Int J Med Sci 2020; 17(11):1482-1490. doi:10.7150/ijms.46925

Research Paper

Arnicolide D Inhibits Triple Negative Breast Cancer Cell Proliferation by Suppression of Akt/mTOR and STAT3 Signaling Pathways

Zhao Qu1, Yushan Lin1, Daniel Kam-Wah Mok1,2, Qingya Bian3, William Chi-Shing Tai1,2✉, Sibao Chen1,2,3✉

1. State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute, The Hong Kong Polytechnic University, Shenzhen 518057, China.
2. Department of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong S.A.R., China.
3. Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.

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Citation:
Qu Z, Lin Y, Mok DKW, Bian Q, Tai WCS, Chen S. Arnicolide D Inhibits Triple Negative Breast Cancer Cell Proliferation by Suppression of Akt/mTOR and STAT3 Signaling Pathways. Int J Med Sci 2020; 17(11):1482-1490. doi:10.7150/ijms.46925. Available from https://www.medsci.org/v17p1482.htm

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Abstract

Triple-Negative Breast Cancer (TNBC) is a most dangerous breast cancer subtype. The naturally occurring sesquiterpene lactone, arnicolide D (AD), has proven effective against a variety of tumors, however, the inhibitory effects of AD against TNBC and the underlying mechanisms remain unclear. In the present study, two TNBC cell lines (MDA-MB-231 and MDA-MB-468) and an MDA-MB-231 xenograft mouse model were employed to investigate the anti-TNBC effects of AD in vitro and in vivo. Cell viability was assessed by MTT assay. Cell cycle arrest and apoptosis were analyzed by flow cytometry. Protein levels were determined by immunoblotting. In vitro studies demonstrated that AD significantly decreased cell viability, and induced G2/M cell cycle arrest and apoptosis. In vivo assays showed that oral administration of 25 or 50 mg/kg AD for 22 days led to a reduction of tumor weights by 24.7% or 41.0%, without appreciable side effects. Mechanistically, AD inhibited the activation of Akt/mTOR and STAT3 signaling pathways. Based on our findings, AD is a promising candidate for development as an adjunctive therapeutic drug for TNBC.

Keywords: Arnicolide D, Triple negative breast cancer, Akt/mTOR, STAT3