Iron Metabolism as a Potential Mechanism for Inducing TRAIL-Mediated Extrinsic Apoptosis Using Methylsulfonylmethane in Embryonic Cancer Stem Cells

Embryonic cancer stem cells (CSCs) can differentiate into any cancer type. Targeting CSC using natural compounds is a good approach as it suppresses cancer recurrence with fewer adverse effects, and methylsulfonylmethane (MSM) is a sulfur-containing compound with well-known anticancer activities. Th...

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Autores principales: Nipin Sp, Dong Young Kang, Eun Seong Jo, Jin-Moo Lee, Kyoung-Jin Jang
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Lenguaje:EN
Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/a0a4ab7c9a02459785ba33a8b63fe61b
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spelling oai:doaj.org-article:a0a4ab7c9a02459785ba33a8b63fe61b2021-11-25T17:07:53ZIron Metabolism as a Potential Mechanism for Inducing TRAIL-Mediated Extrinsic Apoptosis Using Methylsulfonylmethane in Embryonic Cancer Stem Cells10.3390/cells101128472073-4409https://doaj.org/article/a0a4ab7c9a02459785ba33a8b63fe61b2021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2847https://doaj.org/toc/2073-4409Embryonic cancer stem cells (CSCs) can differentiate into any cancer type. Targeting CSC using natural compounds is a good approach as it suppresses cancer recurrence with fewer adverse effects, and methylsulfonylmethane (MSM) is a sulfur-containing compound with well-known anticancer activities. This study determined the mechanistic aspects of the anticancer activity of MSM. We used Western blotting and real-time qPCR for molecular signaling studies and conducted flow cytometry for analyzing the processes in cells. Our results suggested an inhibition in the expression of CSC markers and Wnt/β-catenin signaling. MSM induced TRAIL-mediated extrinsic apoptosis in NCCIT and NTERA-2 cells rather than an intrinsic pathway. Inhibition of iron metabolism-dependent reactive oxygen species (ROS) generation takes part in TRAIL-mediated apoptosis induction by MSM. Suppressing iron metabolism by MSM also regulated p38/p53/ERK signaling and microRNA expressions, such as upregulating miR-130a and downregulating miR-221 and miR-222, which resulted in TRAIL induction and thereby extrinsic pathway of apoptosis. Hence, MSM could be a good candidate for neoadjuvant therapy by targeting CSCs by inhibiting iron metabolism.Nipin SpDong Young KangEun Seong JoJin-Moo LeeKyoung-Jin JangMDPI AGarticleNCCITNTERA-2MSMTRAILiron metabolismp38/p53/ERK signalingBiology (General)QH301-705.5ENCells, Vol 10, Iss 2847, p 2847 (2021)
institution DOAJ
collection DOAJ
language EN
topic NCCIT
NTERA-2
MSM
TRAIL
iron metabolism
p38/p53/ERK signaling
Biology (General)
QH301-705.5
spellingShingle NCCIT
NTERA-2
MSM
TRAIL
iron metabolism
p38/p53/ERK signaling
Biology (General)
QH301-705.5
Nipin Sp
Dong Young Kang
Eun Seong Jo
Jin-Moo Lee
Kyoung-Jin Jang
Iron Metabolism as a Potential Mechanism for Inducing TRAIL-Mediated Extrinsic Apoptosis Using Methylsulfonylmethane in Embryonic Cancer Stem Cells
description Embryonic cancer stem cells (CSCs) can differentiate into any cancer type. Targeting CSC using natural compounds is a good approach as it suppresses cancer recurrence with fewer adverse effects, and methylsulfonylmethane (MSM) is a sulfur-containing compound with well-known anticancer activities. This study determined the mechanistic aspects of the anticancer activity of MSM. We used Western blotting and real-time qPCR for molecular signaling studies and conducted flow cytometry for analyzing the processes in cells. Our results suggested an inhibition in the expression of CSC markers and Wnt/β-catenin signaling. MSM induced TRAIL-mediated extrinsic apoptosis in NCCIT and NTERA-2 cells rather than an intrinsic pathway. Inhibition of iron metabolism-dependent reactive oxygen species (ROS) generation takes part in TRAIL-mediated apoptosis induction by MSM. Suppressing iron metabolism by MSM also regulated p38/p53/ERK signaling and microRNA expressions, such as upregulating miR-130a and downregulating miR-221 and miR-222, which resulted in TRAIL induction and thereby extrinsic pathway of apoptosis. Hence, MSM could be a good candidate for neoadjuvant therapy by targeting CSCs by inhibiting iron metabolism.
format article
author Nipin Sp
Dong Young Kang
Eun Seong Jo
Jin-Moo Lee
Kyoung-Jin Jang
author_facet Nipin Sp
Dong Young Kang
Eun Seong Jo
Jin-Moo Lee
Kyoung-Jin Jang
author_sort Nipin Sp
title Iron Metabolism as a Potential Mechanism for Inducing TRAIL-Mediated Extrinsic Apoptosis Using Methylsulfonylmethane in Embryonic Cancer Stem Cells
title_short Iron Metabolism as a Potential Mechanism for Inducing TRAIL-Mediated Extrinsic Apoptosis Using Methylsulfonylmethane in Embryonic Cancer Stem Cells
title_full Iron Metabolism as a Potential Mechanism for Inducing TRAIL-Mediated Extrinsic Apoptosis Using Methylsulfonylmethane in Embryonic Cancer Stem Cells
title_fullStr Iron Metabolism as a Potential Mechanism for Inducing TRAIL-Mediated Extrinsic Apoptosis Using Methylsulfonylmethane in Embryonic Cancer Stem Cells
title_full_unstemmed Iron Metabolism as a Potential Mechanism for Inducing TRAIL-Mediated Extrinsic Apoptosis Using Methylsulfonylmethane in Embryonic Cancer Stem Cells
title_sort iron metabolism as a potential mechanism for inducing trail-mediated extrinsic apoptosis using methylsulfonylmethane in embryonic cancer stem cells
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/a0a4ab7c9a02459785ba33a8b63fe61b
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AT dongyoungkang ironmetabolismasapotentialmechanismforinducingtrailmediatedextrinsicapoptosisusingmethylsulfonylmethaneinembryoniccancerstemcells
AT eunseongjo ironmetabolismasapotentialmechanismforinducingtrailmediatedextrinsicapoptosisusingmethylsulfonylmethaneinembryoniccancerstemcells
AT jinmoolee ironmetabolismasapotentialmechanismforinducingtrailmediatedextrinsicapoptosisusingmethylsulfonylmethaneinembryoniccancerstemcells
AT kyoungjinjang ironmetabolismasapotentialmechanismforinducingtrailmediatedextrinsicapoptosisusingmethylsulfonylmethaneinembryoniccancerstemcells
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