Anti-cancer effect of a phytochemical compound – 7R-acetylmelodorinol – against triple-negative breast cancer cells
Triple-negative breast cancer (TNBC) is a highly aggressive subtype currently lacking effective treatment options. Consequently, novel and effective drugs or compounds are urgently needed to treat TNBC. Therefore, this study aimed to evaluate the potential of 7R-acetylmelodorinol (7R-AMDL), a phytoc...
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Format: | Article |
Language: | English |
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Elsevier
2023-10-01
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Series: | Biomedicine & Pharmacotherapy |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223010776 |
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author | Chutamas Thepmalee Nunghathai Sawasdee Phanitaporn Jenkham Chonthida Thephinlap Krissana Khoothiam Nittiya Suwannasom Ratchanaporn Chokchaisiri Aussara Panya Pa-thai Yenchitsomanus |
author_facet | Chutamas Thepmalee Nunghathai Sawasdee Phanitaporn Jenkham Chonthida Thephinlap Krissana Khoothiam Nittiya Suwannasom Ratchanaporn Chokchaisiri Aussara Panya Pa-thai Yenchitsomanus |
author_sort | Chutamas Thepmalee |
collection | DOAJ |
description | Triple-negative breast cancer (TNBC) is a highly aggressive subtype currently lacking effective treatment options. Consequently, novel and effective drugs or compounds are urgently needed to treat TNBC. Therefore, this study aimed to evaluate the potential of 7R-acetylmelodorinol (7R-AMDL), a phytochemical compound isolated from Xylopia pierrei Hance, a plant found in Thailand, as a novel therapeutic agent for TNBC. MTT and clonogenic assays showed that 7R-AMDL significantly reduced the survival of breast cancer cell lines, with a markedly potent effect on MDA-MB-231 cells. Flow cytometry showed that treating MDA-MB-231 cells with 7R-AMDL at the concentration of dose 8 µM significantly increased early and late apoptosis after 24 and 48 h compared to the control group (p < 0.0001). The highest tested 7R-AMDL dose upregulated the death receptors and their ligands, with extrinsic and intrinsic apoptosis pathways significantly activated via the caspase cascade, compared to the untreated group (p < 0.05). In addition, immunoblots showed decreased BCL2-like 1 (BCL2L1/Bcl-xL) expression (p < 0.0001). Furthermore, wound healing and Transwell assays showed that at a non-cytotoxic dose (≤4 µM), 7R-AMDL significantly inhibited the MDA-MB-231 cell migration and invasion. This reduction in cell migration was associated with decreased matrix metallopeptidase 9 (MMP-9) expression (p < 0.01) and nuclear factor kappa B (NF-κB) activation (p < 0.05). Altogether, 7R-AMDL has anti-cancer effects against TNBC and the potential to be further developed and evaluated for treating this disease. |
first_indexed | 2024-03-12T01:11:30Z |
format | Article |
id | doaj.art-19586c4d50754fa2a48c6840a0049dac |
institution | Directory Open Access Journal |
issn | 0753-3322 |
language | English |
last_indexed | 2024-03-12T01:11:30Z |
publishDate | 2023-10-01 |
publisher | Elsevier |
record_format | Article |
series | Biomedicine & Pharmacotherapy |
spelling | doaj.art-19586c4d50754fa2a48c6840a0049dac2023-09-14T04:52:31ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-10-01166115286Anti-cancer effect of a phytochemical compound – 7R-acetylmelodorinol – against triple-negative breast cancer cellsChutamas Thepmalee0Nunghathai Sawasdee1Phanitaporn Jenkham2Chonthida Thephinlap3Krissana Khoothiam4Nittiya Suwannasom5Ratchanaporn Chokchaisiri6Aussara Panya7Pa-thai Yenchitsomanus8Unit of Excellence on Research and Development of Cancer Therapy, University of Phayao, Phayao 56000, Thailand; Division of Biochemistry, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand; Corresponding author at: Division of Biochemistry, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand.Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandUnit of Excellence on Research and Development of Cancer Therapy, University of Phayao, Phayao 56000, Thailand; Division of Biochemistry, School of Medical Sciences, University of Phayao, Phayao 56000, ThailandUnit of Excellence on Research and Development of Cancer Therapy, University of Phayao, Phayao 56000, Thailand; Division of Biochemistry, School of Medical Sciences, University of Phayao, Phayao 56000, ThailandUnit of Excellence on Research and Development of Cancer Therapy, University of Phayao, Phayao 56000, Thailand; Division of Microbiology, School of Medical Sciences, University of Phayao, Phayao 56000, ThailandUnit of Excellence on Research and Development of Cancer Therapy, University of Phayao, Phayao 56000, Thailand; Division of Biochemistry, School of Medical Sciences, University of Phayao, Phayao 56000, ThailandDepartment of Chemistry, School of Science, University of Phayao, Phayao 56000, ThailandCell Engineering for Cancer Therapy Research Group, Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, ThailandSiriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandTriple-negative breast cancer (TNBC) is a highly aggressive subtype currently lacking effective treatment options. Consequently, novel and effective drugs or compounds are urgently needed to treat TNBC. Therefore, this study aimed to evaluate the potential of 7R-acetylmelodorinol (7R-AMDL), a phytochemical compound isolated from Xylopia pierrei Hance, a plant found in Thailand, as a novel therapeutic agent for TNBC. MTT and clonogenic assays showed that 7R-AMDL significantly reduced the survival of breast cancer cell lines, with a markedly potent effect on MDA-MB-231 cells. Flow cytometry showed that treating MDA-MB-231 cells with 7R-AMDL at the concentration of dose 8 µM significantly increased early and late apoptosis after 24 and 48 h compared to the control group (p < 0.0001). The highest tested 7R-AMDL dose upregulated the death receptors and their ligands, with extrinsic and intrinsic apoptosis pathways significantly activated via the caspase cascade, compared to the untreated group (p < 0.05). In addition, immunoblots showed decreased BCL2-like 1 (BCL2L1/Bcl-xL) expression (p < 0.0001). Furthermore, wound healing and Transwell assays showed that at a non-cytotoxic dose (≤4 µM), 7R-AMDL significantly inhibited the MDA-MB-231 cell migration and invasion. This reduction in cell migration was associated with decreased matrix metallopeptidase 9 (MMP-9) expression (p < 0.01) and nuclear factor kappa B (NF-κB) activation (p < 0.05). Altogether, 7R-AMDL has anti-cancer effects against TNBC and the potential to be further developed and evaluated for treating this disease.http://www.sciencedirect.com/science/article/pii/S0753332223010776Anti-cancer effectAnti-metastasis effect7R-acetylmelodorinolTriple-negative breast cancer (TNBC)MDA-MB-231 |
spellingShingle | Chutamas Thepmalee Nunghathai Sawasdee Phanitaporn Jenkham Chonthida Thephinlap Krissana Khoothiam Nittiya Suwannasom Ratchanaporn Chokchaisiri Aussara Panya Pa-thai Yenchitsomanus Anti-cancer effect of a phytochemical compound – 7R-acetylmelodorinol – against triple-negative breast cancer cells Biomedicine & Pharmacotherapy Anti-cancer effect Anti-metastasis effect 7R-acetylmelodorinol Triple-negative breast cancer (TNBC) MDA-MB-231 |
title | Anti-cancer effect of a phytochemical compound – 7R-acetylmelodorinol – against triple-negative breast cancer cells |
title_full | Anti-cancer effect of a phytochemical compound – 7R-acetylmelodorinol – against triple-negative breast cancer cells |
title_fullStr | Anti-cancer effect of a phytochemical compound – 7R-acetylmelodorinol – against triple-negative breast cancer cells |
title_full_unstemmed | Anti-cancer effect of a phytochemical compound – 7R-acetylmelodorinol – against triple-negative breast cancer cells |
title_short | Anti-cancer effect of a phytochemical compound – 7R-acetylmelodorinol – against triple-negative breast cancer cells |
title_sort | anti cancer effect of a phytochemical compound 7r acetylmelodorinol against triple negative breast cancer cells |
topic | Anti-cancer effect Anti-metastasis effect 7R-acetylmelodorinol Triple-negative breast cancer (TNBC) MDA-MB-231 |
url | http://www.sciencedirect.com/science/article/pii/S0753332223010776 |
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