2. Academic Validation
  3. CLE-10 from Carpesium abrotanoides L. Suppresses the Growth of Human Breast Cancer Cells (MDA-MB-231) In Vitro by Inducing Apoptosis and Pro-Death Autophagy Via the PI3K/Akt/mTOR Signaling Pathway

CLE-10 from Carpesium abrotanoides L. Suppresses the Growth of Human Breast Cancer Cells (MDA-MB-231) In Vitro by Inducing Apoptosis and Pro-Death Autophagy Via the PI3K/Akt/mTOR Signaling Pathway

  • Molecules. 2019 Mar 20;24(6):1091. doi: 10.3390/molecules24061091.
Li Tian 1,  Fan Cheng 2,  Lei Wang 3,  Wen Qin 4,  Kun Zou 5,  Jianfeng Chen 6
Affiliations

Affiliations

  • 1 Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang 443002, China. [email protected].
  • 2 Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang 443002, China. [email protected].
  • 3 Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang 443002, China. [email protected].
  • 4 Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang 443002, China. [email protected].
  • 5 Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang 443002, China. [email protected].
  • 6 Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang 443002, China. [email protected].
PMID: 30897708 DOI: 10.3390/molecules24061091
Abstract

Background: The antitumor activity of CLE-10 (4-epi-isoinuviscolide), a sesquiterpene lactone compound, isolated from Carpesium abrotanoides L. has rarely been reported. The aim of this study is to investigate the antitumor activity of CLE-10 and give a greater explanation of its underlying mechanisms.

Methods: The cytotoxicity of CLE-10 was evaluated using MTT assay. Autophagy was detected by the formation of mRFP-GFP-LC3 fluorescence puncta and observed using transmission electron microscopy, while flow cytometry was employed to detect Apoptosis. The protein expressions were detected through Western blotting.

Results: CLE-10 induced pro-death Autophagy and Apoptosis in MDA-MB-231 cells by increasing the protein expression of LC3-II, p-ULK1, Bax, and Bad, as well as downregulating p-PI3K, p-Akt, p-mTOR, p62, LC3-I, Bcl-2, and Bcl-xL. CLE-10 that was pretreated with 3-methyladenine (3-MA) or chloroquine (CQ) weakened the upregulation of the protein expression of p-ULK1, or the downregulation of p62, p-mTOR, and decreased the level of cytotoxicity against MDA-MB-231 cells. Meanwhile, rapamycin enhanced the effect of CLE-10 on the expression of autophagy-related protein and its cytotoxicity, with the IC50 value of CLE-10 decreasing from 4.07 µM to 2.38 µM.

Conclusion: CLE-10 induced pro-death Autophagy and Apoptosis in MDA-MB-231 cells by upregulating the protein expressions of LC3-II, p-ULK1, Bax, and Bad and downregulating p-PI3K, p-Akt, p-mTOR, p62, Bcl-2, and Bcl-xL.

Keywords

CLE-10; LC3; MDA-MB-231; PI3K/AKT/mTOR; apoptosis; autophagy.

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