The chemopreventive flavonoid apigenin confers radiosensitizing effect in human tumor cells grown as monolayers and spheroids.
Apigenin, a common dietary flavonoid present in many fruits and vegetables, is a nonmutagenic chemopreventive agent. In the present study, we investigated the effect of apigenin on the radiosensitivity of SQ-5 cells, which are derived from a human lung carcinoma. Actively growing cells were incubated for 16 h at 37 degrees C in medium containing 40 muM apigenin. The cells were then irradiated with X-rays and incubated with apigenin for a further 8 h. Radiosensitivity was assessed using a clonogenic assay. Apoptosis and necrosis were assessed using acridine orange/ethidium bromide double staining. Cells incubated with apigenin exhibited significantly greater radiosensitivity and apoptosis levels than cells not incubated with apigenin. Protein levels were measured by Western blotting. Incubation with apigenin increased protein expression of WAF1/p21 and decreased protein expression of Bcl-2. Furthermore, apigenin sensitized SQ-5 spheroids (cell aggregates growing in a three-dimensional structure that simulate the growth and microenvironmental conditions of in vivo tumors) to radiation. Thus, apigenin appears to be a promising radiosensitizing agent for use against human carcinomas.
Watanabe
Norihiro
N
Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, Ibaraki, Japan.
Hirayama
Ryoichi
R
Kubota
Nobuo
N
D016588:Anticarcinogenic Agents / Q000008:administration & dosage; D047310:Apigenin / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000187:drug effects*; D018874:Spheroids, Cellular / Q000473:pathology / Q000528:radiation effects
D016588:Anticarcinogenic Agents; D047310:Apigenin