Green synthesized apigenin conjugated gold nanoparticles inhibit cholangiocarcinoma cell activity and endothelial cell angiogenesis in vitro

Cholangiocarcinoma (CCA) is a rare malignancy of the biliary tract with extremely poor clinical outcomes due to a lack of effective therapies to improve disease management. The emerging green synthesis of gold nanoparticles (AuNPs) has extensively provided their use in biomedical applications. In th...

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Main Authors: Nipaporn Ngernyuang, Molin Wongwattanakul, Wannit Charusirisawad, Rong Shao, Temduang Limpaiboon
Format: Article
Language:English
Published: Elsevier 2022-12-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844022033163
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author Nipaporn Ngernyuang
Molin Wongwattanakul
Wannit Charusirisawad
Rong Shao
Temduang Limpaiboon
author_facet Nipaporn Ngernyuang
Molin Wongwattanakul
Wannit Charusirisawad
Rong Shao
Temduang Limpaiboon
author_sort Nipaporn Ngernyuang
collection DOAJ
description Cholangiocarcinoma (CCA) is a rare malignancy of the biliary tract with extremely poor clinical outcomes due to a lack of effective therapies to improve disease management. The emerging green synthesis of gold nanoparticles (AuNPs) has extensively provided their use in biomedical applications. In this study, we developed AuNPs via reducing gold salts with apigenin (4′,5,7-trihydroxyflavone). The synthesized apigenin-conjugated AuNPs (api-AuNPs) were physicochemically characterized by various techniques before evaluation their biological and functional inhibition in a CCA cell line, KKU-M055. The mean size of api-AuNPs was 90.34 ± 22.82 nm with zeta potential of -36 ± 0.55. The half-maximal inhibitory concentration (IC50, 0.8 mg/mL) of api-AuNPs on cell proliferation of KKU-M055 was 1.9-fold less than that of an immortalized human cholangiocyte cell line, MMNK1 (IC50, 1.5 mg/mL). Moreover, api-AuNPs induced cell apoptosis via the up-regulation of Bax, Bid, and Caspase 3, and down-regulation of Bcl2, leading to elevated caspase 3/7, 8, 9 activities and reactive oxygen species (ROS) production. The api-AuNPs significantly inhibited the migration of KKU-M055 cells and suppressed the proliferation, migration, and in vitro tube formation of vascular endothelial cells. Collectively, our findings indicate the dual abilities of api-AuNPs that potentially inhibit cancer cell growth and motility as well as endothelial cell-mediated angiogenesis, which may offer a novel therapeutic avenue to treat CCA patients effectively.
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spelling doaj.art-4822b53e180c4323a94df673ecf57eca2023-01-05T08:38:01ZengElsevierHeliyon2405-84402022-12-01812e12028Green synthesized apigenin conjugated gold nanoparticles inhibit cholangiocarcinoma cell activity and endothelial cell angiogenesis in vitroNipaporn Ngernyuang0Molin Wongwattanakul1Wannit Charusirisawad2Rong Shao3Temduang Limpaiboon4Chulabhorn International College of Medicine, Thammasat University, Pathum Thani 12120, ThailandCentre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Science, Khon Kaen University, Khon Kaen 40002, ThailandChulabhorn International College of Medicine, Thammasat University, Pathum Thani 12120, ThailandDevelopment of Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaCentre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Science, Khon Kaen University, Khon Kaen 40002, Thailand; Corresponding author.Cholangiocarcinoma (CCA) is a rare malignancy of the biliary tract with extremely poor clinical outcomes due to a lack of effective therapies to improve disease management. The emerging green synthesis of gold nanoparticles (AuNPs) has extensively provided their use in biomedical applications. In this study, we developed AuNPs via reducing gold salts with apigenin (4′,5,7-trihydroxyflavone). The synthesized apigenin-conjugated AuNPs (api-AuNPs) were physicochemically characterized by various techniques before evaluation their biological and functional inhibition in a CCA cell line, KKU-M055. The mean size of api-AuNPs was 90.34 ± 22.82 nm with zeta potential of -36 ± 0.55. The half-maximal inhibitory concentration (IC50, 0.8 mg/mL) of api-AuNPs on cell proliferation of KKU-M055 was 1.9-fold less than that of an immortalized human cholangiocyte cell line, MMNK1 (IC50, 1.5 mg/mL). Moreover, api-AuNPs induced cell apoptosis via the up-regulation of Bax, Bid, and Caspase 3, and down-regulation of Bcl2, leading to elevated caspase 3/7, 8, 9 activities and reactive oxygen species (ROS) production. The api-AuNPs significantly inhibited the migration of KKU-M055 cells and suppressed the proliferation, migration, and in vitro tube formation of vascular endothelial cells. Collectively, our findings indicate the dual abilities of api-AuNPs that potentially inhibit cancer cell growth and motility as well as endothelial cell-mediated angiogenesis, which may offer a novel therapeutic avenue to treat CCA patients effectively.http://www.sciencedirect.com/science/article/pii/S2405844022033163ApigeninGold nanoparticlesGreen synthesisCholangiocarcinomaApoptosis
spellingShingle Nipaporn Ngernyuang
Molin Wongwattanakul
Wannit Charusirisawad
Rong Shao
Temduang Limpaiboon
Green synthesized apigenin conjugated gold nanoparticles inhibit cholangiocarcinoma cell activity and endothelial cell angiogenesis in vitro
Heliyon
Apigenin
Gold nanoparticles
Green synthesis
Cholangiocarcinoma
Apoptosis
title Green synthesized apigenin conjugated gold nanoparticles inhibit cholangiocarcinoma cell activity and endothelial cell angiogenesis in vitro
title_full Green synthesized apigenin conjugated gold nanoparticles inhibit cholangiocarcinoma cell activity and endothelial cell angiogenesis in vitro
title_fullStr Green synthesized apigenin conjugated gold nanoparticles inhibit cholangiocarcinoma cell activity and endothelial cell angiogenesis in vitro
title_full_unstemmed Green synthesized apigenin conjugated gold nanoparticles inhibit cholangiocarcinoma cell activity and endothelial cell angiogenesis in vitro
title_short Green synthesized apigenin conjugated gold nanoparticles inhibit cholangiocarcinoma cell activity and endothelial cell angiogenesis in vitro
title_sort green synthesized apigenin conjugated gold nanoparticles inhibit cholangiocarcinoma cell activity and endothelial cell angiogenesis in vitro
topic Apigenin
Gold nanoparticles
Green synthesis
Cholangiocarcinoma
Apoptosis
url http://www.sciencedirect.com/science/article/pii/S2405844022033163
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AT molinwongwattanakul greensynthesizedapigeninconjugatedgoldnanoparticlesinhibitcholangiocarcinomacellactivityandendothelialcellangiogenesisinvitro
AT wannitcharusirisawad greensynthesizedapigeninconjugatedgoldnanoparticlesinhibitcholangiocarcinomacellactivityandendothelialcellangiogenesisinvitro
AT rongshao greensynthesizedapigeninconjugatedgoldnanoparticlesinhibitcholangiocarcinomacellactivityandendothelialcellangiogenesisinvitro
AT temduanglimpaiboon greensynthesizedapigeninconjugatedgoldnanoparticlesinhibitcholangiocarcinomacellactivityandendothelialcellangiogenesisinvitro