Abstract
Endoxifen, an active metabolite of tamoxifen, has been shown to be an effective anti-estrogenic agent in estrogen receptor-positive breast cancer patients. In melanoma, estrogen receptor expression is shown to be associated with disease progression. However, the therapeutic benefit of endoxifen in melanoma has not yet been evaluated. Here, we present the first demonstration of the anti-melanogenic activity of endoxifen in vitro and in vivo.The in vitro cytotoxic effect of endoxifen was tested using a cell viability assay. The in vivo anti-melanogenic activity was evaluated in B16F10 cell-bearing C57BL/6 mice, a mouse melanoma model. The general toxicity was tested in Swiss albino mice.Endoxifen exhibited greater activity against melanoma cell lines. Treatment of B16F10 mouse and SK-MEL-5 human melanoma cell lines with 10 μM of endoxifen for 48 h respectively resulted in 93.6 and 92.5% cell death. Orally administered endoxifen, at dose levels of 4 and 8 mg/kg body weight/day for 20 consecutive days, respectively reduced metastatic melanoma nodules in the lungs by 26.7 and 82.7%.Endoxifen was found to be a safe and effective anti-melanogenic agent in animal studies.
Highlights
The presence of estrogen receptor (ER) in melanoma cells prompted research on the potential to use selective estrogen receptor modulators such as tamoxifen to treat patients with melanoma [1, 2]
In vitro anti-melanogenic activity Treatment with endoxifen at 10 μM for 48 h resulted in significant cell death across all melanoma cell lines tested (Fig. 1)
In vivo anti-melanogenic activity The anti-melanoma efficacy of endoxifen was tested in B16F10 melanoma-bearing C57BL/6 mice
Summary
The presence of estrogen receptor (ER) in melanoma cells prompted research on the potential to use selective estrogen receptor modulators such as tamoxifen to treat patients with melanoma [1, 2]. Clinical studies showed some clinical benefit, especially when used in combination with other therapeutics [3]. With the growth in understanding of the importance of cytochrome P450 2D6 (CYP2D6) polymorphism and its relationship with the therapeutic outcome of tamoxifen in patients with breast cancer [6], we can partly attribute the unpredictable results from early melanoma studies to CYP2D6 polymorphism [7]. Drug–drug interactions have been shown to affect tamoxifen activity. The effectiveness of endoxifen, an active metabolite of tamoxifen, is independent of CYP2D6, and its unique therapeutic benefit was recently confirmed in patients with breast cancer [8, 9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
