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 (HBEGF)-
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.

Title

International journal of molecular sciences

Publisher

MDPI

Publisher Country

Switzerland

Indexing

Thomson Reuters

Impact Factor

5.9

Publication Type

Prtinted only

Volume

22

Year

2021

Pages

8151