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Article

Aloysia Citrodora Essential Oil Inhibits Melanoma Cell Growth and Migration by Targeting HB-EGF-EGFR Signaling

1
An-Najah Center for Cancer and Stem Cell Research, Faculty of Medicine and Health Sciences, An-Najah National University, P.O. Box 7, Nablus 99900800, Palestine
2
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus 00970, Palestine
3
Center for Genomic & Regenerative Medicine, School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
4
Department of Immunological Diagnosis, School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
*
Authors to whom correspondence should be addressed.
Academic Editors: Akiko Maeda and Maria Adelaide Caligo
Int. J. Mol. Sci. 2021, 22(15), 8151; https://doi.org/10.3390/ijms22158151
Received: 8 July 2021 / Revised: 22 July 2021 / Accepted: 24 July 2021 / Published: 29 July 2021
(This article belongs to the Special Issue Feature Annual Reviews in Molecular Genetics and Genomics 2021)
Patients diagnosed with melanoma have a poor prognosis due to regional invasion and metastases. The receptor tyrosine kinase epidermal growth factor receptor (EGFR) is found in a subtype of melanoma with a poor prognosis and contributes to drug resistance. Aloysia citrodora essential oil (ALOC-EO) possesses an antitumor effect. Understanding signaling pathways that contribute to the antitumor of ALOC-EO is important to identify novel tumor types that can be targeted by ALOC-EO. Here, we investigated the effects of ALOC-EO on melanoma growth and tumor cell migration. ALOC-EO blocked melanoma growth in vitro and impaired primary tumor cell growth in vivo. Mechanistically, ALOC-EO blocked heparin-binding-epidermal growth factor (HB-EGF)-induced EGFR signaling and suppressed ERK1/2 phosphorylation. Myelosuppressive drugs upregulated HB-EGF and EGFR expression in melanoma cells. Cotreatment of myelosuppressive drugs with ALOC-EO improved the antitumor activity and inhibited the expression of matrix metalloproteinase-7 and -9 and a disintegrin and metalloproteinase domain-containing protein9. In summary, our study demonstrates that ALOC-EO blocks EGFR and ERK1/2 signaling, with preclinical efficacy as a monotherapy or in combination with myelosuppressive drugs in melanoma. View Full-Text
Keywords: melanoma; EGFR; MMP; Aloysia citrodora; HB-EGF; plant; proliferation; metastasis; ERK1/2; herb melanoma; EGFR; MMP; Aloysia citrodora; HB-EGF; plant; proliferation; metastasis; ERK1/2; herb
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MDPI and ACS Style

Salama, Y.; Jaradat, N.; Hattori, K.; Heissig, B. Aloysia Citrodora Essential Oil Inhibits Melanoma Cell Growth and Migration by Targeting HB-EGF-EGFR Signaling. Int. J. Mol. Sci. 2021, 22, 8151. https://doi.org/10.3390/ijms22158151

AMA Style

Salama Y, Jaradat N, Hattori K, Heissig B. Aloysia Citrodora Essential Oil Inhibits Melanoma Cell Growth and Migration by Targeting HB-EGF-EGFR Signaling. International Journal of Molecular Sciences. 2021; 22(15):8151. https://doi.org/10.3390/ijms22158151

Chicago/Turabian Style

Salama, Yousef, Nidal Jaradat, Koichi Hattori, and Beate Heissig. 2021. "Aloysia Citrodora Essential Oil Inhibits Melanoma Cell Growth and Migration by Targeting HB-EGF-EGFR Signaling" International Journal of Molecular Sciences 22, no. 15: 8151. https://doi.org/10.3390/ijms22158151

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