Effects of barakol from Cassia siamea on neuroblastoma SH-SY5Y cell line: A potential combined therapy with doxorubicin

Management of neuroblastoma is challenging because of poor response to drugs, chemotherapy resistance, high relapse, and treatment failures. Doxorubicin is a potent anticancer drug commonly used for neuroblastoma treatment. However, doxorubicin induces considerable toxicities, particularly those cau...

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Main Authors: Orapin Wongsawatkul, Paiwan Buachan, Yamaratee Jaisin, Panaree Busarakumtragul, Sunan Chainakul, Ramida Watanapokasin, Veda Prachayasittikul, Supaluk Prachayasittikul, Somsak Ruchirawat, Virapong Prachayasittikul
Format: Article
Language:English
Published: Elsevier 2024-02-01
Series:Heliyon
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405844024007254
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author Orapin Wongsawatkul
Paiwan Buachan
Yamaratee Jaisin
Panaree Busarakumtragul
Sunan Chainakul
Ramida Watanapokasin
Veda Prachayasittikul
Supaluk Prachayasittikul
Somsak Ruchirawat
Virapong Prachayasittikul
author_facet Orapin Wongsawatkul
Paiwan Buachan
Yamaratee Jaisin
Panaree Busarakumtragul
Sunan Chainakul
Ramida Watanapokasin
Veda Prachayasittikul
Supaluk Prachayasittikul
Somsak Ruchirawat
Virapong Prachayasittikul
author_sort Orapin Wongsawatkul
collection DOAJ
description Management of neuroblastoma is challenging because of poor response to drugs, chemotherapy resistance, high relapse, and treatment failures. Doxorubicin is a potent anticancer drug commonly used for neuroblastoma treatment. However, doxorubicin induces considerable toxicities, particularly those caused by oxidative-related damage. To minimize drug-induced adverse effects, the combined use of anticancer drugs with natural-derived compounds possessing antioxidant properties has become an interesting treatment strategy. Barakol is a major compound found in Cassia siamea, an edible plant with antioxidant and anticancer properties. Therefore, barakol could potentially be used in combination with doxorubicin to synergize the anticancer effect, while minimizing the oxidative-related toxicities. Herein, the potential of barakol (0.0043–43.0 μM) to synergize the anticancer effect of low-dose doxorubicin (0.5 and 1.0 μM) was investigated. Results indicated that barakol could enhance the cytotoxic effect of low-dose doxorubicin by affecting the cell viability of the treated cells. Furthermore, the co-treatment with barakol and low-dose doxorubicin decreased the levels of intracellular ROS when compared with the control. Moreover, the antimetastatic effect of the barakol itself was studied through its ability to inhibit metalloproteinase-3 (MMP-3) activity and prevent cell migration. Results revealed that the barakol inhibited MMP-3 activity and prevented cell migration in time- and dose-dependent manners. Additionally, barakol was a non-cytotoxic agent against the normal tested cell line (MRC-5), which suggested its selectivity and safety. Taken together, barakol could be a promising compound to be further developed for combination treatment with low-dose doxorubicin to improve therapeutic effectiveness but decrease drug-induced toxicities. The inhibitory effects of barakol on MMP-3 activity and cancer cell migration also supported its potential to be developed as an antimetastatic agent.
