Essential Oil of <i>Mentha aquatica var. Kenting Water Mint</i> Suppresses Two-Stage Skin Carcinogenesis Accelerated by BRAF Inhibitor Vemurafenib
The v-raf murine sarcoma viral homolog B1 (BRAF) inhibitor drug vemurafenib (PLX4032) is used to treat melanoma; however, epidemiological evidence reveals that it could cause cutaneous keratoacanthomas and squamous cell carcinoma in cancer patients with the most prevalent <i>HRAS<sup>Q61...
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MDPI AG
2019-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/12/2344 |
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| author | Chih-Ting Chang Wen-Ni Soo Yu-Hsin Chen Lie-Fen Shyur |
| author_facet | Chih-Ting Chang Wen-Ni Soo Yu-Hsin Chen Lie-Fen Shyur |
| author_sort | Chih-Ting Chang |
| collection | DOAJ |
| description | The v-raf murine sarcoma viral homolog B1 (BRAF) inhibitor drug vemurafenib (PLX4032) is used to treat melanoma; however, epidemiological evidence reveals that it could cause cutaneous keratoacanthomas and squamous cell carcinoma in cancer patients with the most prevalent <i>HRAS<sup>Q61L</sup></i> mutation. In a two-stage skin carcinogenesis mouse model, the skin papillomas induced by 7,12-dimethylbenz[a]anthracene (DMBA)/12-<i>O</i>-tetradecanoylphorbol-13-acetate (TPA) (DT) resemble the lesions in BRAF inhibitor-treated patients. In this study, we investigated the bioactivity of <i>Mentha aquatica var. Kenting Water Mint</i> essential oil (KWM-EO) against PDV cells, mouse keratinocytes bearing <i>HRAS<sup>Q61L</sup></i> mutation, and its effect on inhibiting papilloma formation in a two-stage skin carcinogenesis mouse model with or without PLX4032 co-treatment. Our results revealed that KWM-EO effectively attenuated cell viability, colony formation, and the invasive and migratory abilities of PDV cells. Induction of G<sub>2</sub>/M cell-cycle arrest and apoptosis in PDV cells was also observed. KWM-EO treatment significantly decreased the formation of cutaneous papilloma further induced by PLX4032 in DT mice (DTP). Immunohistochemistry analyses showed overexpression of keratin14 and COX-2 in DT and DTP skin were profoundly suppressed by KWM-EO treatment. This study demonstrates that KWM-EO has chemopreventive effects against PLX4032-induced cutaneous side-effects in a DMBA/TPA-induced two-stage carcinogenesis model and will be worth further exploration for possible application in melanoma patients. |
| first_indexed | 2024-12-19T10:05:50Z |
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| language | English |
| last_indexed | 2024-12-19T10:05:50Z |
| publishDate | 2019-06-01 |
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| series | Molecules |
| spelling | doaj.art-0443d4f3ad85462484b7c8b9034b42b32022-12-21T20:26:31ZengMDPI AGMolecules1420-30492019-06-012412234410.3390/molecules24122344molecules24122344Essential Oil of <i>Mentha aquatica var. Kenting Water Mint</i> Suppresses Two-Stage Skin Carcinogenesis Accelerated by BRAF Inhibitor VemurafenibChih-Ting Chang0Wen-Ni Soo1Yu-Hsin Chen2Lie-Fen Shyur3Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, TaiwanAgricultural Biotechnology Research Center, Academia Sinica, Taipei 115, TaiwanTaichung District Agricultural Research and Extension Station, Council of Agriculture, Executive Yuan, Taichung 515, TaiwanAgricultural Biotechnology Research Center, Academia Sinica, Taipei 115, TaiwanThe v-raf murine sarcoma viral homolog B1 (BRAF) inhibitor drug vemurafenib (PLX4032) is used to treat melanoma; however, epidemiological evidence reveals that it could cause cutaneous keratoacanthomas and squamous cell carcinoma in cancer patients with the most prevalent <i>HRAS<sup>Q61L</sup></i> mutation. In a two-stage skin carcinogenesis mouse model, the skin papillomas induced by 7,12-dimethylbenz[a]anthracene (DMBA)/12-<i>O</i>-tetradecanoylphorbol-13-acetate (TPA) (DT) resemble the lesions in BRAF inhibitor-treated patients. In this study, we investigated the bioactivity of <i>Mentha aquatica var. Kenting Water Mint</i> essential oil (KWM-EO) against PDV cells, mouse keratinocytes bearing <i>HRAS<sup>Q61L</sup></i> mutation, and its effect on inhibiting papilloma formation in a two-stage skin carcinogenesis mouse model with or without PLX4032 co-treatment. Our results revealed that KWM-EO effectively attenuated cell viability, colony formation, and the invasive and migratory abilities of PDV cells. Induction of G<sub>2</sub>/M cell-cycle arrest and apoptosis in PDV cells was also observed. KWM-EO treatment significantly decreased the formation of cutaneous papilloma further induced by PLX4032 in DT mice (DTP). Immunohistochemistry analyses showed overexpression of keratin14 and COX-2 in DT and DTP skin were profoundly suppressed by KWM-EO treatment. This study demonstrates that KWM-EO has chemopreventive effects against PLX4032-induced cutaneous side-effects in a DMBA/TPA-induced two-stage carcinogenesis model and will be worth further exploration for possible application in melanoma patients.https://www.mdpi.com/1420-3049/24/12/2344BRAF inhibitor<i>Mentha aquatica var. Kenting Water Mint</i>essential oilchemopreventiontwo-stage skin carcinogenesis |
| spellingShingle | Chih-Ting Chang Wen-Ni Soo Yu-Hsin Chen Lie-Fen Shyur Essential Oil of <i>Mentha aquatica var. Kenting Water Mint</i> Suppresses Two-Stage Skin Carcinogenesis Accelerated by BRAF Inhibitor Vemurafenib Molecules BRAF inhibitor <i>Mentha aquatica var. Kenting Water Mint</i> essential oil chemoprevention two-stage skin carcinogenesis |
| title | Essential Oil of <i>Mentha aquatica var. Kenting Water Mint</i> Suppresses Two-Stage Skin Carcinogenesis Accelerated by BRAF Inhibitor Vemurafenib |
| title_full | Essential Oil of <i>Mentha aquatica var. Kenting Water Mint</i> Suppresses Two-Stage Skin Carcinogenesis Accelerated by BRAF Inhibitor Vemurafenib |
| title_fullStr | Essential Oil of <i>Mentha aquatica var. Kenting Water Mint</i> Suppresses Two-Stage Skin Carcinogenesis Accelerated by BRAF Inhibitor Vemurafenib |
| title_full_unstemmed | Essential Oil of <i>Mentha aquatica var. Kenting Water Mint</i> Suppresses Two-Stage Skin Carcinogenesis Accelerated by BRAF Inhibitor Vemurafenib |
| title_short | Essential Oil of <i>Mentha aquatica var. Kenting Water Mint</i> Suppresses Two-Stage Skin Carcinogenesis Accelerated by BRAF Inhibitor Vemurafenib |
| title_sort | essential oil of i mentha aquatica var kenting water mint i suppresses two stage skin carcinogenesis accelerated by braf inhibitor vemurafenib |
| topic | BRAF inhibitor <i>Mentha aquatica var. Kenting Water Mint</i> essential oil chemoprevention two-stage skin carcinogenesis |
| url | https://www.mdpi.com/1420-3049/24/12/2344 |
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