Effects of the HDAC inhibitor CG2 in combination with irinotecan, 5-fluorouracil, or oxaliplatin on HCT116 colon cancer cells and xenografts.
Chemotherapies for colon cancer have recently advanced. However, there is still a need to develop agents and identify effective regimens for better treatments of colon cancer. Histone deacetylase inhibitors (HDACIs) have shown potential as anti-cancer agents. We investigated the anti-tumor effects of CG2 (an HDACI) in combination with irinotecan, 5-FU, or oxaliplatin. Combinations of CG2 with SN38 (the active form of irinotecan), 5FU, or oxaliplatin were more effective than the agents alone when used to inhibit the growth of HCT116 cells. The protein expressions of acetyl-H3, p21, caspase-3, -8, and -9, PARP, and XIAP were affected in a time- and dose-dependent manner in HCT116 cells treated with the CG2 alone or combined CG2 and SN-38. In HCT116 xenografts, the HDACI CG2 in combination with irinotecan dramatically inhibited tumor growth without showing additive toxicity. These data indicate that CG2 together with irinotecan is a promising combination novel treatment for colon cancer.
Institute for Innovate Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Young-Soon
YS
Na
Seung-Mi
SM
Kim
Kyung-Ah
KA
Jung
Soo-Jin
SJ
Yang
Yong Sang
YS
Hong
Min-Hee
MH
Ryu
Seonggu
S
Ro
Dong-Hyung
DH
Cho
Jin Cheon
JC
Kim
Dong-Hoon
DH
Jin
Jung Shin
JS
Lee
Tae Won
TW
Kim
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000008:administration & dosage*; D045325:HCT116 Cells; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D000077146:Irinotecan; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009281:Naphthalenes / Q000008:administration & dosage* / Q000494:pharmacology; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D009281:Naphthalenes; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin