Piriya Chonsut1, Panupong Mahalapbutr2, Nalinee Pradubyat1,3, Warinthorn Chavasiri4, Piyanuch Wonganan1, Wannarasmi Ketchart1. 1. Overcoming Cancer Drug Resistance Research Unit, Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 2. Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand. 3. Department of Pharmacology, College of Pharmacy, Rangsit University, Pathumthani, Thailand. 4. Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
Abstract
OBJECTIVES: To study anticancer effects, underlying mechanism and safety of ethoxy mansonone G (EMG) which is the potent derivative of mansonone G (MG) in breast cancer cells. METHODS: Anticancer, antimigration, anti-invasion effects and anchorage-independent growth were investigated by MTT, scratch, matrigel invasion and soft agar assays. Estrogen receptor (ER)-targeted genes and endocrine-resistant genes were assessed by RT-PCR and Western blot. KEY FINDINGS: Ethoxy mansonone G is the most potent MG derivative and has anticancer effects in ER-positive, endocrine-resistant and ER-negative breast cancer cells. Our results demonstrated that EMG can significantly inhibit estrogen-induced cell proliferation and the expression of ER-targeted genes in ER-positive breast cancer cells, suggesting the anti-estrogenic property of EMG which is consisting with the virtual molecular docking that EMG could possibly bind to the ERα. Moreover, EMG has synergistic effect with tamoxifen in endocrine-resistant cells. EMG also inhibited cell proliferation, invasion and anchorage-independent growth by reducing expression of genes involved in endocrine resistance and invasive factors during the metastatic process. CONCLUSION: Ethoxy mansonone G has an anticancer effect in breast cancer cells and is possible to use as a therapeutic agent in patients with breast cancer.
OBJECTIVES: To study anticancer effects, underlying mechanism and safety of ethoxy mansonone G (EMG) which is the potent derivative of mansonone G (MG) in breast cancer cells. METHODS: Anticancer, antimigration, anti-invasion effects and anchorage-independent growth were investigated by MTT, scratch, matrigel invasion and soft agar assays. Estrogen receptor (ER)-targeted genes and endocrine-resistant genes were assessed by RT-PCR and Western blot. KEY FINDINGS:Ethoxy mansonone G is the most potent MG derivative and has anticancer effects in ER-positive, endocrine-resistant and ER-negative breast cancer cells. Our results demonstrated that EMG can significantly inhibit estrogen-induced cell proliferation and the expression of ER-targeted genes in ER-positive breast cancer cells, suggesting the anti-estrogenic property of EMG which is consisting with the virtual molecular docking that EMG could possibly bind to the ERα. Moreover, EMG has synergistic effect with tamoxifen in endocrine-resistant cells. EMG also inhibited cell proliferation, invasion and anchorage-independent growth by reducing expression of genes involved in endocrine resistance and invasive factors during the metastatic process. CONCLUSION:Ethoxy mansonone G has an anticancer effect in breast cancer cells and is possible to use as a therapeutic agent in patients with breast cancer.
Authors: Claudio D Navo; Julie Becher; Enrique Gil de Montes; Ana Guerreiro; Lavinia Dunsmore; Emily Hoyt; Libby Brown; Viviane Zelenay; Sigitas Mikutis; Jonathan Cooper; Isaia Barbieri; Stefanie Lawrinowitz; Elise Siouve; Esther Martin; Pedro R Ruivo; Tiago Rodrigues; Filipa P da Cruz; Oliver Werz; George Vassiliou; Peter Ravn; Gonzalo Jiménez-Osés; Gonçalo J L Bernardes Journal: Nat Chem Date: 2022-06-27 Impact factor: 24.274