1. Academic Validation
  2. The antagonism between apigenin and protoapigenone to the PDK-1 target in Macrothelypteris torresiana

The antagonism between apigenin and protoapigenone to the PDK-1 target in Macrothelypteris torresiana

  • Fitoterapia. 2019 Apr;134:14-22. doi: 10.1016/j.fitote.2019.02.005.
Ziwei Liu 1 Shuang Cao 1 Can Jin 1 Yu He 1 Xiaoshun Zhou 2 Heng Zhang 3 Zhimei Liu 4
Affiliations

Affiliations

  • 1 School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Xiongchu Avenue, No. 693, Wuhan, China.
  • 2 Conform Pharm Engineering Center, Humanwell Healthcare (group) Co. Ltd, Gaoxing Avenue, Biolake park, Wuhan, China.
  • 3 School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Xiongchu Avenue, No. 693, Wuhan, China. Electronic address: zhzpthm@163.com.
  • 4 Conform Pharm Engineering Center, Humanwell Healthcare (group) Co. Ltd, Gaoxing Avenue, Biolake park, Wuhan, China. Electronic address: zmeileo@yeah.net.
Abstract

Apigenin and protoapigenone that both have the activities against various Cancer cell lines co-exist in Macrothelypteris torresiana, while the extracts of M. torresiana couldn't achieve the fine anti-tumor effects for the existence of potent anti-tumor compounds. This study disclosed an antagonism between the two compounds on the protein level to elucidate the paradox. First, the study established the fingerprint for M. torresiana extract. The following anti-proliferation assay verified that the antagonism occurs between protoapigenone and apigenin. And then Western blot and qt-PCR were applied to evaluate the expression and transcription level of the Akt phosphorylation related targets to validate the antagonism at the protein level. Moreover, CETSA further validated the binding of PDK-1 with apigenin and protoapigenone, as well as the antagonism between the two compounds. Finally, the compound-protein complexes predicted by SYBYL-X gave the visual results for the antagonism. The results demonstrated that: Due to the structural similarity and close binding coefficients to the identical targets, when the cells were treated with apigenin and protoapigenone simultaneously, the Akt phosphorylation inhibition induced by protoapigenone would attenuate significantly. The antagonism disclosed in this paper could be a new explanation for the unsatisfied efficacy of M. torresiana extract.

Keywords

Akt phosphorylation; Antagonism; Apigenin; Macrothelypteris torresiana; Protoapigenone.

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