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

Abstract

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.

Dual action effects of ethyl-p-methoxycinnamate against dengue virus infection and inflammation via NF-κB pathway suppression

“…For instance, KG extracts have exhibited their anti-inflammatory and cytoprotective effects by targeting NF-κB activity 44 . Furthermore, EPMC has been identified as an anti-metastatic and chemosensitizing agent through its capacity to inhibit NF-κB activation in melanoma cells 45 . In a rat model of carrageenan-induced edema, which simulates an acute inflammatory condition, EPMC derived from KG extracts emerged as an active anti-inflammatory agent 24 .…”

Piper retrofractum ameliorates imiquimod-induced skin inflammation via modulation of TLR4 axis and suppression of NF-κB activity

“…The viability of the cells was determined according to Ref. [ 21 ]. Briefly, 2 × 10 4 cells/well of RAW264.7 cells or RAW264.7-NFκB-Luc2 cells were plated in a 96 well plate and incubated for 24 h. The cells were treated with 50 μM of compound or 50 μg/mL of extract followed by 24 h incubation.…”

“…IVIS LUMINA II and Living Image 4.2 software (Caliper Life Science) were used to measure the luciferase activity via determination of the light that the cells released. Luciferase activity was demonstrated as photons/seconds, and the formula (extracts total flux divided by vehicle total flux) was used to quantified the fold of NFκB activity [ 20 , 21 ].…”

Validation of High-Performance Liquid Chromatography (HPLC) Method for Quantification of Ethyl p-Methoxycinnamate in Kaempferia galanga Extract

“…EPMC isolated from Kaempferia galanga has anti-inflammatory activity by reducing the leukotriene B4 (LTB4) production in the rats 36 . EPMC also was found to be potential as anti-metastatic and cancer therapy by targeting NFκB 37 . Kaempferia galanga extract has been formulated into several dosage forms, such as hydrogel-containing extract emulsion, lozenge, sunscreen, and other pharmaceutical dosage forms 38,39,40 .…”