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A modified thymosin alpha 1 inhibits the growth of breast cancer both in vitro and in vivo: suppressment of cell proliferation, inducible cell apoptosis and enhancement of targeted anticancer effects

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Abstract

Thymosin alpha 1 (Tα1) is commonly used for treating several diseases; however its usage has been limited because of poor penetration of the target tissue, such as tumor cells. In the present study, Tα1-iRGD, a peptide by conjugating Tα1 with the iRGD fragment, was evaluated its performance in MCF-7 and MDA-MB-231 human breast cancer cells. Compared with the wild-type peptide, Tα1-iRGD was more selective in binding tumor cells in the cell attachment assay. Furthermore, the MTT assay confirmed that Tα1-iRGD proved more effective in significantly inhibiting the growth of MCF-7 cells in contrast to the general inhibition displayed by Tα1. Further, conjugation of Tα1 with iRGD preserved the immunomodulatory activity of the drug by increasing the proliferation of mouse spleen lymphocytes. Further, compared with Tα1 treatment, Tα1-iRGD treatment of MCF-7 cells considerably increased the number of cells undergoing apoptosis, resulting in a dose-dependent inhibition of cancer cell growth, which was associated with a much better effect on up-regulation of the expression of BCL2-associated X protein (Bax), caspase 9, etc. More importantly, treatment with Ta1-iRGD was more efficacious than treatment with Ta1 in vivo. This study highlights the importance of iRGD on enhancement of cell penetration and tumor accumulation. In summary, our findings demonstrate that the novel modified Tα1 developed in this study has the potential to be used for treating breast cancer.

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Acknowledgments

The authors would like to thank Dr. Jing Li for the discussions and helpful suggestions during this investigation. This work was supported by the National Natural Science Foundation of China (Grant No. 31300643) and a grant from the National High Technology Research and Development Program of China (863) (No. 2012AA020304) and the Fundamental Research Funds for the Central Universities (PT2014SK0062).

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  1. School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People’s Republic of China

    Xingzhen Lao, Bin Li, Meng Liu, Chen Shen, Tingting Yu, Xiangdong Gao & Heng Zheng

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  1. Xingzhen Lao
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Correspondence to Xiangdong Gao or Heng Zheng.

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Lao, X., Li, B., Liu, M. et al. A modified thymosin alpha 1 inhibits the growth of breast cancer both in vitro and in vivo: suppressment of cell proliferation, inducible cell apoptosis and enhancement of targeted anticancer effects. Apoptosis 20, 1307–1320 (2015). https://doi.org/10.1007/s10495-015-1151-z

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