Shikonin is a naturally occurring compound found in Gromwell roots, traditionally used in Chinese medicine for various purposes. Interestingly, shikonin and the related naphthoquinone compounds are responsible for the red/purple color of the roots. Studies have shown that shikonin itself has antibacterial, anti-inflammatory, and anti-tumor effects. Recently, a new study investigated the effects on brain tumors.
The difficulty in treating brain tumors is the presence of the blood-brain barrier and also the blood-tumor barrier. These barriers prevent most small molecules from crossing, and therefore brain tumors are protected from most chemical treatments. Furthermore, the current standard treatment for glioblastoma includes chemotherapy with temozolomide, however, the glioblastoma cells very quickly develop resistance to this chemical.
In vitro studies showed that shikonin does inhibit glioblastoma cells quite effectively. Therfore, an alternative method of delivery was attempted to cross the barriers. First, lab mice were infused with cancer cells directly into the thalamus. Next, direct intracranial infusion of shikonin was applied into the same spot. By this method, the blood-brain and blood-tumor barriers are physically passed through by the injection needle. In this way, the effect of the treatment in a living system can be observed.
For this study, 2 different brain cancer cell lines were used. The mice from either group, when treated with shikonin, showed significantly longer survival times. Some of the mice were treated with combination of shikonin and temozolomide or temozolomide alone. The effects of the combination treatments were inconclusive. Once cancer cell line seemed to have even better success with a combination treatment, but the other line did not. In addition, neither cancer line, when treated with temozolomide alone, showed significant improvement.
Although shikonin has poor bioavailability and cannot cross the blood-brain barrier on its own, most chemical treatments will face the same problem. Therefore, using direct intracranial infusion may help develop more effective treatment for brain tumors.
Maeoka, R, Ouji Y, Nakazawa T, et al. Local administration of shikonin improved the overall survival in orthotopic murine glioblastoma models with temozolomide resistance. Biomed Pharmacother. 2023 Oct:166:115296. PMID: 37557011