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 several cancer types. 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 of this diallyl sulfide. 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 the apoptosis pathway. We further demonstrated that pretreatment of 10 µM 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 ΔNp73, and its downstream proteins, such as FASLG, and APAF1. Taken together, these results suggest that DADS is a potential candidate as radio sensitive agent for cervical cancer.
a Department of Heavy Ion Radiation Medicine ; Institute of Modern Physics; Chinese Academy of Sciences ; Lanzhou , China.|b Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences ; Lanzhou , China.|c Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; Lanzhou , China.
Cuixia
C
Di
a Department of Heavy Ion Radiation Medicine ; Institute of Modern Physics; Chinese Academy of Sciences ; Lanzhou , China.|b Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences ; Lanzhou , China.|c Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; Lanzhou , China.
Chao
C
Sun
a Department of Heavy Ion Radiation Medicine ; Institute of Modern Physics; Chinese Academy of Sciences ; Lanzhou , China.|b Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences ; Lanzhou , China.|c Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; Lanzhou , China.
Hongyan
H
Li
a Department of Heavy Ion Radiation Medicine ; Institute of Modern Physics; Chinese Academy of Sciences ; Lanzhou , China.|b Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences ; Lanzhou , China.|c Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; Lanzhou , China.
Jing
J
Si
a Department of Heavy Ion Radiation Medicine ; Institute of Modern Physics; Chinese Academy of Sciences ; Lanzhou , China.|b Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences ; Lanzhou , China.|c Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; Lanzhou , China.
Hong
H
Zhang
a Department of Heavy Ion Radiation Medicine ; Institute of Modern Physics; Chinese Academy of Sciences ; Lanzhou , China.|b Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences ; Lanzhou , China.|c Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; Lanzhou , China.
Lu
L
Han
a Department of Heavy Ion Radiation Medicine ; Institute of Modern Physics; Chinese Academy of Sciences ; Lanzhou , China.|b Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences ; Lanzhou , China.|c Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; Lanzhou , China.
Qiuyue
Q
Zhao
a Department of Heavy Ion Radiation Medicine ; Institute of Modern Physics; Chinese Academy of Sciences ; Lanzhou , China.|b Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences ; Lanzhou , China.|c Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; Lanzhou , China.
Yang
Y
Liu
d College of Stomatology ; Lanzhou University ; Lanzhou , China.
Bin
B
Liu
a Department of Heavy Ion Radiation Medicine ; Institute of Modern Physics; Chinese Academy of Sciences ; Lanzhou , China.|b Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences ; Lanzhou , China.|c Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; Lanzhou , China.
Guoying
G
Miao
a Department of Heavy Ion Radiation Medicine ; Institute of Modern Physics; Chinese Academy of Sciences ; Lanzhou , China.|b Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences ; Lanzhou , China.|c Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; Lanzhou , China.
Lu
L
Gan
a Department of Heavy Ion Radiation Medicine ; Institute of Modern Physics; Chinese Academy of Sciences ; Lanzhou , China.|b Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences ; Lanzhou , China.|c Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province ; Lanzhou , China.
Yuanyuan
Y
Liu
D000498:Allyl Compounds / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000235:genetics*; D004220:Disulfides / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D006367:HeLa Cells; D063193:Heavy Ion Radiotherapy; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*
D000498:Allyl Compounds; D004268:DNA-Binding Proteins; D004220:Disulfides; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C000606369:delta Np73 protein, human; C028009:diallyl disulfide
Diallyl disulfide; Tap73; apoptosis; cervical carcinoma; high-LET carbon beam; radiosensitivity; ΔNp73