Shikonin a potent phytotherapeutic: a comprehensive review on metabolic reprogramming to overcome drug resistance in cancer

Drug resistance remains a major challenge in cancer therapy, often leading to treatment failure. Metabolic reprogramming, a hallmark of cancer, plays a pivotal role in drug resistance. Phytocompounds, particularly shikonin, a naphthoquinone derived from Lithospermum erythrorhizon, have garnered significant interest as potential alternatives for cancer prevention and treatment. This review focuses on the anticancer properties of shikonin, particularly its ability to modulate metabolic reprogramming and overcome drug resistance. This review, based on extensive searches in databases like PubMed, Web of Science, Google Scholar, and Scopus, highlights shikonin's potential as a therapeutic agent. Shikonin exhibits a wide range of anticancer activities, including induction of apoptosis, autophagy, necroptosis, inhibition of angiogenesis, invasion, and migration, as well as disruption of the cell cycle and promotion of DNA damage. It targets altered cancer cell metabolism to inhibit proliferation and reverse drug resistance, making it a promising candidate for therapeutic development. Preliminary clinical trials suggest that shikonin can enhance the efficacy of established chemotherapeutic agents, immunotherapies, and radiation through additive and synergistic interactions. Despite its promise, further research is needed to elucidate the precise mechanisms underlying shikonin's metabolic reprogramming effects in cancer. A comprehensive understanding could pave the way for its integration into standard oncological treatments. With its capacity to act on multiple cancer pathways and enhance conventional treatments, shikonin stands out as a viable candidate for combating drug-resistant cancers and advancing clinical oncology.