NatuChral quinones are secondary metabolites of plant and are categorized as benzoquinone, naphthoquinone, phenanthrenequinone, and anthraonic inflammation leads to tumor formation. Metastasis of oral cancer has long been a challenge since it can easily colonize in lung through the lymphatic system. We identify isoplumbagin, a natural quinone according to their aromatic carbon skeleton . Quinones are highly electrophilic molecules that accept one- or two-electrons from flavoenzymes and iron-sulfur proteins to form semiquinon, as an anti-cancer chemical for oral squamous cell carcinoma (OSCC), glioblastoma, non-small cell lung carcinoma, prostate and cervical cancers. Isoplumbagin also reduces tumor formation in the in vivo or thydroquinone. They exert cytotoxic effects through alkylating proteins or DNA and affect the redox cycle with their semiquinone radicals to generate reactive oxygen speciesotopic OSCC tumor-bearing mice model. Mechanistically, we find that isoplumbagin acts as a substrate of NAD(P)H quinone dehydrogenase 1 (NQO1) protein, leading to mitochondrial fusion, and reduced mitochondrial respiration.
Medicinal plants and their metabolites are great sources for pharmaceutical applications. The metabolites in plants provide a rich variety of bioactive compounds with anticancer, antioxidant, anti-inflammatory, or antimicrobial activities. Some of these drugs such as paclitaxel, docetaxel, resveratrol, vincristine, and vinblastine are approved of and used extensively in treating several types of cancer, including breast, head and neck, testicular, and bladder cancers . Natural quinones are secondary metabolites of plant and are categorized as benzoquinone, naphthoquinone, phenanthrenequinone, and anthraquinone according to their aromatic carbon skeleton . Quinones are highly electrophilic molecules that accept one- or two-electrons from flavoenzymes and iron-sulfur proteins to form semiquinone or hydroquinone. They exert cytotoxic effects through alkylating proteins or DNA and affect the redox cycle with their semiquinone radicals to generate reactive oxygen species. Their cytotoxicity promotes inflammatory reactions, oxidizes DNA, and induces cell death. Quinone-based drugs such as doxorubicin and mitomycin C have been used clinically for cancer chemotherapy, but their adverse side effects and toxicity have been an issue . Consequently, there is a continued search for the development of quinone-based agents displaying antitumor activity that are less toxic and have reduced side effects.
Isoplumbagin (5-hydroxy-3-methyl-1,4-naphthoquinone) can be isolated from the bark of Lawsonia inermis  and Plumbago europaea  and has been shown to exhibit anti-inflammatory activity against Carrageenan-induced rat paw oedema  and antimicrobial activity against invasive vaginitis strains . Chronic inflammation facilitates the initiation and progression of cancer .
Figure 1. Schematic summary of the molecular mechanisms of isoplumbagin-mediated anti-cancer effect.