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

Jian Chen; Cheng Tao; Xiaofei Huang; Zide Chen; Li Wang; Xinping Li; Min Ma; Zhengzhi Wu

doi:10.1016/j.bmc.2020.115352

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. Epub 2020 Feb 3.

Authors

Jian Chen¹, Cheng Tao¹, Xiaofei Huang², Zide Chen³, Li Wang⁴, Xinping Li⁵, Min Ma⁶, Zhengzhi Wu⁷

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: tmamin@jnu.edu.cn.
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: szwzz001@email.szu.edu.cn.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents, Phytogenic / chemical synthesis
Antineoplastic Agents, Phytogenic / chemistry
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects*
Cell Cycle Checkpoints / drug effects
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Magnolia / chemistry
Molecular Structure
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

Antineoplastic Agents, Phytogenic