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Open AccessArticle

Essential Oil of Mentha aquatica var. Kenting Water Mint Suppresses Two-Stage Skin Carcinogenesis Accelerated by BRAF Inhibitor Vemurafenib

1
Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan
2
Department of Biological Science and Technology, National Taiwan University, Taipei 106, Taiwan
3
Taichung District Agricultural Research and Extension Station, Council of Agriculture, Executive Yuan, Taichung 515, Taiwan
4
Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei 110, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: Kyoko Nakagawa-Goto
Molecules 2019, 24(12), 2344; https://doi.org/10.3390/molecules24122344
Received: 29 May 2019 / Revised: 21 June 2019 / Accepted: 22 June 2019 / Published: 25 June 2019
(This article belongs to the Special Issue Antitumor and Anti-HIV Agents from Natural Products)
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 HRASQ61L mutation. In a two-stage skin carcinogenesis mouse model, the skin papillomas induced by 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) (DT) resemble the lesions in BRAF inhibitor-treated patients. In this study, we investigated the bioactivity of Mentha aquatica var. Kenting Water Mint essential oil (KWM-EO) against PDV cells, mouse keratinocytes bearing HRASQ61L 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 G2/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. View Full-Text
Keywords: BRAF inhibitor; Mentha aquatica var. Kenting Water Mint; essential oil; chemoprevention; two-stage skin carcinogenesis BRAF inhibitor; Mentha aquatica var. Kenting Water Mint; essential oil; chemoprevention; two-stage skin carcinogenesis
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Chang, C.-T.; Soo, W.-N.; Chen, Y.-H.; Shyur, L.-F. Essential Oil of Mentha aquatica var. Kenting Water Mint Suppresses Two-Stage Skin Carcinogenesis Accelerated by BRAF Inhibitor Vemurafenib. Molecules 2019, 24, 2344.

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Molecules, EISSN 1420-3049, Published by MDPI AG
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