Inhibition of IKK complex by (2 methyl butyryl) Shikonin, a naturally occurring naphthoquinone, abrogates melanoma growth and progression via modulation of the IKK/NFκB /EMT signaling axis

Melanoma is an aggressive form of malignancy that originates from melanin-producing cells known as melanocytes underlying the basal layer of the epidermis with a poor prognosis, low survival rates, and limited treatment options. Although several specific and effective systematic strategies for treating melanoma have been established, the underlying molecular mechanism of melanoma progression, mortality and the promising therapeutic options remain elusive. Shikonin (SK), a natural naphthoquinone derived from a medicinal herbaceous plant, has been shown to inhibit the proliferation of several cancer cells. However, its role in the context of melanoma is poorly understood. In the present study, the anti-melanoma activity of (2-methylbutyryl) Shikonin was assessed under in vitro and in vivo models. In vitro findings revealed that (2-methylbutyryl) Shikonin significantly reduced the viability and promoted apoptosis in the B16F10 melanoma cells. Additionally (2-methylbutyryl) Shikonin significantly suppressed migration and invasion of melanoma cells by regulating IKK/NFκB/EMT signalling axis thereby attenuating nuclear translocation and subsequent transcription of NF-κB downstream target genes. Furthermore, (2-methylbutyryl) Shikonin administration significantly reduced tumor size and weight in the xenograft melanoma mice model. Our data presents novel insights that justify additional preclinical and clinical validations of (2-methylbutyryl) Shikonin for melanoma therapy.