2. Academic Validation
  3. CT1-3, a novel magnolol-sulforaphane hybrid suppresses tumorigenesis through inducing mitochondria-mediated apoptosis and inhibiting epithelial mesenchymal transition

CT1-3, a novel magnolol-sulforaphane hybrid suppresses tumorigenesis through inducing mitochondria-mediated apoptosis and inhibiting epithelial mesenchymal transition

  • Eur J Med Chem. 2020 Aug 1;199:112441. doi: 10.1016/j.ejmech.2020.112441.
Cheng Tao 1,  Jian Chen 1,  Xiaofei Huang 2,  Zide Chen 3,  Xinping Li 4,  Yinghong Li 4,  Youqin Xu 5,  Min Ma 6,  Zhengzhi Wu 7
Affiliations

Affiliations

  • 1 Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China; Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, China; Shenzhen Institute of Geriatrics, Shenzhen, 518020, China; School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
  • 2 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 Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, China; Shenzhen Institute of Geriatrics, Shenzhen, 518020, China.
  • 5 School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • 6 College of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China; Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China.
  • 7 Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, 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: 32416457 DOI: 10.1016/j.ejmech.2020.112441
Abstract

Chemotherapy is recognized as one of the indispensable treatment for solid tumors. However, the emergent drug resistance and undesirable side effects have become a substantial challenge and the bottleneck of Cancer chemotherapy. Magnolol (MAG) is a natural polyphenol with various bioactivities. Sulforaphane (SFN) is identified as one of the most effective naturally occurring Anticancer agents. In this study, we successfully synthesized the magnolol-sulforaphane (MAG-SFN) hybrid CT1-3, showcasing more efficient Anticancer activity than its lead compounds MAG and SFN with IC50 values ranging from 5.10 to 14.06 μM in multiple Cancer cells. We also demonstrated that CT1-3 elicited a strong antitumor effect in vivo but has no hepatic and renal toxicity. Furthermore, we found out CT1-3 treatment resulted in reduction of Bcl-2 and XIAP levels, in addition to increase of phospho-JNK and Bax levels, leading to mitochondria-mediated Apoptosis in human Cancer cells. Moreover, we revealed that CT1-3 could reduce the capacity of migration and invasion of human Cancer cells via regulating the E-cadherin/Snail axis. Taken together, we provided strong evidences that the first example of MAG-SFN hybrid CT1-3 is a promising Anticancer drug candidate without apparent adverse effects, which suppresses tumorigenesis partly through inducing mitochondria-mediated Apoptosis and inhibiting epithelial mesenchymal transition (EMT).

Keywords

Apoptosis; Hybrid; Magnolol; Mitochondria; Sulforaphane.

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