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.
Keywords: Thyroid cancer, Lithospermum officinale, Shikonin, apoptosis, Autophagy, Drug resistance, Toxicological study.
[http://dx.doi.org/10.21037/jtd.2019.08.37] [PMID: 33145090]
[http://dx.doi.org/10.1016/j.path.2019.08.002] [PMID: 31672298]
[http://dx.doi.org/10.3803/EnM.2016.31.3.392] [PMID: 27586449]
[http://dx.doi.org/10.1210/er.2019-00007] [PMID: 31322645]
[PMID: 28197471]
[http://dx.doi.org/10.1056/NEJMra042972] [PMID: 15745981]
[http://dx.doi.org/10.1097/MNM.0000000000000132] [PMID: 24751702]
[http://dx.doi.org/10.1056/NEJMoa2005651] [PMID: 32846061]
[http://dx.doi.org/10.1056/NEJMoa1406470] [PMID: 25671254]
[http://dx.doi.org/10.1200/JCO.2012.48.4659] [PMID: 24002501]
[http://dx.doi.org/10.1016/j.beem.2017.04.012] [PMID: 28911730]
[http://dx.doi.org/10.1016/S1470-2045(12)70335-2] [PMID: 22898678]
[http://dx.doi.org/10.3389/fphar.2020.00891] [PMID: 32595510]
[http://dx.doi.org/10.3322/caac.21184] [PMID: 23716430]
[http://dx.doi.org/10.1002/cncr.10245] [PMID: 11900238]
[http://dx.doi.org/10.1002/jcp.27442] [PMID: 30317564]
[http://dx.doi.org/10.1016/j.pmrj.2010.03.024] [PMID: 20656618]
[http://dx.doi.org/10.1002/cncr.31790] [PMID: 30602059]
[http://dx.doi.org/10.6116/kjh.2013.28.2.67]
[http://dx.doi.org/10.1055/s-0033-1350934] [PMID: 24155261]
[http://dx.doi.org/10.1016/S0040-4039(00)71917-4]
[http://dx.doi.org/10.2478/s11756-006-0077-x]
[PMID: 14206230]
[http://dx.doi.org/10.12659/MSM.908381] [PMID: 29389913]
[http://dx.doi.org/10.1210/jc.2013-2583] [PMID: 24106286]
[http://dx.doi.org/10.3892/mmr.2016.4967] [PMID: 26935754]
[http://dx.doi.org/10.1371/journal.pone.0052706] [PMID: 23300986]
[http://dx.doi.org/10.5487/TR.2015.31.4.403] [PMID: 26877842]
[http://dx.doi.org/10.5487/TR.2015.31.1.077] [PMID: 25874036]