Inorganic polyphosphate enhances radio-sensitivity in a human non-small cell lung cancer cell line, H1299.

Abstract

Inorganic polyphosphate is a linear polymer containing tens to hundreds of orthophosphate residues linked by high-energy phosphoanhydride bonds. Polyphosphate has been recognized as a potent anti-metastasis reagent. However, the molecular mechanism underlying polyphosphate action on cancer cells is poorly understood. In this study, we investigated the involvement of polyphosphate in radio-sensitivity using a human non-small cell lung cancer cell line, H1299. We found that polyphosphate treatment decreases cellular adenosine triphosphate levels, suggesting a disruption of energy metabolism. We also found that the induction of DNA double-strand breaks was enhanced in polyphosphate-treated cells after X-ray irradiation and colony formation assay revealed that cell survival decreased compared with that of the control groups. These findings suggest that polyphosphate is a promising radio-sensitizer for cancer cells. Therefore, we hypothesized that polyphosphate treatment disrupts adenosine triphosphate-mediated energy transfer for cellular survival and DNA repair, thereby reducing the cellular capability to resist X-ray irradiation.

• Authors: Kaori Tsutsumi, Yusuke Matsuya, Tomoki Sugahara, Manami Tamura, Satoshi Sawada, Sagiri Fukura, Hisashi Nakano, Hiroyuki Date
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 39 Issue 6 Pg. 1010428317705033 (Jun 2017) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 28651489 (Publication Type: Journal Article)

Chemical References

• Inorganic Chemicals
• Polyphosphates
• Radiation-Sensitizing Agents
• Adenosine Triphosphate

Topics

• Adenosine Triphosphate (metabolism)
• Carcinoma, Non-Small-Cell Lung (drug therapy, metabolism, pathology, radiotherapy)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Combined Modality Therapy
• DNA Breaks, Double-Stranded (drug effects)
• Energy Metabolism (drug effects)
• Humans
• Inorganic Chemicals (administration & dosage)
• Neoplasm Metastasis (drug therapy, pathology, radiotherapy)
• Polyphosphates (administration & dosage)
• Radiation Tolerance (drug effects)
• Radiation-Sensitizing Agents (administration & dosage)
• X-Rays