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spelling doaj.art-f3770566f24348f49aca9d041c5924e22024-02-17T06:38:27ZengElsevierHeliyon2405-84402024-02-01103e24694Effects of barakol from Cassia siamea on neuroblastoma SH-SY5Y cell line: A potential combined therapy with doxorubicinOrapin Wongsawatkul0Paiwan Buachan1Yamaratee Jaisin2Panaree Busarakumtragul3Sunan Chainakul4Ramida Watanapokasin5Veda Prachayasittikul6Supaluk Prachayasittikul7Somsak Ruchirawat8Virapong Prachayasittikul9Department of Pharmacology, Faculty of Medicine, Srinakharinwirot University, Bangkok, 10110, Thailand; Corresponding author.Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, 10700, ThailandDepartment of Pharmacology, Faculty of Medicine, Srinakharinwirot University, Bangkok, 10110, ThailandDepartment of Physiology, Faculty of Medicine, Srinakharinwirot University, Bangkok, 10110, ThailandDepartment of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok, 10110, ThailandDepartment of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Bangkok, 10110, ThailandCenter for Research Innovation and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, 10700, Thailand; Corresponding author.Center for Research Innovation and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, 10700, ThailandLaboratory of Medicinal Chemistry, Chulabhorn Research Institute, Bangkok, 10210, Thailand; Program in Chemical Sciences, Chulabhorn Graduate Institute, Bangkok, 10210, Thailand; Center of Excellence on Environmental Health and Toxicology (EHT), Commission on Higher Education, Ministry of Education, Bangkok, 10400, ThailandDepartment of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, 10700, ThailandManagement of neuroblastoma is challenging because of poor response to drugs, chemotherapy resistance, high relapse, and treatment failures. Doxorubicin is a potent anticancer drug commonly used for neuroblastoma treatment. However, doxorubicin induces considerable toxicities, particularly those caused by oxidative-related damage. To minimize drug-induced adverse effects, the combined use of anticancer drugs with natural-derived compounds possessing antioxidant properties has become an interesting treatment strategy. Barakol is a major compound found in Cassia siamea, an edible plant with antioxidant and anticancer properties. Therefore, barakol could potentially be used in combination with doxorubicin to synergize the anticancer effect, while minimizing the oxidative-related toxicities. Herein, the potential of barakol (0.0043–43.0 μM) to synergize the anticancer effect of low-dose doxorubicin (0.5 and 1.0 μM) was investigated. Results indicated that barakol could enhance the cytotoxic effect of low-dose doxorubicin by affecting the cell viability of the treated cells. Furthermore, the co-treatment with barakol and low-dose doxorubicin decreased the levels of intracellular ROS when compared with the control. Moreover, the antimetastatic effect of the barakol itself was studied through its ability to inhibit metalloproteinase-3 (MMP-3) activity and prevent cell migration. Results revealed that the barakol inhibited MMP-3 activity and prevented cell migration in time- and dose-dependent manners. Additionally, barakol was a non-cytotoxic agent against the normal tested cell line (MRC-5), which suggested its selectivity and safety. Taken together, barakol could be a promising compound to be further developed for combination treatment with low-dose doxorubicin to improve therapeutic effectiveness but decrease drug-induced toxicities. The inhibitory effects of barakol on MMP-3 activity and cancer cell migration also supported its potential to be developed as an antimetastatic agent.http://www.sciencedirect.com/science/article/pii/S2405844024007254BarakolSH-SY5Y cellAnticancerMetalloproteinase-3 inhibitorReactive oxygen speciesCombination therapy
spellingShingle Orapin Wongsawatkul
Paiwan Buachan
Yamaratee Jaisin
Panaree Busarakumtragul
Sunan Chainakul
Ramida Watanapokasin
Veda Prachayasittikul
Supaluk Prachayasittikul
Somsak Ruchirawat
Virapong Prachayasittikul
Effects of barakol from Cassia siamea on neuroblastoma SH-SY5Y cell line: A potential combined therapy with doxorubicin
Heliyon
Barakol
SH-SY5Y cell
Anticancer
Metalloproteinase-3 inhibitor
Reactive oxygen species
Combination therapy
title Effects of barakol from Cassia siamea on neuroblastoma SH-SY5Y cell line: A potential combined therapy with doxorubicin
title_full Effects of barakol from Cassia siamea on neuroblastoma SH-SY5Y cell line: A potential combined therapy with doxorubicin
title_fullStr Effects of barakol from Cassia siamea on neuroblastoma SH-SY5Y cell line: A potential combined therapy with doxorubicin
title_full_unstemmed Effects of barakol from Cassia siamea on neuroblastoma SH-SY5Y cell line: A potential combined therapy with doxorubicin
title_short Effects of barakol from Cassia siamea on neuroblastoma SH-SY5Y cell line: A potential combined therapy with doxorubicin
title_sort effects of barakol from cassia siamea on neuroblastoma sh sy5y cell line a potential combined therapy with doxorubicin
topic Barakol
SH-SY5Y cell
Anticancer
Metalloproteinase-3 inhibitor
Reactive oxygen species
Combination therapy
url http://www.sciencedirect.com/science/article/pii/S2405844024007254
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