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      Mustard Seed ( Brassica nigra) Extract Exhibits Antiproliferative Effect against Human Lung Cancer Cells through Differential Regulation of Apoptosis, Cell Cycle, Migration, and Invasion

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          Abstract

          Lung cancer is the primary cause of cancer-related death worldwide, and development of novel lung cancer preventive and therapeutic agents are urgently needed. Brassica nigra (black mustard) seeds are commonly consumed in several Asian and African countries. Mustard seeds previously exhibited significant anticancer activities against several cancer types. In the present study, we have investigated various cellular and molecular mechanisms of anticancer effects of an ethanolic extract of B. nigra seeds against A549 and H1299 human non-small cell lung cancer cell lines. B. nigra extract showed a substantial growth-inhibitory effect as it reduced the viability and clonogenic survival of A549 and H1299 cells in a concentration-dependent manner. B. nigra extract induced cellular apoptosis in a time- and concentration-dependent fashion as evidenced from increased caspase-3 activity. Furthermore, treatment of both A549 and H1299 cells with B. nigra extract alone or in combination with camptothecin induced DNA double-strand breaks as evidenced by upregulation of γH2A histone family member X, Fanconi anemia group D2 protein, Fanconi anemia group J protein, ataxia-telangiectesia mutated and Rad3-related protein. Based on cell cycle analysis, B. nigra extract significantly arrested A549 and H1299 cells at S and G2/M phases. Additionally, B. nigra extract suppressed the migratory and invasive properties of both cell lines, downregulated the expression of matrix metalloproteinase-2 (MMP2), MMP9, and Snail and upregulated the expression of E-cadherin at mRNA and protein levels. Taken together, these findings indicate that B. nigra seed extract may have an important anticancer potential against human lung cancer which could be mediated through simultaneous and differential regulation of proliferation, apoptosis, DNA damage, cell cycle, migration, and invasion.

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          How the fanconi anemia pathway guards the genome.

          Fanconi Anemia (FA) is an inherited genomic instability disorder, caused by mutations in genes regulating replication-dependent removal of interstrand DNA crosslinks. The Fanconi Anemia pathway is thought to coordinate a complex mechanism that enlists elements of three classic DNA repair pathways, namely homologous recombination, nucleotide excision repair, and mutagenic translesion synthesis, in response to genotoxic insults. To this end, the Fanconi Anemia pathway employs a unique nuclear protein complex that ubiquitinates FANCD2 and FANCI, leading to formation of DNA repair structures. Lack of obvious enzymatic activities among most FA members has made it challenging to unravel its precise modus operandi. Here we review the current understanding of how the Fanconi Anemia pathway components participate in DNA repair and discuss the mechanisms that regulate this pathway to ensure timely, efficient, and correct restoration of chromosomal integrity.
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            Multi-targeted prevention of cancer by sulforaphane.

            Isothiocyanates are found in cruciferous vegetables such as broccoli, Brussels sprouts, cauliflower, and cabbage. Epidemiologic studies suggest that cruciferous vegetable intake may lower overall cancer risk, including colon and prostate cancer. Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables and is especially high in broccoli and broccoli sprouts. SFN has proved to be an effective chemoprotective agent in cell culture, carcinogen-induced and genetic animal cancer models, as well as in xenograft models of cancer. Early research focused on the "blocking activity" of SFN via Phase 2 enzyme induction, as well as inhibition of enzymes involved in carcinogen activation, but there has been growing interest in other mechanisms of chemoprotection by SFN. Recent studies suggest that SFN offers protection against tumor development during the "post-initiation" phase and mechanisms for suppression effects of SFN, including cell cycle arrest and apoptosis induction are of particular interest. In humans, a key factor in determining the efficacy of SFN as a chemoprevention agent is gaining an understanding of the metabolism, distribution and bioavailability of SFN and the factors that alter these parameters. This review discusses the established anti-cancer properties of SFN, with an emphasis on the possible chemoprevention mechanisms. The current status of SFN in human clinical trials also is included, with consideration of the chemistry, metabolism, absorption and factors influencing SFN bioavailability.
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              One hundred years of lung cancer.

              A hundred years ago, lung cancer was a reportable disease, and it is now the commonest cause of death from cancer in both men and women in the developed world, and before long, will reach that level in the developing world as well. The disease has no particular symptoms or signs for its detection at an early stage. Most patients therefore present with advanced stage IIIB or IV disease. Screening tests began in the 1950s with annual chest x-ray films and sputum cytology but they resulted in no improvement in overall mortality compared with control subjects. The same question is now being asked of spiral low-dose computed tomographic scanning. There have been big refinements in the staging classification of lung cancer and advances in stage identification using minimally invasive technology. Postsurgical mortality has declined from the early days of the 1950s but 5-year cure rates have only barely improved. The addition of chemotherapy to radical radiotherapy, together with novel radiotherapy techniques, is gradually improving the outcome for locally advanced, inoperable non-small cell lung cancer. Chemotherapy offers modest survival improvement for patients with non-small cell lung cancer, the modern agents being better tolerated resulting in an improved quality of life. The management of small cell lung cancer, which appeared so promising at the beginning of the 1970s, has hit a plateau with very little advance in outcome over the last 15 years. The most important and cost-effective management for lung cancer is smoking cessation, but for those with the disease, novel agents and treatment approaches are urgently needed.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                29 April 2020
                May 2020
                : 25
                : 9
                : 2069
                Affiliations
                [1 ]Department of Pathology, Chonbuk National University Medical School, Jeonju 54907, Korea; asmaascience3@ 123456gmail.com (A.G.A.); usamahussein@ 123456jbnu.ac.kr (U.K.H.); kmkim@ 123456jbnu.ac.kr (K.M.K.)
                [2 ]Department of Biotechnology and Life Sciences, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef 62511, Egypt; amreahmed@ 123456psas.bsu.edu.eg
                [3 ]Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju 54907, Korea
                [4 ]Faculty of Science, Beni-Suef University, Beni-Suef 62511, Egypt; mhmada@ 123456aucegypt.edu (H.M.M.); ola.hammouda@ 123456gmail.com (O.H.)
                [5 ]Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
                Author notes
                [* ]Correspondence: kyjang@ 123456chonbuk.ac.kr (K.Y.J.); abishayee@ 123456lecom.edu or abishayee@ 123456gmail.com (A.B.); Tel.: +82-10-4228-9970 (K.Y.J.); +1-941-782-5950 (A.B.)
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-0628-4422
                https://orcid.org/0000-0002-5276-4446
                https://orcid.org/0000-0001-9159-960X
                Article
                molecules-25-02069
                10.3390/molecules25092069
                7248788
                32365503
                511a5d03-c0d7-40bb-839e-5ac480fc7e6f
                © 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
                : 12 March 2020
                : 26 April 2020
                Categories
                Article

                brassica nigra,lung cancer,proliferation,dna damage,apoptosis

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