Kenta Kuramoto1, Masahiro Yamamoto1, Shuhei Suzuki1,2, Tomomi Sanomachi1,2, Keita Togashi1,3, Shizuka Seino1, Chifumi Kitanaka4,5, Masashi Okada4. 1. Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan. 2. Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Japan. 3. Department of Ophthalmology, Yamagata University School of Medicine, Yamagata, Japan. 4. Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan m-okada@med.id.yamagata-u.ac.jp ckitanak@med.id.yamagata-u.ac.jp. 5. Research Institute for Promotion of Medical Sciences, Yamagata University Faculty of Medicine, Yamagata, Japan.
Abstract
BACKGROUND/AIM: Cancer stem cells (CSCs) are associated with tumorigenesis, recurrence, and metastasis. Cell-cell communication via gap junctions (GJs) between metastatic cancer cells and astrocytes is necessary for brain metastasis. Agents targeting communication between CSCs and astrocytes are expected to suppress brain metastasis. MATERIALS AND METHODS: Using the A549 CSC, a cancer stem-like cell derived from A549, we examined the effect of AS602801, an anti-cancer stem cell agent whose safety has been confirmed in a phase 2 clinical trial, on GJ communication and connexin expression using a dye-transfer assay and immunoblot analysis, respectively. RESULTS: AS602801 specifically suppressed cell-cell communication in A549 CSCs without any suppression of GJ communication in astrocytes; it also decreased the expression of connexin 43, a constituent of GJs, in A549 CSCs. CONCLUSION: The anti-cancer stem cell agent, AS602801, is a potential drug candidate against brain metastasis. Copyright
BACKGROUND/AIM: Cancer stem cells (CSCs) are associated with tumorigenesis, recurrence, and metastasis. Cell-cell communication via gap junctions (GJs) between metastatic cancer cells and astrocytes is necessary for brain metastasis. Agents targeting communication between CSCs and astrocytes are expected to suppress brain metastasis. MATERIALS AND METHODS: Using the A549 CSC, a cancer stem-like cell derived from A549, we examined the effect of AS602801, an anti-cancer stem cell agent whose safety has been confirmed in a phase 2 clinical trial, on GJ communication and connexin expression using a dye-transfer assay and immunoblot analysis, respectively. RESULTS:AS602801 specifically suppressed cell-cell communication in A549 CSCs without any suppression of GJ communication in astrocytes; it also decreased the expression of connexin 43, a constituent of GJs, in A549 CSCs. CONCLUSION: The anti-cancer stem cell agent, AS602801, is a potential drug candidate against brain metastasis. Copyright
Authors: Soraya L Valles; Antonio Iradi; Martin Aldasoro; Jose M Vila; Constanza Aldasoro; Jack de la Torre; Juan Campos-Campos; Adrian Jorda Journal: Int J Med Sci Date: 2019-10-05 Impact factor: 3.738