Carbon ion beam combined with cisplatin effectively disrupts triple negative breast cancer stem-like cells in vitro.

Abstract

AIMS:

Although a relatively small proportion of all breast cancer (BC), triple negative (TN) BC is responsible for a relatively large proportion of BC deaths because of its worse clinical outcome. To investigate whether a carbon ion beam alone or in combination with cisplatin (CDDP) has a beneficial effect compared to X-rays, we target triple negative (TN) breast cancer stem-like cells (CSCs).

METHODS:

Human breast CSCs sorted from MDA-MB-231 and MDA-MB-453 cells were treated with a carbon ion beam or X-ray irradiation alone or in combination with CDDP, and then colony, spheroid and tumor formation assays, RT-PCR Array analysis, and immunofluorescence γH2AX foci assay were performed.

RESULTS:

The colony, spheroid formation, and tumorigenicity assays confirmed that CD44+/CD24- and ESA+/CD24- cells have CSC properties in MDA-MB-231 and MDA-MB-453 cells, respectively. The proportion of CSCs was more enriched after CDDP combination with either X-ray or carbon ion beam, however carbon ion beam combined with CDDP significantly suppressed colony and spheroid formation and more significantly inhibited cell cycle progression (sub-G1 arrest) compared to X-ray combined with CDDP or carbon ion beam alone. RT-PCR Array analysis showed that carbon ion beam combined with CDDP significantly induced apoptosis-related Cytochrome c, almost completely eliminated expression of the CSC markers CD44 and ESA, and significantly inhibited angiogenesis, and metastasis-related HIF1α and CD26 compared to carbon ion beam alone, X-ray alone, or X-ray combined with CDDP. The immunofluorescence assay showed that not only the number but also the size of γH2AX foci in CSCs were larger 24 h after carbon ion beam combined with CDDP compared to those of X-ray alone and X-ray combined with CDDP.

CONCLUSIONS:

Carbon ion beam combined with CDDP has superior potential to kill TN breast CSCs with irreparable severe DNA damage and enhanced apoptosis.

• Authors: Sei Sai, Guillaume Vares, Eun Ho Kim, Kumiko Karasawa, Bing Wang, Mitsuru Nenoi, Yoshiya Horimoto, Mitsuhiro Hayashi
• Journal: Molecular cancer (Mol Cancer) Vol. 14 Pg. 166 (Sep 04 2015) ISSN: 1476-4598 [Electronic] England
• PMID: 26338199 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neoplasm Proteins
• Cisplatin

Topics

• Apoptosis (drug effects, radiation effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects, radiation effects)
• Cisplatin (administration & dosage)
• Combined Modality Therapy
• DNA Damage (drug effects, radiation effects)
• Female
• Gene Expression Regulation, Neoplastic (drug effects, radiation effects)
• Heavy Ion Radiotherapy
• Humans
• Neoplasm Proteins (biosynthesis)
• Neoplastic Stem Cells (drug effects, radiation effects)
• Triple Negative Breast Neoplasms (drug therapy, pathology, radiotherapy)
• X-Rays