Dimethoxy Curcumin Induces Apoptosis by Suppressing Survivin and Inhibits Invasion by Enhancing E-Cadherin in Colon Cancer Cells.
BACKGROUND Dimethoxy curcumin (DMC) is a kind of lipophilic analog of curcumin with great improvement in chemical and metabolic stability. DMC has been studied in breast and renal cancer, but no research in colon cancer has been found yet. MATERIAL AND METHODS Two colon cancer cells (HT-29 and SW480) and one normal human colon mucosal epithelial cell (NCM460) were used in this study. We studied the effect of DMC on the proliferation in vitro and in vivo. Transwell migration assay was used to estimate the inhibition of DMC on invasion. Moreover, the expressions of PARP, caspase-3, survivin and E-cadherin were detected to uncover the related signaling pathways by western blotting assay both in vitro and in vivo. RESULTS DMC significantly inhibited the growth of colon cancer cells in dose-dependent manner; IC50 for DMC was calculated to be 43.4, 28.2 and 454.8µM on HT-29, SW480 and NCM460. DMC significantly increased the apoptosis in both HT-29 (p=0.0051) and SW480 (p=0.0013) cells in vitro, and significantly suppressed the growth of both cell lines in vivo. Moreover, DMC reduced the number of migrated cells in both HT-29 (p=0.007) and SW480 (p=0.004) cells. By western blotting analysis, the cleavage of pro-caspases-3 and PARP were clearly induced by DMC to their active form, while the expression of survivin was reduced and E-cadherin was enhanced in both cells in vitro and in vivo. CONCLUSIONS DMC may exert an effective anti-tumor effect in colon cancer cells by down-regulating survivin and upregulating E-cadherin.
Department of Colorectal Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland).
Dong
D
Chen
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu, China (mainland).
Fang
F
Dai
College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland).
Zhehang
Z
Chen
Department of Colorectal Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland).
Saisai
S
Wang
Department of Colorectal Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland).
Xiaobin
X
Cheng
Department of Colorectal Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland).
Qinsong
Q
Sheng
Department of Colorectal Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland).
Jianjiang
J
Lin
Department of Colorectal Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland).
Wenbin
W
Chen
D000818:Animals; D015703:Antigens, CD; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015820:Cadherins / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D000077022:Survivin; D023041:Xenograft Model Antitumor Assays
D015703:Antigens, CD; D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; C513384:CDH1 protein, human; D015820:Cadherins; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; C521105:dimethoxycurcumin; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D003474:Curcumin