Iridin Induces G2/M Phase Cell Cycle Arrest and Extrinsic Apoptotic Cell Death through PI3K/AKT Signaling Pathway in AGS Gastric Cancer Cells

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Abstract

Iridin is a natural flavonoid found in Belamcanda chinensis documented for its broad spectrum of biological activities like antioxidant, antitumor, and antiproliferative effects. In the present study, we have investigated the antitumor potential of iridin in AGS gastric cancer cells. Iridin treatment decreases AGS cell growth and promotes G2/M phase cell cycle arrest by attenuating the expression of Cdc25C, CDK1, and Cyclin B1 proteins. Iridin-treatment also triggered apoptotic cell death in AGS cells, which was verified by cleaved Caspase-3 (Cl- Caspase-3) and poly ADP-ribose polymerase (PARP) protein expression. Further apoptotic cell death was confirmed by increased apoptotic cell death fraction shown in allophycocyanin (APC)/Annexin V and propidium iodide staining. Iridin also increased the expression of extrinsic apoptotic pathway proteins like Fas, FasL, and cleaved Caspase-8 in AGS cells. On the contrary, iridin-treated AGS cells did not show variations in proteins related to an intrinsic apoptotic pathway such as Bax and Bcl-xL. Besides, Iridin showed inhibition of PI3K/AKT signaling pathways by downregulation of (p-PI3K, p-AKT) proteins in AGS cells. In conclusion, these data suggest that iridin has anticancer potential by inhibiting PI3K/AKT pathway. It could be a basis for further drug design in gastric cancer treatment.

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Cell death: a review of the major forms of apoptosis, necrosis and autophagy

Mark D’Arcy (2019)

Cell death was once believed to be the result of one of two distinct processes, apoptosis (also known as programmed cell death) or necrosis (uncontrolled cell death); in recent years, however, several other forms of cell death have been discovered highlighting that a cell can die via a number of differing pathways. Apoptosis is characterised by a number of characteristic morphological changes in the structure of the cell, together with a number of enzyme-dependent biochemical processes. The result being the clearance of cells from the body, with minimal damage to surrounding tissues. Necrosis, however, is generally characterised to be the uncontrolled death of the cell, usually following a severe insult, resulting in spillage of the contents of the cell into surrounding tissues and subsequent damage thereof. Failure of apoptosis and the resultant accumulation of damaged cells in the body can result in various forms of cancer. An understanding of the pathways is therefore important in developing efficient chemotherapeutics. It has recently become clear that there exists a number of subtypes of apoptosis and that there is an overlap between apoptosis, necrosis and autophagy. The goal of this review is to provide a general overview of the current knowledge relating to the various forms of cell death, including apoptosis, necrosis, oncosis, pyroptosis and autophagy. This will provide researchers with a summary of the major forms of cell death and allow them to compare and contrast between them.

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Apoptosis in cancer: from pathogenesis to treatment

Rebecca SY Wong (2011)

Apoptosis is an ordered and orchestrated cellular process that occurs in physiological and pathological conditions. It is also one of the most studied topics among cell biologists. An understanding of the underlying mechanism of apoptosis is important as it plays a pivotal role in the pathogenesis of many diseases. In some, the problem is due to too much apoptosis, such as in the case of degenerative diseases while in others, too little apoptosis is the culprit. Cancer is one of the scenarios where too little apoptosis occurs, resulting in malignant cells that will not die. The mechanism of apoptosis is complex and involves many pathways. Defects can occur at any point along these pathways, leading to malignant transformation of the affected cells, tumour metastasis and resistance to anticancer drugs. Despite being the cause of problem, apoptosis plays an important role in the treatment of cancer as it is a popular target of many treatment strategies. The abundance of literature suggests that targeting apoptosis in cancer is feasible. However, many troubling questions arise with the use of new drugs or treatment strategies that are designed to enhance apoptosis and critical tests must be passed before they can be used safely in human subjects.

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Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies

Giuseppa Pistritto, Daniela Trisciuoglio, Claudia Ceci … (2016)

Apoptosis is a form of programmed cell death that results in the orderly and efficient removal of damaged cells, such as those resulting from DNA damage or during development. Apoptosis can be triggered by signals from within the cell, such as genotoxic stress, or by extrinsic signals, such as the binding of ligands to cell surface death receptors. Deregulation in apoptotic cell death machinery is an hallmark of cancer. Apoptosis alteration is responsible not only for tumor development and progression but also for tumor resistance to therapies. Most anticancer drugs currently used in clinical oncology exploit the intact apoptotic signaling pathways to trigger cancer cell death. Thus, defects in the death pathways may result in drug resistance so limiting the efficacy of therapies. Therefore, a better understanding of the apoptotic cell death signaling pathways may improve the efficacy of cancer therapy and bypass resistance. This review will highlight the role of the fundamental regulators of apoptosis and how their deregulation, including activation of anti-apoptotic factors (i.e., Bcl-2, Bcl-xL, etc) or inactivation of pro-apoptotic factors (i.e., p53 pathway) ends up in cancer cell resistance to therapies. In addition, therapeutic strategies aimed at modulating apoptotic activity are briefly discussed.

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Author and article information

Contributors

H.P. Vasantha Rupasinghe: Role: Academic Editor

Maurizio Battino: Role: Academic Editor

Journal

Journal ID (nlm-ta): Molecules

Journal ID (iso-abbrev): Molecules

Journal ID (publisher-id): molecules

Title: Molecules

Publisher: MDPI

ISSN (Electronic): 1420-3049

Publication date (Electronic): 10 May 2021

Publication date Collection: May 2021

Volume: 26

Issue: 9

Electronic Location Identifier: 2802

Affiliations

[1 ]Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Gazwa, Jinju 52828, Korea; shelake.pritam@ 123456gmail.com (P.-B.B.); preethivetrivel05@ 123456gmail.com (P.V.); sangdis2@ 123456naver.com (S.-E.H.); shark159753@ 123456naver.com (H.-H.K.); wonck@ 123456gnu.ac.kr (C.-K.W.)

[2 ]Biological Resources Research Group, Bioenvironmental Science & Toxicology Division, Korea Institute of Toxicology (KIT), 17 Jeigok-gil, Jinju 52834, Korea; jdher@ 123456kitox.re.kr

Author notes

[* ]Correspondence: ksm4234@ 123456gnu.ac.kr (S.-M.K.); gonskim@ 123456gnu.ac.kr (G.-S.K.); Tel.: +82-10-3834-5823 (G.-S.K.)

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Pritam-Bhagwan Bhosale https://orcid.org/0000-0003-1691-7844

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Publisher ID: molecules-26-02802

DOI: 10.3390/molecules26092802

PMC ID: 8126061

PubMed ID: 34068568

SO-VID: fd73c118-9b66-4c37-84a9-f65072028ad5

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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 ( https://creativecommons.org/licenses/by/4.0/).

Iridin Induces G2/M Phase Cell Cycle Arrest and Extrinsic Apoptotic Cell Death through PI3K/AKT Signaling Pathway in AGS Gastric Cancer Cells

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Karger: Oncology

Most cited references 45

Cell death: a review of the major forms of apoptosis, necrosis and autophagy

Apoptosis in cancer: from pathogenesis to treatment

Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies

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