Cytotoxic properties, glycolytic effects and high-resolution respirometry mitochondrial activities of Eriocephalus racemosus against MDA-MB 231 triple-negative breast cancer
Abstract Introduction Triple-negative breast cancer (TNBC) represents a significant global health crisis due to its resistance to conventional therapies and lack of specific molecular targets. This study explored the potential of Eriocephalus racemosus (E. racemosus) as an alternative treatment for...
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BMC
2024-09-01
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| Series: | BMC Complementary Medicine and Therapies |
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| Online Access: | https://doi.org/10.1186/s12906-024-04615-x |
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| author | Francis Adu-Amankwaah Candice Februarie Kudakwashe Nyambo Gerald Maarman Ndivhuwo Tshililo Lawrence Mabasa Vuyo Mavumengwana Lucinda Baatjies |
| author_facet | Francis Adu-Amankwaah Candice Februarie Kudakwashe Nyambo Gerald Maarman Ndivhuwo Tshililo Lawrence Mabasa Vuyo Mavumengwana Lucinda Baatjies |
| author_sort | Francis Adu-Amankwaah |
| collection | DOAJ |
| description | Abstract Introduction Triple-negative breast cancer (TNBC) represents a significant global health crisis due to its resistance to conventional therapies and lack of specific molecular targets. This study explored the potential of Eriocephalus racemosus (E. racemosus) as an alternative treatment for TNBC. The cytotoxic properties and high-resolution respirometry mitochondrial activities of E. racemosus against the MDA-MB 231 TNBC cell line were evaluated. Methods Hexane solvent and bioactive fraction extractions of E. racemosus were performed, while mass spectrometry-based metabolite profiling was used to identify the phytochemical constituents of the extracts. The extracts were further tested against MDA-MB 231 TNBC cells to determine their cytotoxicity. The mode of cell death was determined using flow cytometry. The activities of caspases 3, 8, and 9 were assessed using a multiplex activity assay kit. Glycolytic activity and High-resolution respirometry measurements of mitochondrial function in the MDA-MB 231 cell line were conducted using the Seahorse XFp and Oroboros O2K. Results Metabolite profiling of E. racemosus plant crude extracts identified the presence of coumarins, flavonoids, sesquiterpenoids, triterpenoids, and unknown compounds. The extracts demonstrated promising cytotoxic activities, with a half maximal inhibitory concentration (IC50) of 12.84 µg/mL for the crude hexane extract and 15.49 µg/mL for the bioactive fraction. Further, the crude hexane and bioactive fraction extracts induced apoptosis in the MDA-MB-231 TNBC cells, like the reference drug cisplatin (17.44%, 17.26% and 20.25%, respectively) compared to untreated cells. Caspase 3 activities confirmed the induction of apoptosis in both cisplatin and the plant crude extracts, while caspase 8 and 9 activities confirmed the activation of both the intrinsic and extrinsic apoptosis pathways. Increased levels of glycolytic activity were observed in the hexane crude extract. High-resolution respiratory measurements showed elevated mitochondrial activities in all mitochondrial states except for complex-IV activity. Conclusion These findings support further exploration of E. racemosus as a potential therapeutic agent for TNBC, offering a promising avenue for the development of targeted treatments with minimal adverse effects. |
| format | Article |
| id | doaj-art-dd29b233fd2945f1ad855ac776a8ec52 |
| institution | DOAJ |
| issn | 2662-7671 |
| language | English |
| publishDate | 2024-09-01 |
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| series | BMC Complementary Medicine and Therapies |
| spelling | doaj-art-dd29b233fd2945f1ad855ac776a8ec522025-08-20T02:59:31ZengBMCBMC Complementary Medicine and Therapies2662-76712024-09-0124112110.1186/s12906-024-04615-xCytotoxic properties, glycolytic effects and high-resolution respirometry mitochondrial activities of Eriocephalus racemosus against MDA-MB 231 triple-negative breast cancerFrancis Adu-Amankwaah0Candice Februarie1Kudakwashe Nyambo2Gerald Maarman3Ndivhuwo Tshililo4Lawrence Mabasa5Vuyo Mavumengwana6Lucinda Baatjies7South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch UniversityDivision of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine & Health Science, CARMA: Centre for Cardio-Metabolic Research in Africa, Stellenbosch UniversitySouth African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch UniversityDivision of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine & Health Science, CARMA: Centre for