The combination of Elephantopus scaber and Phaleria macrocarpa leaves extract promotes anticancer activity via downregulation of ER-α, Nrf2 and PI3K/AKT/mTOR pathway
Background: Elephantopus scaber and Phaleria macrocarpa have recently been interested as novel anticancer agents. However, there was no scientific evaluation of the anticancer effect of both plant combinations. Objective: This study investigated the potential anticancer effects of combined E. scaber...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | Journal of Ayurveda and Integrative Medicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0975947622001334 |
| _version_ | 1797978818333376512 |
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| author | Yuyun Ika Christina Muhaimin Rifa’i Nashi Widodo Muhammad Sasmito Djati |
| author_facet | Yuyun Ika Christina Muhaimin Rifa’i Nashi Widodo Muhammad Sasmito Djati |
| author_sort | Yuyun Ika Christina |
| collection | DOAJ |
| description | Background: Elephantopus scaber and Phaleria macrocarpa have recently been interested as novel anticancer agents. However, there was no scientific evaluation of the anticancer effect of both plant combinations. Objective: This study investigated the potential anticancer effects of combined E. scaber and P. macrocarpa leaves extract on human breast cancer cells lines. Materials and methods: T47D cells were treated with the combination of E. scaber and each part of P. macrocarpa (leaves/EL, mesocarp/EM, seed/ES and pericarp/EP). T47D cells were then exposed to three ratios (1:1, 2:1, and 1:2) of the best combination for 24, 48, and 72 h. The cell viability of T47D and TIG-1 cells was assessed using WST-1 assay. The apoptotic hallmarks were determined using FITC Annexin V-PI staining and DNA fragmentation assay. The cell proliferation and cell cycle profiles were analyzed using CFSE (carboxyfluorescein succinimidyl ester) and Propidium iodide-flowcytometry assays. The relative number of p-ERα, p-Nrf2, p-PI3K, p-AKT, and p-mTOR were assessed using flow cytometry. The molecular docking analysis was also performed to confirm the mechanism of the extract in silico. Results: The combination of E. scaber and P. macrocarpa leaves (EL) possessed strong cytotoxic activity (p < 0.05) than other combination groups and cisplatin. EL showed selective killing only to T47D cells. EL at a ratio of 2:1 potentially suppressed the cell viability and cell division, induced apoptosis, and arrested the cell cycle of T47D cells by triple inhibiting the p-Nrf2, p-ERα, and p-PI3K/AKT/mTOR signaling pathway. Molecular docking analysis confirmed that the possible mechanism of EL to reduce T47D cell growth was by inhibiting ERα and Nrf2-complex, resulting in the reduction in the crosstalk effect of Nrf2, ERα and PI3K/AKT/mTOR pathways. Conclusion: The combination of leaf extracts from E. scaber and P. macrocarpa caused cell death in breast cancer cells T47D and not in normal cells TIG-1; hence has the potential to show anticancer efficacy in preclinical and clinical trials. |
| first_indexed | 2024-04-11T05:28:51Z |
| format | Article |
| id | doaj.art-03e841b8e671488ab1443779f1b2cc9e |
| institution | Directory Open Access Journal |
| issn | 0975-9476 |
| language | English |
| last_indexed | 2024-04-11T05:28:51Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Ayurveda and Integrative Medicine |
| spelling | doaj.art-03e841b8e671488ab1443779f1b2cc9e2022-12-23T04:37:38ZengElsevierJournal of Ayurveda and Integrative Medicine0975-94762022-10-01134100674The combination of Elephantopus scaber and Phaleria macrocarpa leaves extract promotes anticancer activity via downregulation of ER-α, Nrf2 and PI3K/AKT/mTOR pathwayYuyun Ika Christina0Muhaimin Rifa’i1Nashi Widodo2Muhammad Sasmito Djati3Doctoral Program, Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang 65145, East Java, IndonesiaDepartment of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang 65145, East Java, IndonesiaDepartment of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang 65145, East Java, IndonesiaDepartment