Compound K Promotes Megakaryocytic Differentiation by NLRP3 Inflammasome Activation

Platelets are essential blood components that maintain hemostasis, prevent excessive bleeding, and facilitate wound healing. Reduced platelet counts are implicated in various diseases, including leukemia, hepatitis, cancer, and Alzheimer’s disease. Enhancing megakaryocytic differentiation is a promi...

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Main Authors: Seonhwa Hwang, Min-Seo Park, Anthony Junhoe Koo, Eunsoo Yoo, Seh-Hyon Song, Hye-Kyung Kim, Min-Hi Park, Jae-Seon Kang
Format: Article
Language:English
Published: MDPI AG 2024-10-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/14/10/1257
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author Seonhwa Hwang
Min-Seo Park
Anthony Junhoe Koo
Eunsoo Yoo
Seh-Hyon Song
Hye-Kyung Kim
Min-Hi Park
Jae-Seon Kang
author_facet Seonhwa Hwang
Min-Seo Park
Anthony Junhoe Koo
Eunsoo Yoo
Seh-Hyon Song
Hye-Kyung Kim
Min-Hi Park
Jae-Seon Kang
author_sort Seonhwa Hwang
collection DOAJ
description Platelets are essential blood components that maintain hemostasis, prevent excessive bleeding, and facilitate wound healing. Reduced platelet counts are implicated in various diseases, including leukemia, hepatitis, cancer, and Alzheimer’s disease. Enhancing megakaryocytic differentiation is a promising strategy to increase platelet production. Compound K (CK), a major bioactive metabolite of ginsenosides from <i>Panax ginseng</i>, has demonstrated anti-cancer and neuroprotective properties. In this study, we investigated the effects of CK on megakaryocytic differentiation and apoptosis in chronic myeloid leukemia (CML) cell lines K562 and Meg-01. CK treatment significantly upregulated the mRNA expression of key megakaryocytic differentiation markers, including CD61, CD41, and CD42a, and promoted the formation of large, multinucleated cells in K562 cells. Additionally, flow cytometry analysis revealed that CK at 5 µM induced apoptosis, a critical process in thrombocytopoiesis, in both K562 and Meg-01 cells. RT<sup>2</sup> Profiler PCR array analysis further identified a marked increase in the expression of genes associated with the activation of the NLRP3 inflammasome in CK-treated K562 and Meg-01 cells. This study is the first to demonstrate that CK promotes megakaryocytic differentiation and apoptosis through the activation of the ERK/EGR1 and NLRP3 inflammasome pathways. These findings suggest that CK may enhance platelet production, indicating its potential as a therapeutic candidate for platelet-related disorders and other associated diseases.
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spelling doaj-art-5dc79d4015ab4f1dbc1fe77378f6efe32025-08-20T02:11:12ZengMDPI AGBiomolecules2218-273X2024-10-011410125710.3390/biom14101257Compound K Promotes Megakaryocytic Differentiation by NLRP3 Inflammasome ActivationSeonhwa Hwang0Min-Seo Park1Anthony Junhoe Koo2Eunsoo Yoo3Seh-Hyon Song4Hye-Kyung Kim5Min-Hi Park6Jae-Seon Kang7College of Pharmacy, Kyungsung University, 309 Suyeong-ro, Busan 48434, Republic of KoreaCollege of Pharmacy, Kyungsung University, 309 Suyeong-ro, Busan 48434, Republic of KoreaCollege of Engineering, North Carolina A&T State University, Greensboro, NC 27411, USAChemical, Biological, and Bioengineering Department, North Carolina A&T State University, Greensboro, NC 27411, USACollege of Pharmacy, Kyungsung University, 309 Suyeong-ro, Busan 48434, Republic of KoreaCollege of Pharmacy, Kyungsung University, 309 Suyeong-ro, Busan 48434, Republic of KoreaCollege of Pharmacy, Kyungsung University, 309 Suyeong-ro, Busan 48434, Republic of KoreaCollege of Pharmacy, Kyungsung University, 309 Suyeong-ro, Busan 48434, Republic of KoreaPlatelets are essential blood components that maintain hemostasis, prevent excessive bleeding, and facilitate wound healing. Reduced platelet counts are implicated in various diseases, including leukemia, hepatitis, cancer, and Alzheimer’s disease. Enhancing megakaryocytic differentiation is a promising strategy to increase platelet production. Compound K (CK), a major bioactive metabolite of ginsenosides from <i>Panax ginseng</i>, has demonstrated anti-cancer and neuroprotective properties. In this study, we investigated the effects of CK on megakaryocytic differentiation and apoptosis in chronic myeloid leukemia (CML) cell lines K562 and Meg-01. CK treatment significantly upregulated the mRNA expression of key megakaryocytic differentiation markers, including CD61, CD41, and CD42a, and promoted the formation of large, multinucleated cells in K562 cells. Additionally, flow cytometry analysis revealed that CK at 5 µM induced apoptosis, a critical process in thrombocytopoiesis, in both K562 and Meg-01 cells. RT<sup>2</sup> Profiler PCR array analysis further identified a marked increase in the expression of genes associated with the activation of the NLRP3 inflammasome in CK-treated K562 and Meg-01 cells. This study is the first to demonstrate that CK promotes megakaryocytic differentiation and apoptosis through the activation of the ERK/EGR1 and NLRP3 inflammasome pathways. These findings suggest that CK may enhance platelet production, indicating its potential as a therapeutic candidate for platelet-related disorders and other associated diseases.https://www.mdpi.com/2218-273X/14/10/1257compound Kmegakaryocytic differentiationleukemia cellNLRP3 inflammasomeplatelets
spellingShingle Seonhwa Hwang
Min-Seo Park
Anthony Junhoe Koo
Eunsoo Yoo
Seh-Hyon Song
Hye-Kyung Kim
Min-Hi Park
Jae-Seon Kang
Compound K Promotes Megakaryocytic Differentiation by NLRP3 Inflammasome Activation
Biomolecules
compound K
megakaryocytic differentiation
leukemia cell
NLRP3 inflammasome
platelets
title Compound K Promotes Megakaryocytic Differentiation by NLRP3 Inflammasome Activation
title_full Compound K Promotes Megakaryocytic Differentiation by NLRP3 Inflammasome Activation
title_fullStr Compound K Promotes Megakaryocytic Differentiation by NLRP3 Inflammasome Activation
title_full_unstemmed Compound K Promotes Megakaryocytic Differentiation by NLRP3 Inflammasome Activation
title_short Compound K Promotes Megakaryocytic Differentiation by NLRP3 Inflammasome Activation
title_sort compound k promotes megakaryocytic differentiation by nlrp3 inflammasome activation
topic compound K
megakaryocytic differentiation
leukemia cell
NLRP3 inflammasome
platelets
url https://www.mdpi.com/2218-273X/14/10/1257
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