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Planta Med 2022; 88(13): 1141-1151
DOI: 10.1055/a-1728-5166
Biological and Pharmacological Activity
Original Papers

Natural Prenylated Xanthones as Potential Inhibitors of PI3k/Akt/mTOR Pathway in Triple Negative Breast Cancer Cells

Thi Thu Ha Nguyen   *
1   Institute of Chemistry, Vietnam Academy of Science and Technology, Hanoi, Vietnam
4   Graduate University of Sciences and Technology, Vietnam Academy of Science and Technology, Hanoi, Vietnam
,
Zhao Qu   *
2   Medical College of China Three Gorges University, Yichang, China
3   State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute, The Hong Kong Polytechnic University, Shenzhen, China
,
Van Tuyen Nguyen
1   Institute of Chemistry, Vietnam Academy of Science and Technology, Hanoi, Vietnam
4   Graduate University of Sciences and Technology, Vietnam Academy of Science and Technology, Hanoi, Vietnam
,
Thanh Tra Nguyen
1   Institute of Chemistry, Vietnam Academy of Science and Technology, Hanoi, Vietnam
4   Graduate University of Sciences and Technology, Vietnam Academy of Science and Technology, Hanoi, Vietnam
,
Thi Tu Anh Le
1   Institute of Chemistry, Vietnam Academy of Science and Technology, Hanoi, Vietnam
,
Sibao Chen
3   State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute, The Hong Kong Polytechnic University, Shenzhen, China
5   Research Center for Chinese Medicine Innovation, The Hong Kong Polytechnic University, Hong Kong, China
6   Department of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China
7   Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
,
Son The Ninh
1   Institute of Chemistry, Vietnam Academy of Science and Technology, Hanoi, Vietnam
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Abstract

Three prenylated xanthones, garcinone E (1), bannaxanthone D (2) and bannanxanthone E (3) were isolated from the leaves of Garcinia mckeaniana Graib. Their structures were elucidated by spectral methods and compared with literature data. To evaluate their anti-proliferative effects in tumor cells, firstly, cisplatin was used as a positive control and the effects of compound 1 – 3 were determined by performing MTT assay in MDA-MB-231, CNE-2 and A549 cancer cells. The results showed compound 1 – 3 exhibited stronger inhibitory effect than cisplatin in MDA-MB-231. Further effects of compound 1 – 3 in TNBC MDA-MB-231 and MDA-MB-468 cells were examined by performing cell cycle and apoptosis assays. The results indicated that compound 1 – 3 had ability to arrest cell cycle at G2/M phase and induce apoptosis. Furthermore, compound 2 significantly down-regulated PI3K, Akt and mTOR levels in both total proteins and phosphorylated form, which is its potential anti-cancer mechanism. These findings indicated that those prenylated xanthones might serve as promising leading compounds for the development of anticancer drug for TNBC.

Key words

Garcinia mckeaniana Graib - Prenylated xanthones - Anti-proliferative effect - Triple-negative breast cancer - PI3k/Akt/mTOR pathway

* Both authors contributed equally to work.




Publication History

Received: 15 August 2021

Accepted after revision: 28 December 2021

Accepted Manuscript online:
28 December 2021

Article published online:
24 February 2022

© 2022. Thieme. All rights reserved.

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