Cytotoxicity of Gymnopilus purpureosquamulosus extracts on hematologic malignant cells through activation of the SAPK/JNK signaling pathway.

Treatment of hematologic malignancies is a formidable challenge for hematologists and there is an urgent need to identify safe and efficacious agents either via synthesis in the laboratory or isolation from natural products. Here, we report the cytotoxicity of extracts from mushroom Gymnopilus purpu...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Rich Milton Dulay, Benigno C Valdez, Yang Li, Seemanti Chakrabarti, Braham Dhillon, Sofronio P Kalaw, Renato G Reyes, Esperanza C Cabrera
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/91fec509212740898be1a706cbf1292f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:91fec509212740898be1a706cbf1292f
record_format	dspace
spelling	oai:doaj.org-article:91fec509212740898be1a706cbf1292f2021-12-02T20:11:11ZCytotoxicity of Gymnopilus purpureosquamulosus extracts on hematologic malignant cells through activation of the SAPK/JNK signaling pathway.1932-620310.1371/journal.pone.0252541https://doaj.org/article/91fec509212740898be1a706cbf1292f2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0252541https://doaj.org/toc/1932-6203Treatment of hematologic malignancies is a formidable challenge for hematologists and there is an urgent need to identify safe and efficacious agents either via synthesis in the laboratory or isolation from natural products. Here, we report the cytotoxicity of extracts from mushroom Gymnopilus purpureosquamulosus Høil (G. pps) and describe its molecular mechanisms. Using leukemia, lymphoma and multiple myeloma cell lines, 28-35 ppm G. pps extract inhibited cell proliferation by ~46-79%, which correlates with activation of apoptosis as indicated by increase in annexin V-positive cells (~5-8-fold), production of reactive oxygen species (~2-3-fold), cells in sub G0/G1 phase (~3-13-fold), caspase 3 enzymatic activity (~1.6-2.9-fold), DNA fragmentation, PARP1 cleavage and down-regulation of prosurvival proteins. Mitochondrial membrane potential decreased and leakage of pro-apoptotic factors to cytoplasm was observed, consistent with the activation of intrinsic apoptosis. Western blot analysis showed activation of the ASK1-MEK-SAPK/JNK and ASK1-P38 MAPK pathways possibly due to changes in the cellular redox status as suggested by decreased protein levels of peroxiredoxin, thioredoxin and thioredoxin reductase. Moreover, antioxidant N-acetylcysteine alleviated the cytotoxicity of G. pps. Pharmacological inhibition of SAPK/JNK and P38 alleviated the G. pps-mediated cytotoxicity. The extract activated apoptosis in leukemia and lymphoma patient cell samples but not in mononuclear cells from healthy donors further supporting the therapeutic values of G. pps for hematologic malignancies.Rich Milton DulayBenigno C ValdezYang LiSeemanti ChakrabartiBraham DhillonSofronio P KalawRenato G ReyesEsperanza C CabreraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0252541 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rich Milton Dulay Benigno C Valdez Yang Li Seemanti Chakrabarti Braham Dhillon Sofronio P Kalaw Renato G Reyes Esperanza C Cabrera Cytotoxicity of Gymnopilus purpureosquamulosus extracts on hematologic malignant cells through activation of the SAPK/JNK signaling pathway.
