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      Jaboticaba ( Myrciaria jaboticaba) peel extracts induce reticulum stress and apoptosis in breast cancer cells

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          Highlights

          • Ethyl acetate and water–ethanol extracts from Jaboticaba peel were assessed.

          • Both extracts inhibited the clonogenic potential of MDA-MB-231 breast cancer cells.

          • Ethyl acetate extract was more effective against MCF7 cells.

          • Extracts’ action mechanisms can be the induction of endoplasmic stress and apoptosis.

          Abstract

          Jaboticaba peel ( Myrciaria jaboticaba) is a source of bioactive compounds. We investigated the anticancer activity of ethyl acetate extract (JE1) and hydroethanolic extract (JE2) of Jaboticaba peel against breast cancer. Both JE1 and JE2 inhibited clonogenic potential of MDA-MB-231 cells while JE1 was particularly effective in MCF7 cells. Anchorage-independent growth and cell viability was also inhibited by JE1 and JE2. In addition to growth inhibition, JE1 and JE2 could also inhibit migration and invasion of cells. Interestingly, JE1 and JE2 show selective inhibition towards certain breast cancer cells and biological processes. Mechanistic evaluations showed that JE1 induced PARP cleavage, BAX and BIP indicating apoptotic induction. An elevation of phosphorylated ERK was observed in MCF7 cells in response to JE1 and JE2 along with increased IRE-α and CHOP expression indicating increased endoplasmic stress. Therefore, Jaboticaba peel extracts could be potentially considered for further development for breast cancer inhibition.

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          ERK signalling: a master regulator of cell behaviour, life and fate

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            CHOP is a multifunctional transcription factor in the ER stress response.

            The accumulation of unfolded proteins in the endoplasmic reticulum (ER) induces ER stress. To restore ER homeostasis, cells possess a highly specific ER quality-control system called the unfold protein response (UPR). In the case of prolonged ER stress or UPR malfunction, apoptosis signalling is activated. This ER stress-induced apoptosis has been implicated in the pathogenesis of several conformational diseases. CCAAT-enhancer-binding protein homologous protein (CHOP) is induced by ER stress and mediates apoptosis. Recent studies by the Gotoh group have shown that the CHOP pathway is also involved in ER stress-induced cytokine production in macrophages. The multifunctional roles of CHOP in the ER stress response are discussed below.
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              Anti-Cancer Natural Products and Their Bioactive Compounds Inducing ER Stress-Mediated Apoptosis: A Review

              Cancer is the second biggest cause of death worldwide. Despite a number of studies being conducted, the effective mechanism for treating cancer has not yet been fully understood. The tumor-microenvironment such as hypoxia, low nutrients could disturb function of endoplasmic reticulum (ER) to maintain cellular homeostasis, ultimately leading to the accumulation of unfolded proteins in ER, so-called ER stress. The ER stress has a close relation with cancer. ER stress initiates unfolded protein response (UPR) to re-establish ER homeostasis as an adaptive pathway in cancer. However, persistent ER stress triggers the apoptotic pathway. Therefore, blocking the adaptive pathway of ER stress or facilitating the apoptotic pathway could be an anti-cancer strategy. Recently, natural products and their derivatives have been reported to have anti-cancer effects via ER stress. Here, we address mechanisms of ER stress-mediated apoptosis and highlight strategies for cancer therapy by utilizing ER stress. Furthermore, we summarize anti-cancer activity of the natural products via ER stress in six major types of cancers globally (lung, breast, colorectal, gastric, prostate and liver cancer). This review deepens the understanding of ER stress mechanisms in major cancers as well as the suppressive impact of natural products against cancers via ER stress.
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                Author and article information

                Contributors
                Journal
                Food Chem (Oxf)
                Food Chem (Oxf)
                Food Chemistry: Molecular Sciences
                Elsevier
                2666-5662
                22 February 2023
                30 July 2023
                22 February 2023
                : 6
                : 100167
                Affiliations
                [a ]Nutrition Postgraduate Program, Department of Nutrition, Health Science Center, Federal University of Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte, Brazil
                [b ]Department of Oncology, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, United States
                [c ]Department of Food and Nutrition, School of Food Engineering, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
                Author notes
                [* ]Corresponding author at: Department of Nutrition, Health Science Center Federal University of Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte, Brazil. juliana.maia@ 123456ufrn.br
                Article
                S2666-5662(23)00007-2 100167
                10.1016/j.fochms.2023.100167
                9982605
                36875800
                03d60da7-7bb0-449b-8659-35384fc6840a
                © 2023 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 1 May 2022
                : 23 December 2022
                : 18 February 2023
                Categories
                Articles from the Special Issue ‘Polyphenols in the development of functional foods and impact on health and nutrition in South and Central Americas’ by Cinthia Betim and Lilian Mariutti

                antitumor,bioactive compounds,breast cancer,myrciaria jaboticaba

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