Baicalein induced apoptosis and autophagy of undifferentiated thyroid cancer cells by the ERK/PI3K/Akt pathway

Am J Transl Res. 2019 Jun 15;11(6):3341-3352. eCollection 2019.


Thyroid cancer is the most common endocrine system malignancy, and undifferentiated thyroid cancer is one of the most invasive tumors. Studies have found that baicalein, a major flavonoid separated from the root of Scutellaria baicalensis Georgi, has an inhibitory effect on a variety of malignant tumor cells. However, the effect of baicalein on undifferentiated thyroid cancer has not yet been investigated. In the present study, follicular undifferentiated thyroid cancer cells (FRO) were treated with different concentrations of baicalein (10 μM, 20 μM, 40 μM, 80 μM) for 12 h, 24 h, 36 h, or 48 h; then, the cell viability and clonogenicity were measured. Cell cycles and cell apoptosis were measured by flow cytometer after FRO cells were treated with baicalein for 36 h or 48 h. After FRO cells were treated with baicalein for 48 h, the expression of apoptosis-related proteins (Bcl-2, Bax, Caspase-3 and Caspase-8), autophagy-related proteins (Beclin-1, p62, Atg5 and Atg12) and the phosphorylation levels of ERK and Akt in FRO cells were measured by Western blot. The results showed that baicalein reduced the cell viability and cell colony numbers of FRO cells in a dose- and time-dependent manner. Baicalein also induced cell apoptosis and arrested the cell cycles of FRO cells. Baicalein decreased the ratio of Bcl-2/Bax but increased the expression of Caspase-3 and Caspase-8. Furthermore, baicalein induced autophagy in FRO cells. It significantly increased the expression of Beclin-1, Atg5, p62 and Atg12. Baicalein significantly decreased the ratios of p-ERK/ERK and p-Akt/Akt, indicating that it suppressed the ERK and PI3K/Akt pathways. In conclusion, baicalein could suppress the growth of undifferentiated thyroid cancer cells by inducing apoptosis and autophagy. The inhibition of the ERK and PI3K/Akt pathways may be involved in the mechanism.

Keywords: Baicalein; apoptosis; autophagy; undifferentiated thyroid cancer.