-dimethylbenz[a]anthracene, ki67, moringa oleifera, multidrug resistance 1, musa sapientum

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