Development of novel application of 3,3'-diindolylmethane: sensitizing multidrug resistance human breast cancer cells to γ-irradiation.
BACKGROUND
Multidrug resistance (MDR) is known as a major obstacle to effective cancer therapy. The effects of irradiation on MDR in cancer cells had rarely been reported.


OBJECTIVE
The effect of 3,3'-diindolylmethane (DIM) sensitizing MDR human breast carcinoma to γ-irradiation was investigated.


METHODS
MCF-7/ADR cells were exposed to different concentrations of DIM (0-30 μM) for 48 or 2 h before IR (γ-Co60, 10 Gy, room temperature) then cultured for 48 h. Cell survival was determined by MTT assay. Intracellular reactive oxygen spices (ROS) induced by DIM (20 and 30 μM, 2 h before irradiation) was measured by flow cytometry. Propidium iodide staining assay was used for cell cycle distribution studies; cell apoptosis was measured by flow cytometry and confocal microscopy.


RESULTS
DIM (20 and 30 μM, 2 h before irradiation) sensitized MCF-7/ADR cells to IR with survival rates decreased from 100% to 79% and 63%, respectively. DIM combined with γ-radiation demonstrated that the activity of G2/M phase cell cycle arresting with percentages enhanced from 9% to 49% and 52%. DIM can increase intracellular ROS generation by 1.45- and 1.55-times compared to control group. Significantly enhanced radiation-induced apoptosis by DIM was also observed.


CONCLUSIONS
These data provide a rationale for the use of DIM as a promising radio-sensitizer to MDR cancer cells.
a Department of Blood Biopharmaceuticals and Viral Detection , Institute of Transfusion Medicine, The Academy of Military Medical Sciences , Beijing , P.R. China.
Wenjing
W
Wang
a Department of Blood Biopharmaceuticals and Viral Detection , Institute of Transfusion Medicine, The Academy of Military Medical Sciences , Beijing , P.R. China.
Maomin
M
Lv
a Department of Blood Biopharmaceuticals and Viral Detection , Institute of Transfusion Medicine, The Academy of Military Medical Sciences , Beijing , P.R. China.
Yanlin
Y
Wang
a Department of Blood Biopharmaceuticals and Viral Detection , Institute of Transfusion Medicine, The Academy of Military Medical Sciences , Beijing , P.R. China.
Jingang
J
Zhang
D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D005260:Female; D005720:Gamma Rays / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D007211:Indoles; D011838:Radiation-Sensitizing Agents; C016392:3,3'-diindolylmethane
Apoptosis; breast carcinoma; radio-sensitization