ONCOmmunity

Suppression of AKT Potentiates Synergistic Cytotoxicity of Apigenin with TRAIL in Anaplastic Thyroid Carcinoma Cells.

By: Si Hyoung Kim, Jun Goo Kang, Chul Sik Kim, Sung-Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, Seong Jin Lee

Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
2015-12-6; doi:

Abstract

Background

We studied the effect of apigenin in combination with tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on cell survival and the influence of AKT inhibition on the combined effect of apigenin with TRAIL in anaplastic thyroid carcinoma (ATC) cells.

Materials

The human 8505C and CAL62 ATC cell lines were used.

Results

Apigenin in combination with TRAIL, compared to apigenin alone, reduced cell viability and Bcl2 protein levels, elevated the percentage of dead cells, as well as the protein levels of cleaved PARP and phospho-ERK1/2. The protein levels of Bcl-xL, Bax, Bid, total ERK1/2, and total and phospho-AKT were unchanged. Administration of wortmannin further reduced cell viability, and elevated the percentage of dead cells, cytotoxic activity and cleaved PARP protein levels.

Conclusion

Apigenin synergizes with TRAIL through regulation of Bcl2 family proteins in inducing cytotoxicity, and suppression of AKT potentiates synergistic cytotoxicity of apigenin with TRAIL in ATC cells.