Shikonin

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.

The present study was designed to prepare co-encapsulated with shikonin/doxorubicin pH-sensitive liposomes (SHK/DOX-pHSL) and investigate their synergistic anti-cancer effect in drug-resistant breast cancer cells. SHK/DOX-pHSL exhibited a mean diameter of around 145 nm, with a polydispersity index about 0.25. SHK/DOX-pHSL displayed high encapsulation efficiency, good colloidal stability, and sustained-release property. The cumulative release rates of DOX and SHK from SHK/DOX-pHSL were significantly higher in pH 5.0 than those in pH 7.4. In vitro the results showed that SHK/DOX-pHSL could inhibit cell proliferation, migration, invasion, and promoting cell apoptosis. The further studies revealed that SHK/DOX-pHSL could significantly promote cell apoptosis by regulating the expression of Bax and Bcl-2. Moreover, SHK/DOX-pHSL could reverse multidrug resistance (MDR) in MCF-7/ADR cells by inhibiting the expression of MDR1, ABCG2, and MRP1. SHK/DOX-pHSL was successfully prepared and possessed good physical characteristics, which had strong synergistic anti-cancer efficacy and reversed MDR effect in breast cancer cells. Therefore, the novel co-loaded drugs liposomes can provide the basis for further in vivo anti-cancer experiments.