The Olive Oil Monophenolic Secoiridoid Ligstroside Aglycone Suppresses Melanoma Progression by Targeting the BRAF Signaling Pathway
Melanoma is among the most abundant malignancies in the US and worldwide. Ligstroside aglycone (LA) is a rare extra-virgin olive oil-derived monophenolic secoiridoid with diverse bioactivities. LA dose–response screening at the NCI 60 cancer cells panel identified the high sensitivity of the Malme-3...
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MDPI AG
2025-01-01
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| author | Md Ashiq Mahmud Abu Bakar Siddique Afsana Tajmim Judy Ann King Khalid A. El Sayed |
| author_facet | Md Ashiq Mahmud Abu Bakar Siddique Afsana Tajmim Judy Ann King Khalid A. El Sayed |
| author_sort | Md Ashiq Mahmud |
| collection | DOAJ |
| description | Melanoma is among the most abundant malignancies in the US and worldwide. Ligstroside aglycone (LA) is a rare extra-virgin olive oil-derived monophenolic secoiridoid with diverse bioactivities. LA dose–response screening at the NCI 60 cancer cells panel identified the high sensitivity of the Malme-3M cell line, which harbors a <i>BRAF V600E</i> mutation. Daily oral 10 mg/kg LA exhibited potent in vivo antitumor effects against Malme-3M cells xenograft in a nude mouse model by targeting the BRAF signaling pathway. A human Clariom S microarray analysis of the collected Malme- 3M tumors identified 571 dysregulated genes, with the downregulation of pathways critical for melanoma cells growth and survival. A Western blot analysis of the collected animal tumors further validated the downregulation of the mutated BRAF–MAPK axis, as well as the GPD1 and ELOVL6 expression levels. A histopathological analysis of Malme-3M tumor sections showed extensive focal tumor necrosis in treated mice. An immunofluorescence study of tumor sections showed notable reductions in proliferation marker ki67 and the vasculogenesis marker CD31 in treated tumors. These findings promote LA as a potential nutraceutical lead for the control of the <i>BRAF V600E</i> mutant melanoma. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| series | Molecules |
| spelling | doaj-art-24784159cf804eb5af4f8096cbf5438d2025-01-10T13:18:59ZengMDPI AGMolecules1420-30492025-01-0130113910.3390/molecules30010139The Olive Oil Monophenolic Secoiridoid Ligstroside Aglycone Suppresses Melanoma Progression by Targeting the BRAF Signaling PathwayMd Ashiq Mahmud0Abu Bakar Siddique1Afsana Tajmim2Judy Ann King3Khalid A. El Sayed4Department of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USADepartment of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USADepartment of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USAFoundational and Clinical Sciences Department, Thomas F. Frist, Jr. College of Medicine, Belmont University, 1900 Belmont Boulevard, Nashville, TN 37212, USADepartment of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USAMelanoma is among the most abundant malignancies in the US and worldwide. Ligstroside aglycone (LA) is a rare extra-virgin olive oil-derived monophenolic secoiridoid with diverse bioactivities. LA dose–response screening at the NCI 60 cancer cells panel identified the high sensitivity of the Malme-3M cell line, which harbors a <i>BRAF V600E</i> mutation. Daily oral 10 mg/kg LA exhibited potent in vivo antitumor effects against Malme-3M cells xenograft in a nude mouse model by targeting the BRAF signaling pathway. A human Clariom S microarray analysis of the collected Malme- 3M tumors identified 571 dysregulated genes, with the downregulation of pathways critical for melanoma cells growth and survival. A Western blot analysis of the collected animal tumors further validated the downregulation of the mutated BRAF–MAPK axis, as well as the GPD1 and ELOVL6 expression levels. A histopathological analysis of Malme-3M tumor sections showed extensive focal tumor necrosis in treated mice. An immunofluorescence study of tumor sections showed notable reductions in proliferation marker ki67 and the vasculogenesis marker CD31 in treated tumors. These findings promote LA as a potential nutraceutical lead for the control of the <i>BRAF V600E</i> mutant melanoma.https://www.mdpi.com/1420-3049/30/1/139<i>BRAF V600E</i> mutationELOVL6GPD1ligstroside aglyconemelanomaolive phenolics |
| spellingShingle | Md Ashiq Mahmud Abu Bakar Siddique Afsana Tajmim Judy Ann King Khalid A. El Sayed The Olive Oil Monophenolic Secoiridoid Ligstroside Aglycone Suppresses Melanoma Progression by Targeting the BRAF Signaling Pathway Molecules <i>BRAF V600E</i> mutation ELOVL6 GPD1 ligstroside aglycone melanoma olive phenolics |
| title | The Olive Oil Monophenolic Secoiridoid Ligstroside Aglycone Suppresses Melanoma Progression by Targeting the BRAF Signaling Pathway |
| title_full | The Olive Oil Monophenolic Secoiridoid Ligstroside Aglycone Suppresses Melanoma Progression by Targeting the BRAF Signaling Pathway |
| title_fullStr | The Olive Oil Monophenolic Secoiridoid Ligstroside Aglycone Suppresses Melanoma Progression by Targeting the BRAF Signaling Pathway |
| title_full_unstemmed | The Olive Oil Monophenolic Secoiridoid Ligstroside Aglycone Suppresses Melanoma Progression by Targeting the BRAF Signaling Pathway |
| title_short | The Olive Oil Monophenolic Secoiridoid Ligstroside Aglycone Suppresses Melanoma Progression by Targeting the BRAF Signaling Pathway |
| title_sort | olive oil monophenolic secoiridoid ligstroside aglycone suppresses melanoma progression by targeting the braf signaling pathway |
| topic | <i>BRAF V600E</i> mutation ELOVL6 GPD1 ligstroside aglycone melanoma olive phenolics |
| url | https://www.mdpi.com/1420-3049/30/1/139 |
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