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...

Full description

Bibliographic Details
Main Authors: Chutamas Thepmalee, Nunghathai Sawasdee, Phanitaporn Jenkham, Chonthida Thephinlap, Krissana Khoothiam, Nittiya Suwannasom, Ratchanaporn Chokchaisiri, Aussara Panya, Pa-thai Yenchitsomanus
Format: Article
Language:English
Published: Elsevier 2023-10-01
Series:Biomedicine & Pharmacotherapy
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0753332223010776
_version_ 1797686834558402560
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
work_keys_str_mv AT chutamasthepmalee anticancereffectofaphytochemicalcompound7racetylmelodorinolagainsttriplenegativebreastcancercells
AT nunghathaisawasdee anticancereffectofaphytochemicalcompound7racetylmelodorinolagainsttriplenegativebreastcancercells
AT phanitapornjenkham anticancereffectofaphytochemicalcompound7racetylmelodorinolagainsttriplenegativebreastcancercells
AT chonthidathephinlap anticancereffectofaphytochemicalcompound7racetylmelodorinolagainsttriplenegativebreastcancercells
AT krissanakhoothiam anticancereffectofaphytochemicalcompound7racetylmelodorinolagainsttriplenegativebreastcancercells
AT nittiyasuwannasom anticancereffectofaphytochemicalcompound7racetylmelodorinolagainsttriplenegativebreastcancercells
AT ratchanapornchokchaisiri anticancereffectofaphytochemicalcompound7racetylmelodorinolagainsttriplenegativebreastcancercells
AT aussarapanya anticancereffectofaphytochemicalcompound7racetylmelodorinolagainsttriplenegativebreastcancercells
AT pathaiyenchitsomanus anticancereffectofaphytochemicalcompound7racetylmelodorinolagainsttriplenegativebreastcancercells