1. Academic Validation
  2. Daphnane Diterpenoids from Daphne genkwa Inhibit PI3K/Akt/mTOR Signaling and Induce Cell Cycle Arrest and Apoptosis in Human Colon Cancer Cells

Daphnane Diterpenoids from Daphne genkwa Inhibit PI3K/Akt/mTOR Signaling and Induce Cell Cycle Arrest and Apoptosis in Human Colon Cancer Cells

  • J Nat Prod. 2020 Apr 24;83(4):1238-1248. doi: 10.1021/acs.jnatprod.0c00003.
Rong-Rong Pan 1 Chun-Yan Zhang 1 Yuan Li 1 Bing-Bing Zhang 1 Liang Zhao 1 Ying Ye 1 Ya-Nan Song 1 Miao Zhang 1 Hong-Yun Tie 1 Hong Zhang 1 2 Jian-Yong Zhu 1
Affiliations

Affiliations

  • 1 Central Laboratory, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, People's Republic of China.
  • 2 Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People's Republic of China.
Abstract

Seven new daphnane-type Diterpenoids, daphgenkins A-G (1-7), and 15 known analogues (8-22) were isolated from the flower buds of Daphne genkwa. Their structures and absolute configurations were elucidated by spectroscopic data and calculated ECD analyses. The cytotoxicities of all daphnane-type Diterpenoids (1-22) obtained were evaluated against three human colon Cancer cell lines (SW620, RKO, and LoVo). Compounds 1, 12, and 13 exhibited cytotoxic effects against the SW620 and RKO cell lines, with IC50 values in the range of 3.0-9.7 μM. The most active new compound, 1, with an IC50 value of 3.0 μM against SW620 cells, was evaluated further for its underlying molecular mechanism. Compound 1 induced G0/G1 cell cycle arrest, leading to the induction of Apoptosis in SW620 cells. Also, it induced Cancer cell Apoptosis by an increased ratio of Bax/Bcl-2, activated cleaved Caspase-3 and caspase-9, and upregulated PARP. Finally, compound 1 significantly inhibited PI3K/Akt/mTOR signaling in SW620 cells. Together, the results suggest that compound 1 may be a suitable lead compound for further biological evaluation.

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