The combination effect of sodium butyrate and 5-Aza-2'-deoxycytidine on radiosensitivity in RKO colorectal cancer and MCF-7 breast cancer cell lines.
BACKGROUND
The overall level of chromatin compaction is an important mechanism of radiosensitivity, and modification of DNA methylation and histone deacetylation may increase radiosensitivity by altering chromatin compaction. In this study, we investigated the effect of a demethylating agent, a histone deacetylase(HDAC) inhibitor, and the two agents combined on radiosensitivity in human colon and breast cancer cell lines.


METHODS
In this study, we used RKO colorectal cancer cell line and MCF-7 breast cancer cell lines and normal colon cell lines. On each of the cell lines, we used three different agents: the HDAC inhibitor sodium butyrate(SB), the demethylating agent 5-Aza-2'-deoxycytidine(5-aza-DC), and radiation. We then estimated the percentage of the cell survival using the XTT method and experimented to determine if there was an augmentation in the therapeutic effect by using different combinations of the two or three of the treatment methods.


RESULTS
After treatment of each cell lines with 5-aza-DC, SB and 6 grays of radiation, we observed that the survival fraction was lower after the treatment with 5-aza-DC or SB than with radiation alone in RKO and MCF-7 cell lines(p < 0.001). The survival fraction was lowest when the two agents, 5-aza-DC and SB were combined with radiation in both RKO and MCF-cell lines.


CONCLUSIONS
In conclusion, 5-aza-DC and SB can enhance radiosensitivity in both MCF-7 and RKO cell lines. The combination effect of a demethylating agent and an HDAC inhibitor is more effective than that of single agent treatment in both breast and colon cancer cell lines.
Cho
Hang Joo
HJ
Department of Surgery, Uijongbu St Mary's Hospital, College of Medicine, The Catholic University of Korea, South Korea. surgeryman@catholic.ac.kr
Kim
Sin Young
SY
Kim
Kee Hwan
KH
Kang
Won Kyung
WK
Kim
Ji Il
JI
Oh
Seong Tack
ST
Kim
Jeong Soo
JS
An
Chang Hyeok
CH
D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001943:Breast Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D002087:Butyrates / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D019175:DNA Methylation; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D011829:Radiation Dosage; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D002087:Butyrates; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D011838:Radiation-Sensitizing Agents; D000077209:Decitabine; D001374:Azacitidine