Diallyl disulfide enhances carbon ion beams-induced apoptotic cell death in cervical cancer cells through regulating Tap73/ΔNp73

Diallyl disulfide (DADS), extracted from crushed garlic by steam-distillation, has been reported to provide the anticancer activity in severalcancertypes. However,the effect of DADS on high-LET carbon beams - induced cell death remains unknown. Therefore, we used human cervical cancer cells to elucidate the molecular effects ofthis dallylsulfide. Radiotherapy remains the mainstay of treatment, especially in advanced cervical cancer and there is still space to improve the radiosensitivity to reduce radiation dosage. In this study, we found that radiation effects evoked by high-LET carbon beam was marked by inhibition of cell viability, cell cycle arrest, significant rise of apoptotic cells, regulation of transcription factor, such as p73, as well as alterations of crucial mediator of theapoptosispathway. We further demonstratedthat pretreatment of 10 mu M DADS in HeLa cells exposed to radiation resulted in decrease in cell viability and increased radiosensitivity. Additionally, cells pretreated with DADS obviously inhibited the radiation-induced G2/M phase arrest, but promoted radiation-induced apoptosis. Moreover, combination DADS and the radiation exacerbated the activation of apoptosis pathways through up-regulated ration of pro-apoptotic Tap73 to anti-apoptotic Np73, and its downstream proteins, such as FASLG, and APAF1. Taken together, these results suggest thatDADS is a potentialcandidate as radio sensitive agent for cervical cancer.