of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang 65145, East Java, Indonesia; Corresponding author.Background: Elephantopus scaber and Phaleria macrocarpa have recently been interested as novel anticancer agents. However, there was no scientific evaluation of the anticancer effect of both plant combinations. Objective: This study investigated the potential anticancer effects of combined E. scaber and P. macrocarpa leaves extract on human breast cancer cells lines. Materials and methods: T47D cells were treated with the combination of E. scaber and each part of P. macrocarpa (leaves/EL, mesocarp/EM, seed/ES and pericarp/EP). T47D cells were then exposed to three ratios (1:1, 2:1, and 1:2) of the best combination for 24, 48, and 72 h. The cell viability of T47D and TIG-1 cells was assessed using WST-1 assay. The apoptotic hallmarks were determined using FITC Annexin V-PI staining and DNA fragmentation assay. The cell proliferation and cell cycle profiles were analyzed using CFSE (carboxyfluorescein succinimidyl ester) and Propidium iodide-flowcytometry assays. The relative number of p-ERα, p-Nrf2, p-PI3K, p-AKT, and p-mTOR were assessed using flow cytometry. The molecular docking analysis was also performed to confirm the mechanism of the extract in silico. Results: The combination of E. scaber and P. macrocarpa leaves (EL) possessed strong cytotoxic activity (p < 0.05) than other combination groups and cisplatin. EL showed selective killing only to T47D cells. EL at a ratio of 2:1 potentially suppressed the cell viability and cell division, induced apoptosis, and arrested the cell cycle of T47D cells by triple inhibiting the p-Nrf2, p-ERα, and p-PI3K/AKT/mTOR signaling pathway. Molecular docking analysis confirmed that the possible mechanism of EL to reduce T47D cell growth was by inhibiting ERα and Nrf2-complex, resulting in the reduction in the crosstalk effect of Nrf2, ERα and PI3K/AKT/mTOR pathways. Conclusion: The combination of leaf extracts from E. scaber and P. macrocarpa caused cell death in breast cancer cells T47D and not in normal cells TIG-1; hence has the potential to show anticancer efficacy in preclinical and clinical trials.http://www.sciencedirect.com/science/article/pii/S0975947622001334AnticancerApoptosisCombination extractE. scaber leavesP. macrocarpa leavesPI3K/AKT/mTOR |
| spellingShingle | Yuyun Ika Christina Muhaimin Rifa’i Nashi Widodo Muhammad Sasmito Djati The combination of Elephantopus scaber and Phaleria macrocarpa leaves extract promotes anticancer activity via downregulation of ER-α, Nrf2 and PI3K/AKT/mTOR pathway Journal of Ayurveda and Integrative Medicine Anticancer Apoptosis Combination extract E. scaber leaves P. macrocarpa leaves PI3K/AKT/mTOR |
| title | The combination of Elephantopus scaber and Phaleria macrocarpa leaves extract promotes anticancer activity via downregulation of ER-α, Nrf2 and PI3K/AKT/mTOR pathway |
| title_full | The combination of Elephantopus scaber and Phaleria macrocarpa leaves extract promotes anticancer activity via downregulation of ER-α, Nrf2 and PI3K/AKT/mTOR pathway |
| title_fullStr | The combination of Elephantopus scaber and Phaleria macrocarpa leaves extract promotes anticancer activity via downregulation of ER-α, Nrf2 and PI3K/AKT/mTOR pathway |
| title_full_unstemmed | The combination of Elephantopus scaber and Phaleria macrocarpa leaves extract promotes anticancer activity via downregulation of ER-α, Nrf2 and PI3K/AKT/mTOR pathway |
| title_short | The combination of Elephantopus scaber and Phaleria macrocarpa leaves extract promotes anticancer activity via downregulation of ER-α, Nrf2 and PI3K/AKT/mTOR pathway |
| title_sort | combination of elephantopus scaber and phaleria macrocarpa leaves extract promotes anticancer activity via downregulation of er α nrf2 and pi3k akt mtor pathway |
| topic | Anticancer Apoptosis Combination extract E. scaber leaves P. macrocarpa leaves PI3K/AKT/mTOR |
| url | http://www.sciencedirect.com/science/article/pii/S0975947622001334 |
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