2. Academic Validation
  3. Iridoids from Valeriana jatamansi induce autophagy-associated cell death via the PDK1/Akt/mTOR pathway in HCT116 human colorectal carcinoma cells

Iridoids from Valeriana jatamansi induce autophagy-associated cell death via the PDK1/Akt/mTOR pathway in HCT116 human colorectal carcinoma cells

  • Bioorg Chem. 2019 Jun;87:136-141. doi: 10.1016/j.bioorg.2019.03.020.
Yu-Zhu Tan 1,  Cheng Peng 2,  Chang-Jiang Hu 3,  Hong-Xiang Li 4,  Wen-Bing Li 5,  Jun-Lin He 1,  Yu-Zhi Li 1,  Hai Zhang 1,  Ruo-Qi Zhang 1,  Li-Xia Wang 1,  Zhi-Xing Cao 6
Affiliations

Affiliations

  • 1 State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China.
  • 2 State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China. Electronic address: [email protected].
  • 3 School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China.
  • 4 Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China.
  • 5 Key Laboratory of Quality Control and Efficacy Evaluation of Traditional Chinese Medicine Formula Granules, Sichuan New Green Medicine Science and Technology Development Co. Ltd., Pengzhou 611930, PR China.
  • 6 State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China. Electronic address: [email protected].
PMID: 30884307 DOI: 10.1016/j.bioorg.2019.03.020
Abstract

Chlorovaltrates U-W (1-3), three previously undescribed Iridoids, together with four known analogues were isolated from the roots of Valeriana jatamansi. Their structures were elucidated by means of spectroscopic analyses (HRESIMS, NMR). The cytotoxicity of all isolates was evaluated. Compounds 5-7 exhibited selective cytotoxicity against HCT116 cells, with IC50 values of 9.3, 1.7 and 2.2 μM, respectively. The preliminary mechanistic study revealed that, the cytotoxicity effect of 6 was attributed to Akt/mTOR activation blockade via inhibition of PDK1 phosphorylation. Meanwhile, compound 6 could induce autophagosome formation in HCT116 cells via suppressing its downstream Akt/mTOR. These findings show that compound 6 could be of great importance to the development of anti-colon Cancer agents.

Keywords

Caprifoliaceae; Cytotoxicity; Iridoids; PDK1/Akt/mTOR; Valeriana jatamansi.

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