shikonin and plumbagin

Quinones are plant-derived secondary metabolites that present some anti-proliferation and anti-metastasis effects in various cancer types both in vitro and in vivo. This review focuses on the anti-cancer prospects of plant-derived quinones, namely, aloe-emodin, juglone, β-lapachol, plumbagin, shikonin, and thymoquinone. We intend to summarize their anti-cancer effects and investigate the mechanism of actions to promote the research and development of anti-cancer agents from quinones.

Topics: Anthraquinones; Antineoplastic Agents, Phytogenic; Benzoquinones; Cell Line, Tumor; Cell Survival; Humans; Naphthoquinones; Neoplasms; Plant Extracts

Topics: Antineoplastic Agents; cdc25 Phosphatases; Cell Line, Tumor; Cell Survival; Enzyme Inhibitors; Humans; MAP Kinase Kinase 7; Models, Molecular; Molecular Docking Simulation; Naphthoquinones

Plumbagin and shikonin, plant metabolites which have naphthoquinone structures, induced mammalian topoisomerase II-mediated DNA cleavage in vitro. Treatment of a reaction mixture containing these naphthoquinones and topoisomerase II at an elevated temperature (65 degrees C) resulted in a great reduction in DNA cleavage, suggesting that the mechanism of the topoisomerase II-mediated DNA cleavage induced by these naphthoquinones is through formation of a cleavable complex, as seen with antitumor agents such as 4'-(9-acridinylamino)methanesulfon-m-anisidide and demethylepipodophyllotoxin ethylidene-beta-glucoside. Lawson and lapacol, which are structurally related plant metabolites with naphthoquinone moieties, could not induce topoisomerase II-mediated DNA cleavage. Plumbagin and shikonin induced a similar DNA cleavage pattern with topoisomerase II which was different from the cleavage patterns induced with other known topoisomerase II-active drugs. A DNA-unwinding assay with T4 DNA ligase showed that shikonin, lawson, and lapacol did not intercalate into DNA, while plumbagin and 2-methyl-1,4-naphthoquinone intercalate into DNA, but to a lower degree than 4'-(9-acridinylamino)methanesulfon-m-anisidide does.

Topics: Animals; Antineoplastic Agents, Phytogenic; DNA Damage; DNA Topoisomerases, Type II; Drug Synergism; Enzyme Induction; Intercalating Agents; Mice; Mice, Inbred BALB C; Naphthoquinones