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Ethyl P-Methoxycinnamate: An Active Anti-Metastasis Agent and Chemosensitizer Targeting NFκB from Kaempferia galanga for Melanoma Cells
The most common type of skin cancer is melanoma. While significant advances in chemotherapy have occurred in a few instances, only marginal progress has been made in treating metastatic melanoma. Natural medicine has traditionally been used to treat various illnesses, including cancer. The purpose o...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8950268/ https://www.ncbi.nlm.nih.gov/pubmed/35330088 http://dx.doi.org/10.3390/life12030337 |
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author | Lallo, Subehan Hardianti, Besse Sartini, Sartini Ismail, Ismail Laela, Dewi Hayakawa, Yoshihiro |
author_facet | Lallo, Subehan Hardianti, Besse Sartini, Sartini Ismail, Ismail Laela, Dewi Hayakawa, Yoshihiro |
author_sort | Lallo, Subehan |
collection | PubMed |
description | The most common type of skin cancer is melanoma. While significant advances in chemotherapy have occurred in a few instances, only marginal progress has been made in treating metastatic melanoma. Natural medicine has traditionally been used to treat various illnesses, including cancer. The purpose of this study was to identify the active compound in Kaempferia galanga, which could be used to treat melanoma as an anti-metastasis and chemosensitizer agent. The active compound in K. galanga was isolated and identified using chromatography and spectroscopy techniques, and given six compounds. Inhibitory activity on NFκB activation and cell viability was determined using reporter assay methods. Among the isolated compounds, ethyl p-methoxycinnamate (EPMC) demonstrated potent NFκB inhibitory activity against melanoma cell B16F10- NFκB Luc2 with an IC50 of 88.7 μM. Further investigation was conducted by evaluating the anti-metastasis effect of EPMC in vitro by using wound-healing assays, invasion tests, and molecular mechanism assays using Western blotting. NFκB has been implicated in tumorigenesis through the PI3K/Akt/NFκB pathway. The results of this study indicated that EPMCs act as inhibitors of p38 and thereby Akt phosphorylation inhibitors at serine 473, inhibiting NFκB-dependent transcription. Further analysis with paclitaxel demonstrated that the combinations could sensitize to apoptosis in response to well-known chemotherapy agents. Additional studies were conducted using the human melanoma cancer cell line SK-Mel 28. Along with the induction of apoptosis, we observed an increase in p-γH2AX expression (a molecular marker for double strand breaks in DNA damage) in response to treatment with paclitaxel and EPMC. The result showed EPMC to be a potential, viable adjuvant for improving the clinical efficacy of anti-metastatic and cancer chemotherapy. |
format | Online Article Text |
id | pubmed-8950268 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89502682022-03-26 Ethyl P-Methoxycinnamate: An Active Anti-Metastasis Agent and Chemosensitizer Targeting NFκB from Kaempferia galanga for Melanoma Cells Lallo, Subehan Hardianti, Besse Sartini, Sartini Ismail, Ismail Laela, Dewi Hayakawa, Yoshihiro Life (Basel) Article The most common type of skin cancer is melanoma. While significant advances in chemotherapy have occurred in a few instances, only marginal progress has been made in treating metastatic melanoma. Natural medicine has traditionally been used to treat various illnesses, including cancer. The purpose of this study was to identify the active compound in Kaempferia galanga, which could be used to treat melanoma as an anti-metastasis and chemosensitizer agent. The active compound in K. galanga was isolated and identified using chromatography and spectroscopy techniques, and given six compounds. Inhibitory activity on NFκB activation and cell viability was determined using reporter assay methods. Among the isolated compounds, ethyl p-methoxycinnamate (EPMC) demonstrated potent NFκB inhibitory activity against melanoma cell B16F10- NFκB Luc2 with an IC50 of 88.7 μM. Further investigation was conducted by evaluating the anti-metastasis effect of EPMC in vitro by using wound-healing assays, invasion tests, and molecular mechanism assays using Western blotting. NFκB has been implicated in tumorigenesis through the PI3K/Akt/NFκB pathway. The results of this study indicated that EPMCs act as inhibitors of p38 and thereby Akt phosphorylation inhibitors at serine 473, inhibiting NFκB-dependent transcription. Further analysis with paclitaxel demonstrated that the combinations could sensitize to apoptosis in response to well-known chemotherapy agents. Additional studies were conducted using the human melanoma cancer cell line SK-Mel 28. Along with the induction of apoptosis, we observed an increase in p-γH2AX expression (a molecular marker for double strand breaks in DNA damage) in response to treatment with paclitaxel and EPMC. The result showed EPMC to be a potential, viable adjuvant for improving the clinical efficacy of anti-metastatic and cancer chemotherapy. MDPI 2022-02-24 /pmc/articles/PMC8950268/ /pubmed/35330088 http://dx.doi.org/10.3390/life12030337 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lallo, Subehan Hardianti, Besse Sartini, Sartini Ismail, Ismail Laela, Dewi Hayakawa, Yoshihiro Ethyl P-Methoxycinnamate: An Active Anti-Metastasis Agent and Chemosensitizer Targeting NFκB from Kaempferia galanga for Melanoma Cells |
title | Ethyl P-Methoxycinnamate: An Active Anti-Metastasis Agent and Chemosensitizer Targeting NFκB from Kaempferia galanga for Melanoma Cells |
title_full | Ethyl P-Methoxycinnamate: An Active Anti-Metastasis Agent and Chemosensitizer Targeting NFκB from Kaempferia galanga for Melanoma Cells |
title_fullStr | Ethyl P-Methoxycinnamate: An Active Anti-Metastasis Agent and Chemosensitizer Targeting NFκB from Kaempferia galanga for Melanoma Cells |
title_full_unstemmed | Ethyl P-Methoxycinnamate: An Active Anti-Metastasis Agent and Chemosensitizer Targeting NFκB from Kaempferia galanga for Melanoma Cells |
title_short | Ethyl P-Methoxycinnamate: An Active Anti-Metastasis Agent and Chemosensitizer Targeting NFκB from Kaempferia galanga for Melanoma Cells |
title_sort | ethyl p-methoxycinnamate: an active anti-metastasis agent and chemosensitizer targeting nfκb from kaempferia galanga for melanoma cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8950268/ https://www.ncbi.nlm.nih.gov/pubmed/35330088 http://dx.doi.org/10.3390/life12030337 |
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