Soy isoflavones radiosensitize lung cancer while mitigating normal tissue injury

Abstract

Background We have demonstrated that soy isoflavones radiosensitize cancer cells. Prostate cancer patients receiving radiotherapy (RT) and soy tablets had reduced radiation toxicity to surrounding organs. We have now investigated the combination of soy with RT in lung cancer (NSCLC), for which RT is limited by radiation-induced pneumonitis. Methods Human A549 NSCLC cells were injected i. v. in nude mice to generate lung tumor nodules. Lung tumor-bearing mice were treated with left lung RT at 12 Gy and with oral soy treatments at 1mg/day for 30 days. Lung tissues were processed for histology. Results Compared to lung tumor nodules treated with soy isoflavones or radiation, lung tissues from mice treated with both modalities showed that soy isoflavones augmented radiation-induced destruction of A549 lung tumor nodules leading to small residual tumor nodules containing degenerating tumor cells with large vacuoles. Soy isoflavones decreased the hemorrhages, inflammation and fibrosis caused by radiation in lung tissue, suggesting protection of normal lung tissue. Conclusions Soy isoflavones augment destruction of A549 lung tumor nodules by radiation, and also mitigate vascular damage, inflammation and fibrosis caused by radiation injury to normal lung tissue. Soy could be used as a non-toxic complementary approach to improve RT in NSCLC.

Radioprotection of Lung Tissue by Soy Isoflavones

“…These survival pathways are further upregulated in response to radiation and thereby, are implicated in radioresistance of cancer. We have consistently shown that soy isoflavones inhibited radiation-induced upregulation of these survival pathways resulting in greater cancer destruction both in vitro and in vivo , using orthotopic models of lung carcinoma, renal cell carcinoma and prostate cancer (7-14). In particular, in lung cancer studies, we previously reported that soy isoflavones enhanced radiation-induced cell killing of human NSCLC cells in vitro by increasing DNA damage and inhibiting DNA repair in addition to inhibiting NF-κB and HIF-1α (12).…”

“…Initial studies suggested that soy inhibited the progression of radiation-induced inflammatory events in normal lung tissue. In an orthotopic murine model of lung cancer, soy isoflavones increased radiation-induced destruction of lung tumor nodules, but also mitigated the vascular damage, inflammation and fibrosis, caused by radiation injury to lung tissue (7). These studies suggested that soy isoflavones have the dual potential to enhance radiation damage in lung tumors and simultaneously protect normal lung from radiation injury.…”

Radioprotective effects of genistein on HL-7702 cells via the inhibition of apoptosis and DNA damage

“…Some studies have demonstrated that GEN can increase the survival rate of radiation-induced myelosuppressed mice [14][15][16]. Other data demonstrated that GEN also had radioprotective effects in nonhematopoietic tissues, including the lung, testis and intestine [17][18][19]. Son et al [20] found that GEN had a protective effect on intestinal damage induced by irradiation and inhibited tumor growth.…”

PIM1 kinase inhibitors induce radiosensitization in non-small cell lung cancer cells

“…Although such findings have contributed to limited information of the mechanism underlying cellular radioresistance, there are presently no molecular targeted therapies that can be effectively combined with radiation for treating lung cancer. Thus, the identification of biomarker(s) responsible for conferring radioresistance and modification of the irradiation response by radiosensitizers would greatly advance the discovery of drugs that enhance the sensitivity of NSCLC cells to radiation [8][9][10].…”