Malignant melanoma is one of the most deadly skin cancer, due to its aggressive proliferation and metastasis. Naringenin, abundantly present in citrus fruits, has widely studied in cancer therapy. In this study, we investigated whether naringenin also has anticancer effects against B16F10 murine and SK-MEL-28 human melanoma cells. Moreover, we assessed the effects of naringenin treatment on angiogenesis of HUVECs and
ex vivo
sprouting of microvessels.Naringenin inhibited tumor cell proliferation and migration in a dose-dependent manner in B16F10 and SK-MEL-28 cells, which is supported by the results that phosphorylation of ERK1/2 and JNK MAPK decreased. Furthermore, naringenin induced cell apoptosis. Western blot analysisshowed naringenin treatment significantly upregulated the protein expression of activated cas3 and PARP in B16F10 and SK-MEL-28 cells. In addition,
in vitro
and
ex vivo
angiogenesis assays demonstrated that naringenin treatment potently suppressed EC migration, tube formation, and sprouting of microvessels. RT-PCR analysis showed that naringenin treatment significantly reduced the mRNA expression of Tie2, but did not inhibit the expression of Ang2. In conclusion, present study demonstrates the anticancer effects of naringenin by its induction of tumor cell death and inhibition of angiogenesis in malignant melanoma, suggesting that naringenin has potential as a safe and effective therapeutic agent to treat melanoma.
Highlights
Diosmetin suppresses the development of DNCB-induced atopic dermatitis.
Diosmetin inhibits the IL-4 induced activation of JAK/STAT pathway.
Diosmetin inhibits the LPS induced activation of ERK, p38 and JNK pathway.
Diosmetin inhibits NO production and iNOS expression by LPS in RAW 264.7 cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.