CT2-3, a novel magnolol analogue suppresses NSCLC cells through triggering cell cycle arrest and apoptosis

  • Bioorg Med Chem. 2020 Mar 15;28(6):115352. doi: 10.1016/j.bmc.2020.115352.
Jian Chen  1 ,  Cheng Tao  1 ,  Xiaofei Huang  2 ,  Zide Chen  3 ,  Li Wang  4 ,  Xinping Li  5 ,  Min Ma  6 ,  Zhengzhi Wu  7
Affiliations
  • 1. Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou 510632, China; The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, China; Shenzhen Institute of Geriatrics, Shenzhen 518020, China.
  • 2. Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
  • 3. Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou 510632, China.
  • 4. Department of Cardiovascular Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, China.
  • 5. The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, China; Shenzhen Institute of Geriatrics, Shenzhen 518020, China.
  • 6. College of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China; The First Affiliated Hospital of Jinan University, Guangzhou 510630, China; Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou 510632, China. Electronic address: [email protected].
  • 7. The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, China; Shenzhen Institute of Geriatrics, Shenzhen 518020, China; The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 518033, China; Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou 510632, China. Electronic address: [email protected].
PMID: 32044229 DOI: 10.1016/j.bmc.2020.115352
Abstract

Magnolol, a major bioactive component found in Magnolia officinalis with anti-inflammation and anti-oxidation activities as well as minimized cytotoxic effects. Although magnolol has a wide range of clinical applications, the anti-tumor activity of magnolol is not efficient. Herein, we reported the synthesis and anti-cancer activities of three novel magnolol analogues CT2-1, CT2-2, CT2-3, among which CT2-3 revealed more efficient anti-non-small cell lung Cancer (NSCLC) activity than magnolol. Our data showed that CT2-3 could significantly inhibit the proliferation of human NSCLC cells in a dose-dependent manner. In addition, we revealed CT2-3 could induce cell cycle arrest through down-regulating mRNA expression of CDK4, CDK6 and cyclin D1. Moreover, we verified that CT2-3 could cause ROS generation, leading to Apoptosis of human NSCLC cells. Further more, we also provided strong evidences that CT2-3 down-regulates the expression of c-Myc and topoisomerases, and contributes to the Apoptosis of human NSCLC cells. Taken together, the current study is the first to report a promising new chemotherapeutic drug candidate CT2-3 that can efficiently eliminate human NSCLC cells through triggering cell cycle arrest as well as ROS-mediated and c-Myc/topoisomerases-mediated Apoptosis.

Keywords
Analogue; Apoptosis; Magnolol; NSCLC; ROS.
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