description	Treatment of hematologic malignancies is a formidable challenge for hematologists and there is an urgent need to identify safe and efficacious agents either via synthesis in the laboratory or isolation from natural products. Here, we report the cytotoxicity of extracts from mushroom Gymnopilus purpureosquamulosus Høil (G. pps) and describe its molecular mechanisms. Using leukemia, lymphoma and multiple myeloma cell lines, 28-35 ppm G. pps extract inhibited cell proliferation by ~46-79%, which correlates with activation of apoptosis as indicated by increase in annexin V-positive cells (~5-8-fold), production of reactive oxygen species (~2-3-fold), cells in sub G0/G1 phase (~3-13-fold), caspase 3 enzymatic activity (~1.6-2.9-fold), DNA fragmentation, PARP1 cleavage and down-regulation of prosurvival proteins. Mitochondrial membrane potential decreased and leakage of pro-apoptotic factors to cytoplasm was observed, consistent with the activation of intrinsic apoptosis. Western blot analysis showed activation of the ASK1-MEK-SAPK/JNK and ASK1-P38 MAPK pathways possibly due to changes in the cellular redox status as suggested by decreased protein levels of peroxiredoxin, thioredoxin and thioredoxin reductase. Moreover, antioxidant N-acetylcysteine alleviated the cytotoxicity of G. pps. Pharmacological inhibition of SAPK/JNK and P38 alleviated the G. pps-mediated cytotoxicity. The extract activated apoptosis in leukemia and lymphoma patient cell samples but not in mononuclear cells from healthy donors further supporting the therapeutic values of G. pps for hematologic malignancies.
format	article
author	Rich Milton Dulay Benigno C Valdez Yang Li Seemanti Chakrabarti Braham Dhillon Sofronio P Kalaw Renato G Reyes Esperanza C Cabrera
author_facet	Rich Milton Dulay Benigno C Valdez Yang Li Seemanti Chakrabarti Braham Dhillon Sofronio P Kalaw Renato G Reyes Esperanza C Cabrera
author_sort	Rich Milton Dulay
title	Cytotoxicity of Gymnopilus purpureosquamulosus extracts on hematologic malignant cells through activation of the SAPK/JNK signaling pathway.
title_short	Cytotoxicity of Gymnopilus purpureosquamulosus extracts on hematologic malignant cells through activation of the SAPK/JNK signaling pathway.
title_full	Cytotoxicity of Gymnopilus purpureosquamulosus extracts on hematologic malignant cells through activation of the SAPK/JNK signaling pathway.
title_fullStr	Cytotoxicity of Gymnopilus purpureosquamulosus extracts on hematologic malignant cells through activation of the SAPK/JNK signaling pathway.
title_full_unstemmed	Cytotoxicity of Gymnopilus purpureosquamulosus extracts on hematologic malignant cells through activation of the SAPK/JNK signaling pathway.
title_sort	cytotoxicity of gymnopilus purpureosquamulosus extracts on hematologic malignant cells through activation of the sapk/jnk signaling pathway.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/91fec509212740898be1a706cbf1292f
work_keys_str_mv	AT richmiltondulay cytotoxicityofgymnopiluspurpureosquamulosusextractsonhematologicmalignantcellsthroughactivationofthesapkjnksignalingpathway AT benignocvaldez cytotoxicityofgymnopiluspurpureosquamulosusextractsonhematologicmalignantcellsthroughactivationofthesapkjnksignalingpathway AT yangli cytotoxicityofgymnopiluspurpureosquamulosusextractsonhematologicmalignantcellsthroughactivationofthesapkjnksignalingpathway AT seemantichakrabarti cytotoxicityofgymnopiluspurpureosquamulosusextractsonhematologicmalignantcellsthroughactivationofthesapkjnksignalingpathway AT brahamdhillon cytotoxicityofgymnopiluspurpureosquamulosusextractsonhematologicmalignantcellsthroughactivationofthesapkjnksignalingpathway AT sofroniopkalaw cytotoxicityofgymnopiluspurpureosquamulosusextractsonhematologicmalignantcellsthroughactivationofthesapkjnksignalingpathway AT renatogreyes cytotoxicityofgymnopiluspurpureosquamulosusextractsonhematologicmalignantcellsthroughactivationofthesapkjnksignalingpathway AT esperanzaccabrera cytotoxicityofgymnopiluspurpureosquamulosusextractsonhematologicmalignantcellsthroughactivationofthesapkjnksignalingpathway
_version_	1718374959982575616

Cytotoxicity of Gymnopilus purpureosquamulosus extracts on hematologic malignant cells through activation of the SAPK/JNK signaling pathway.

Ejemplares similares