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

Thi Thu Ha Nguyen; Zhao Qu; Van Tuyen Nguyen; Thanh Tra Nguyen; Thi Tu Anh Le; Sibao Chen; Son The Ninh

doi:10.1055/a-1728-5166

Planta Medica, Inhaltsverzeichnis

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^*

¹Institute of Chemistry, Vietnam Academy of Science and Technology, Hanoi, Vietnam

⁴Graduate University of Sciences and Technology, Vietnam Academy of Science and Technology, Hanoi, Vietnam

,

Zhao Qu^*

²Medical College of China Three Gorges University, Yichang, China

³State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute, The Hong Kong Polytechnic University, Shenzhen, China

,

Van Tuyen Nguyen

¹Institute of Chemistry, Vietnam Academy of Science and Technology, Hanoi, Vietnam

⁴Graduate University of Sciences and Technology, Vietnam Academy of Science and Technology, Hanoi, Vietnam

,

Thanh Tra Nguyen

¹Institute of Chemistry, Vietnam Academy of Science and Technology, Hanoi, Vietnam

⁴Graduate University of Sciences and Technology, Vietnam Academy of Science and Technology, Hanoi, Vietnam

,

Thi Tu Anh Le

¹Institute of Chemistry, Vietnam Academy of Science and Technology, Hanoi, Vietnam

,

Sibao Chen

³State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute, The Hong Kong Polytechnic University, Shenzhen, China

⁵Research Center for Chinese Medicine Innovation, The Hong Kong Polytechnic University, Hong Kong, China

⁶Department of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China

⁷Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

,

Son The Ninh

¹Institute of Chemistry, Vietnam Academy of Science and Technology, Hanoi, Vietnam

› Institutsangaben

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

Volltext

Referenzen

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