Title:Research Progress of the Molecular Mechanism of Antithyroid Cancer Activity
of Shikonin
Volume: 17
Author(s): Chunguang Sun and Lin Liao*
Affiliation:
- Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial
Qianfoshan Hospital, Jinan, Shandong, 250024, China
Keywords:
Thyroid cancer, Lithospermum officinale, Shikonin, apoptosis, Autophagy, Drug resistance, Toxicological study.
Abstract: Thyroid cancer is one of the most common endocrine neoplasms. Treatment methods include surgical resection, radioactive iodine therapy,
inhibition of thyroid-stimulating hormone, and inhibition of kinase-based target therapies. These treatments induced adverse effects. Lithospermum
officinale possesses antioxidant, anticancer, burn-healing, and anti-inflammatory activities, and Shikonin is the main ingredient. Antithyroid cancer
studies of Shikonin discovered that it inhibited thyroid cancer cell migration and invasion by suppressing the epithelial-mesenchymal transition;
induced cell cycle arrest; induced DNA damage and apoptosis by producing excessive reactive oxygen species; upregulated Bax; increased the
stability of p53; decreased the expression of Mdm2; downregulated Slug and MMP-2, MMP-9, and MMP-14; repressed the phosphorylation of Erk
and Akt; activated the p16/retinoblastoma protein pathway, leading to apoptosis; suppressed the expression of DNMT1; reduced the PTEN gene
methylation; increased the expression of PTEN, leading to the inhibition of migration; increased LC3-II to induce autophagy and apoptosis of
medullary thyroid carcinoma; and upregulated βII-tubulin in the cell to produce less resistance to cisplatin and paclitaxel, without cross-resistance
to other anticancer agents. In vivo studies showed that it is safe in Sprague-Dawley rats, Beagle dogs, and nude mice.
