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Updated: Aug 19, 2026
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Selective cytotoxicity of ascochlorin in ER-negative human breast cancer cell lines
Koichi Sakaguchi1, Hiroo Nakajima, Naruhiko Mizuta
1Department of Endocrine, Breast Surgery, Kyoto Prefectural University of Medicine, Kawaramachi, Hirokoji, Kamikyo-ku, Kyoto 602-0841, Japan.
Abstract:
While agents targeting estrogen receptors are most effective in adjuvant therapy for human breast cancers expressing estrogen receptors after surgery, breast cancers lacking estrogen receptor are clinically serious, because they are highly malignant and exhibit resistance to the usual anti-cancer drugs, including estrogen receptor-antagonists and DNA breaking agents. Here, we found that MX-1, a human breast cancer cell line lacking estrogen receptors, exhibited higher AP-1 activity and expressed higher levels of c-Jun, c-Fos, and Fra-1 when compared with conventional estrogen receptor-positive human breast cancer cell lines. The prenylphenol antibiotic ascochlorin suppressed the AP-1 activity of MX-1 cells, and selectively killed MX-1 cells, partly due to induction of apoptosis. Our results suggest that AP-1 is an effective clinical target molecule for the treatment of estrogen receptor-negative human breast cancer.
Insights
Estrogen receptor-negative breast cancer is aggressive. Targeting AP-1 (activator protein-1) with ascochlorin shows promise for treating these difficult-to-treat cancers by inducing cell death.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Estrogen receptor (ER)-positive breast cancers respond well to targeted therapies.
- ER-negative breast cancers are aggressive, malignant, and resistant to conventional treatments like ER antagonists and DNA-damaging agents.
Purpose of the Study:
- To investigate potential therapeutic targets for ER-negative breast cancer.
- To explore the role of AP-1 (activator protein-1) activity in ER-negative breast cancer.
- To evaluate the efficacy of the prenylphenol antibiotic ascochlorin against ER-negative breast cancer cells.
Main Methods:
- Comparison of AP-1 activity and related protein expression (c-Jun, c-Fos, Fra-1) between ER-negative (MX-1) and ER-positive breast cancer cell lines.
- Treatment of MX-1 cells with ascochlorin.
- Assessment of AP-1 activity suppression and apoptosis induction in response to ascochlorin.
Main Results:
- ER-negative MX-1 cells exhibited higher AP-1 activity and elevated levels of c-Jun, c-Fos, and Fra-1 compared to ER-positive cell lines.
- Ascochlorin effectively suppressed AP-1 activity in MX-1 cells.
- Ascochlorin selectively induced apoptosis and inhibited the proliferation of MX-1 cells.
Conclusions:
- AP-1 is upregulated in ER-negative breast cancer and represents a potential therapeutic target.
- Ascochlorin demonstrates selective efficacy against ER-negative breast cancer by targeting AP-1 and inducing apoptosis.
- These findings suggest a novel therapeutic strategy for managing ER-negative breast cancer.
