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Ethoxy mansonone G as an anticancer agent in estrogen receptor-positive and endocrine-resistant breast cancer
Piriya Chonsut1, Panupong Mahalapbutr2, Nalinee Pradubyat1,3
1Overcoming Cancer Drug Resistance Research Unit, Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
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.
Insights
Ethoxy mansonone G (EMG), a potent derivative of mansonone G, demonstrates significant anticancer effects across various breast cancer subtypes. This compound shows promise as a novel therapeutic agent for breast cancer treatment.
Area of Science:
- Pharmacology
- Molecular Biology
- Oncology
Background:
- Mansonone G (MG) derivatives are being explored for their therapeutic potential.
- Ethoxy mansonone G (EMG) is a potent derivative of MG.
- Breast cancer remains a significant global health challenge, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the anticancer effects of ethoxy mansonone G (EMG) in breast cancer cells.
- To elucidate the underlying mechanisms of EMG's action.
- To assess the safety profile of EMG.
Main Methods:
- Cell proliferation, migration, invasion, and anchorage-independent growth were assessed using MTT, scratch, Matrigel invasion, and soft agar assays.
- Estrogen receptor (ER)-targeted and endocrine-resistant genes were analyzed via RT-PCR and Western blot.
- Virtual molecular docking was employed to predict ERα binding.
Main Results:
- EMG exhibited potent anticancer activity in ER-positive, endocrine-resistant, and ER-negative breast cancer cells.
- EMG inhibited estrogen-induced proliferation and ER-targeted gene expression, indicating anti-estrogenic properties.
- EMG demonstrated synergistic effects with tamoxifen in endocrine-resistant cells and reduced expression of genes involved in invasion and metastasis.
Conclusions:
- Ethoxy mansonone G possesses significant anticancer properties in breast cancer.
- EMG warrants further investigation as a potential therapeutic agent for breast cancer patients.
- EMG's ability to target ER-positive, resistant, and negative cells broadens its therapeutic applicability.
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