4.6 Article

Ethyl P-Methoxycinnamate: An Active Anti-Metastasis Agent and Chemosensitizer Targeting NFκB from Kaempferia galanga for Melanoma Cells

Journal

LIFE-BASEL
Volume 12, Issue 3, Pages -

Publisher

MDPI
DOI: 10.3390/life12030337

Keywords

Kampferia galanga; ethyl p-methoxycinnamate (EPMC); p38 alpha; phospho-Akt (Ser473); NF kappa B; B16F10-NF kappa B Luc2; chemosensitizer; anti-metastasis

Funding

  1. Hibah Penelitian Dasar 2021 Kemenristek/BRIN, Indonesian Ministry of Education and Culture
  2. The Ronpaku Program of Japan Science and Promotion of Science [R11815]

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This study identifies ethyl p-methoxycinnamate (EPMC) as a potential compound in Kaempferia galanga for the treatment of melanoma, inhibiting NF kappa B activation and enhancing chemosensitivity. The inhibitory activity of EPMC on p38 and Akt phosphorylation suggests its potential in preventing tumorigenesis via the PI3K/Akt/NF kappa B pathway. Additionally, EPMC shows promise as an adjuvant to enhance the clinical efficacy of anti-metastasis and cancer chemotherapy.
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 NF kappa B activation and cell viability was determined using reporter assay methods. Among the isolated compounds, ethyl p-methoxycinnamate (EPMC) demonstrated potent NF kappa B inhibitory activity against melanoma cell B16F10- NF kappa B Luc2 with an IC50 of 88.7 mu M. 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. NF kappa B has been implicated in tumorigenesis through the PI3K/Akt/NF kappa B pathway. The results of this study indicated that EPMCs act as inhibitors of p38 and thereby Akt phosphorylation inhibitors at serine 473, inhibiting NF kappa B-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-gamma H2AX 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.

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