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(+)-Bornyl p-Coumarate Extracted from Stem of Piper betle Induced Apoptosis and Autophagy in Melanoma Cells

(+)-Bornyl p-coumarate is an active substance that is abundant in the Piper betle stem and has been shown to possess bioactivity against bacteria and a strong antioxidative effect. In the current study, we examined the actions of (+)-bornyl p-coumarate against A2058 and A375 melanoma cells. The inhi...

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Autores principales: Wu, Yu-Jen, Su, Tzu-Rong, Chang, Chi-I, Chen, Chiy-Rong, Hung, Kuo-Feng, Liu, Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279146/
https://www.ncbi.nlm.nih.gov/pubmed/32466337
http://dx.doi.org/10.3390/ijms21103737
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author Wu, Yu-Jen
Su, Tzu-Rong
Chang, Chi-I
Chen, Chiy-Rong
Hung, Kuo-Feng
Liu, Cheng
author_facet Wu, Yu-Jen
Su, Tzu-Rong
Chang, Chi-I
Chen, Chiy-Rong
Hung, Kuo-Feng
Liu, Cheng
author_sort Wu, Yu-Jen
collection PubMed
description (+)-Bornyl p-coumarate is an active substance that is abundant in the Piper betle stem and has been shown to possess bioactivity against bacteria and a strong antioxidative effect. In the current study, we examined the actions of (+)-bornyl p-coumarate against A2058 and A375 melanoma cells. The inhibition effects of (+)-bornyl p-coumarate on these cell lines were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and the underlying mechanisms were identified by immunostaining, flow cytometry and western blotting of proteins associated with apoptosis and autophagy. Our results demonstrated that (+)-bornyl p-coumarate inhibited melanoma cell proliferation and caused loss of mitochondrial membrane potential, demonstrating treatment induced apoptosis. In addition, western blotting revealed that the process is mediated by caspase-dependent pathways, release of cytochrome C, activation of pro-apoptotic proteins (Bax, Bad and caspase-3/-9) and suppression of anti-apoptotic proteins (Bcl-2, Bcl-xl and Mcl-1). Also, the upregulated expressions of p-PERK, p-eIF2α, ATF4 and CCAAT/enhancer-binding protein (C/EBP)-homologous protein (CHOP) after treatment indicated that (+)-bornyl p-coumarate caused apoptosis via endoplasmic reticulum (ER) stress. Moreover, increased expressions of beclin-1, Atg3, Atg5, p62, LC3-I and LC3-II proteins and suppression by autophagic inhibitor 3-methyladenine (3-MA), indicated that (+)-bornyl p-coumarate triggered autophagy in the melanoma cells. In conclusion, our findings demonstrated that (+)-bornyl p-coumarate suppressed human melanoma cell growth and should be further investigated with regards to its potential use as a chemotherapy drug for the treatment of human melanoma.
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spelling pubmed-72791462020-06-15 (+)-Bornyl p-Coumarate Extracted from Stem of Piper betle Induced Apoptosis and Autophagy in Melanoma Cells Wu, Yu-Jen Su, Tzu-Rong Chang, Chi-I Chen, Chiy-Rong Hung, Kuo-Feng Liu, Cheng Int J Mol Sci Article (+)-Bornyl p-coumarate is an active substance that is abundant in the Piper betle stem and has been shown to possess bioactivity against bacteria and a strong antioxidative effect. In the current study, we examined the actions of (+)-bornyl p-coumarate against A2058 and A375 melanoma cells. The inhibition effects of (+)-bornyl p-coumarate on these cell lines were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and the underlying mechanisms were identified by immunostaining, flow cytometry and western blotting of proteins associated with apoptosis and autophagy. Our results demonstrated that (+)-bornyl p-coumarate inhibited melanoma cell proliferation and caused loss of mitochondrial membrane potential, demonstrating treatment induced apoptosis. In addition, western blotting revealed that the process is mediated by caspase-dependent pathways, release of cytochrome C, activation of pro-apoptotic proteins (Bax, Bad and caspase-3/-9) and suppression of anti-apoptotic proteins (Bcl-2, Bcl-xl and Mcl-1). Also, the upregulated expressions of p-PERK, p-eIF2α, ATF4 and CCAAT/enhancer-binding protein (C/EBP)-homologous protein (CHOP) after treatment indicated that (+)-bornyl p-coumarate caused apoptosis via endoplasmic reticulum (ER) stress. Moreover, increased expressions of beclin-1, Atg3, Atg5, p62, LC3-I and LC3-II proteins and suppression by autophagic inhibitor 3-methyladenine (3-MA), indicated that (+)-bornyl p-coumarate triggered autophagy in the melanoma cells. In conclusion, our findings demonstrated that (+)-bornyl p-coumarate suppressed human melanoma cell growth and should be further investigated with regards to its potential use as a chemotherapy drug for the treatment of human melanoma. MDPI 2020-05-25 /pmc/articles/PMC7279146/ /pubmed/32466337 http://dx.doi.org/10.3390/ijms21103737 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wu, Yu-Jen
Su, Tzu-Rong
Chang, Chi-I
Chen, Chiy-Rong
Hung, Kuo-Feng
Liu, Cheng
(+)-Bornyl p-Coumarate Extracted from Stem of Piper betle Induced Apoptosis and Autophagy in Melanoma Cells
title (+)-Bornyl p-Coumarate Extracted from Stem of Piper betle Induced Apoptosis and Autophagy in Melanoma Cells
title_full (+)-Bornyl p-Coumarate Extracted from Stem of Piper betle Induced Apoptosis and Autophagy in Melanoma Cells
title_fullStr (+)-Bornyl p-Coumarate Extracted from Stem of Piper betle Induced Apoptosis and Autophagy in Melanoma Cells
title_full_unstemmed (+)-Bornyl p-Coumarate Extracted from Stem of Piper betle Induced Apoptosis and Autophagy in Melanoma Cells
title_short (+)-Bornyl p-Coumarate Extracted from Stem of Piper betle Induced Apoptosis and Autophagy in Melanoma Cells
title_sort (+)-bornyl p-coumarate extracted from stem of piper betle induced apoptosis and autophagy in melanoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279146/
https://www.ncbi.nlm.nih.gov/pubmed/32466337
http://dx.doi.org/10.3390/ijms21103737
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