Abstract P44: The Anti-Melanoma Activity of (2 Methyl Buturyl) Shikonin, a Naturally Occurring Naphthoquinone is Attributed to Modulation of the IKK/ NFκB /EMT Signaling axis, Attenuating NF-κB Nuclear translocation and Transcription of Downstream Target genes

Abstract Melanoma originates from melanin-producing cells known as melanocytes underlying basal layer of the epidermis. Melanoma is an aggressive malignancy with a poor prognosis, low survival rates, and limited options of treatment. Melanoma poses a serious threat with lethal consequences because of its rapid capacity to spread and to invade new organs. Although several specific and effective strategies for treating melanoma have been established, the key cause of death 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 inhibiting the melanoma progression and metastasis is not well understood. In the present study, the anti-melanoma activity of (2-methylbutyryl) Shikonin was assessed in In-vitro and In-vivo models. The findings revealed that (2-methylbutyryl) Shikonin significantly reduced the viability of Melanoma cells while causing less cytotoxicity to normal skin cell types. Shikonin also decreased the growth and promoted apoptosis of the B16F10 melanoma cell line via activating the apoptosis signaling pathway. Shikonin suppressed cell migration and invasion, increased E-cadherin levels, decreased N-cadherin and vimentin levels, and reversed EMT by inhibiting activation of IKK/ NFκB/EMT signalling axis, attenuating NFκB nuclear accumulation, and transcription of targeted EMT-related genes. Furthermore, (2-methylbutyryl) Shikonin administration dramatically reduced tumor size and weight in the xenographt melanoma model while exhibiting no major adverse manifestations to nude mice. Together, our data presents some novel insights that justify additional preclinical and clinical studies of (2-methylbutyryl) Shikonin for melanoma therapy. Citation Format: Aalim Maqsood Bhat, and Sheikh A Tasduq. The Anti-Melanoma Activity of (2 Methyl Buturyl) Shikonin, a Naturally Occurring Naphthoquinone is Attributed to Modulation of the IKK/ NFκB /EMT Signaling axis, Attenuating NF-κB Nuclear translocation and Transcription of Downstream Target genes abstract. In: Proceedings of Frontiers in Cancer Science 2024; 2024 Nov 13-15; Singapore. Philadelphia (PA): AACR; Cancer Res 2025;85 (15Suppl): Abstract nr P44.