Cardio-Metabolic Research in Africa, Stellenbosch UniversitySouth African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch UniversityBiomedical Research and Innovation Platform (BRIP), Medical Research CouncilSouth African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch UniversitySouth African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch UniversityAbstract Introduction Triple-negative breast cancer (TNBC) represents a significant global health crisis due to its resistance to conventional therapies and lack of specific molecular targets. This study explored the potential of Eriocephalus racemosus (E. racemosus) as an alternative treatment for TNBC. The cytotoxic properties and high-resolution respirometry mitochondrial activities of E. racemosus against the MDA-MB 231 TNBC cell line were evaluated. Methods Hexane solvent and bioactive fraction extractions of E. racemosus were performed, while mass spectrometry-based metabolite profiling was used to identify the phytochemical constituents of the extracts. The extracts were further tested against MDA-MB 231 TNBC cells to determine their cytotoxicity. The mode of cell death was determined using flow cytometry. The activities of caspases 3, 8, and 9 were assessed using a multiplex activity assay kit. Glycolytic activity and High-resolution respirometry measurements of mitochondrial function in the MDA-MB 231 cell line were conducted using the Seahorse XFp and Oroboros O2K. Results Metabolite profiling of E. racemosus plant crude extracts identified the presence of coumarins, flavonoids, sesquiterpenoids, triterpenoids, and unknown compounds. The extracts demonstrated promising cytotoxic activities, with a half maximal inhibitory concentration (IC50) of 12.84 µg/mL for the crude hexane extract and 15.49 µg/mL for the bioactive fraction. Further, the crude hexane and bioactive fraction extracts induced apoptosis in the MDA-MB-231 TNBC cells, like the reference drug cisplatin (17.44%, 17.26% and 20.25%, respectively) compared to untreated cells. Caspase 3 activities confirmed the induction of apoptosis in both cisplatin and the plant crude extracts, while caspase 8 and 9 activities confirmed the activation of both the intrinsic and extrinsic apoptosis pathways. Increased levels of glycolytic activity were observed in the hexane crude extract. High-resolution respiratory measurements showed elevated mitochondrial activities in all mitochondrial states except for complex-IV activity. Conclusion These findings support further exploration of E. racemosus as a potential therapeutic agent for TNBC, offering a promising avenue for the development of targeted treatments with minimal adverse effects.https://doi.org/10.1186/s12906-024-04615-xTriple-negative breast cancerCell deathEriocephalus racemosusFlow cytometryGlycolysisMitochondrial activities |
| spellingShingle | Francis Adu-Amankwaah Candice Februarie Kudakwashe Nyambo Gerald Maarman Ndivhuwo Tshililo Lawrence Mabasa Vuyo Mavumengwana Lucinda Baatjies Cytotoxic properties, glycolytic effects and high-resolution respirometry mitochondrial activities of Eriocephalus racemosus against MDA-MB 231 triple-negative breast cancer BMC Complementary Medicine and Therapies Triple-negative breast cancer Cell death Eriocephalus racemosus Flow cytometry Glycolysis Mitochondrial activities |
| title | Cytotoxic properties, glycolytic effects and high-resolution respirometry mitochondrial activities of Eriocephalus racemosus against MDA-MB 231 triple-negative breast cancer |
| title_full | Cytotoxic properties, glycolytic effects and high-resolution respirometry mitochondrial activities of Eriocephalus racemosus against MDA-MB 231 triple-negative breast cancer |
| title_fullStr | Cytotoxic properties, glycolytic effects and high-resolution respirometry mitochondrial activities of Eriocephalus racemosus against MDA-MB 231 triple-negative breast cancer |
| title_full_unstemmed | Cytotoxic properties, glycolytic effects and high-resolution respirometry mitochondrial activities of Eriocephalus racemosus against MDA-MB 231 triple-negative breast cancer |
| title_short | Cytotoxic properties, glycolytic effects and high-resolution respirometry mitochondrial activities of Eriocephalus racemosus against MDA-MB 231 triple-negative breast cancer |
| title_sort | cytotoxic properties glycolytic effects and high resolution respirometry mitochondrial activities of eriocephalus racemosus against mda mb 231 triple negative breast cancer |
| topic | Triple-negative breast cancer Cell death Eriocephalus racemosus Flow cytometry Glycolysis Mitochondrial activities |
| url | https://doi.org/10.1186/s12906-024-04615-x |
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