Ethoxy mansonone G as an anticancer agent in estrogen receptor-positive and endocrine-resistant breast cancer

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 estrogeninduced 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 ERa. 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.

Controlled masking and targeted release of redox-cycling ortho-quinones via a C–C bond-cleaving 1,6-elimination

“…One underused family of cytotoxic natural products is the ortho -quinones. Several low-molecular-weight compounds that contain an ortho -quinone group, such as β-lapachone 8 , tanshinones (I, IIA, IIB and crypto) 9 , mansonones A–G 10 , dunnione 11 , miltirone 12 , salvicine 13 and caryopteron A 14 , display wide antiproliferative effects in vitro. For example, β-lapachone ( 1 , Fig.…”

Mansonone G and its derivatives exhibit membrane permeabilizing activities against bacteria

“…With the lack of success of synthetic antibiotics being introduced to the clinic, in recent years, attention has been turned to natural compounds, of both plant and animal origins, as promising candidates [ 1 ]. Therefore, in the quest to find new antibacterial molecules, our study was focused on screening mansonone G, a compound having known to possess a number of medicinal properties [ 9 , 12 – 14 , 17 , 18 ], and its derivatives, hypothesizing the possibility of finding some molecules that are active against Gram-positive and even Gram-negative bacteria.…”

“…Compounds from this botanical source, including the 1,2-naphthoquinones—mansonones—were also found to possess antifungal, antioxidant and larvicidal properties [ 12 ]. Mansonone G, a naturally occurring o -naphthoquinone (5% of CH 2 Cl 2 extract), has been studied by many and found to show antifungal [ 13 ] and anticancer [ 9 , 14 , 15 ] properties. Furthermore, cytotoxicity tests of mansonone G in HCT-116, HepG2, MCF-7 and HeLa cell lines also provided promising results [ 16 ] highlighting its potency as a good candidate for further drug development.…”

Allyl ether of mansonone G as a potential anticancer agent for colorectal cancer

“…Allyl and phenyl ethers of MG have demonstrated antibacterial activity against Staphylococcus aureus 64 times higher than the parent MG compound 3 . In addition, recent studies have reported that ethoxy and butoxy MGs were more cytotoxic to non-small cell lung cancer and breast cancer cells than their parent compound 7 , 8 . Therefore, the present study assessed the cytotoxic activity of MG and its ether analogs on two human colorectal cancer cells lines, HCT-116 cells carrying p53 wild-type and HT-29 cells carrying p53 mutant.…”