Differential effect of soy isoflavones in enhancing high intensity radiotherapy and protecting lung tissue in a pre-clinical model of lung carcinoma

• Published in: Radiotherapy and oncology 2013-10, Vol.109 (1), p.117-125
• Main Authors: Hillman, Gilda G, Singh-Gupta, Vinita, Hoogstra, David J, Abernathy, Lisa, Rakowski, Joseph, Yunker, Christopher K, Rothstein, Shoshana E, Sarkar, Fazlul H, Gadgeel, Shirish, Konski, Andre A, Lonardo, Fulvio, Joiner, Michael C
• Format: Article
• Language: English
• Subjects: Animals; Cell Line, Tumor; Cytokines - biosynthesis; Female; Glycine max - chemistry; Hematology, Oncology and Palliative Medicine; Humans; Isoflavones - pharmacology; Lung - radiation effects; Lung cancer; Lung Neoplasms - radiotherapy; Mice; Radiation; Radiation Pneumonitis - prevention & control; Radiation-Protective Agents - pharmacology; Radiation-Sensitizing Agents - pharmacology; Soy isoflavones
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/j.radonc.2013.08.015

Abstract Background Radiotherapy of locally-advanced non-small cell lung cancer is limited by radiation-induced pneumonitis and fibrosis. We have further investigated the role of soy isoflavones to improve the effect of a high intensity radiation and reduce lung damage in a pre-clinical lung tumor model. Methods Human A549 NSCLC cells were injected i.v. in nude mice to generate a large tumor burden in the lungs. Mice were treated with lung irradiation at 10 Gy and with oral soy. The therapy effect on the tumor cells and surrounding lung tissue was analyzed on lung sections stained with H&E, Ki-67 and Masson’s Trichrome. Pneumonitis and vascular damage were evaluated by measurements of alveolar septa and immunofluorescent staining of vessel walls. Results Combined soy and radiation caused a significantly stronger inhibition of tumor progression compared to each modality alone in contrast to large invasive tumor nodules seen in control mice. At the same time, soy reduced radiation injury in lung tissue by decreasing pneumonitis, fibrosis and protecting alveolar septa, bronchioles and vessels. Conclusions These studies demonstrate a differential effect of soy isoflavones on augmenting tumor destruction induced by radiation while radioprotecting the normal lung tissue and support using soy to alleviate radiotoxicity in lung cancer.