Differential sensitivity of colorectal cancer cell lines to artesunate is associated with expression of beta-catenin and E-cadherin.
Artesunate, a remarkable antimalarial agent, also reveals profound cytotoxic activity. In the present investigation, we compared the anticancer effects of artesunate on three colorectal cancer cell lines and analyzed the relationship between drug sensitivity and malignant phenotype of the tumor cells. The findings are as follows: poorly-differentiated was colorectal cancer cell line CLY showing nuclear beta-catenin accumulation and loss of E-cadherin; moderately-differentiated were Lovo cells with cytoplasmic distribution of the two proteins; and well-differentiated were HT-29 cells with membranous localization of them. Also, both in vitro and in vivo, poorly- or moderately-differentiated CLY and Lovo were more susceptible to artesunate treatment than well-differentiated HT-29. Furthermore, the sensitive response of CLY and Lovo to artesunate was associated with membranous translocation of beta-catenin and increased expression of E-cadherin, which indicated the inhibition of hyperactive Wnt signaling pathway and the reversion of the epithelial to mesenchymal transition, respectively. Due to the vital roles of Wnt pathway and the epithelial to mesenchymal transition in tumor differentiation, we thought artesunate could promote the re-differentiation and apoptosis of colorectal cancer cells by inhibition of hyperactive Wnt pathway and reversion of the epithelial to mesenchymal transition.
Li
Lin-Na
LN
Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, China.
Zhang
Hua-Dong
HD
Yuan
Shou-Jun
SJ
Yang
De-Xuan
DX
Wang
Lin
L
Sun
Zhi-Xian
ZX
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents; D017209:Apoptosis / Q000187:drug effects; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis*; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis; D013347:Subcellular Fractions / Q000187:drug effects; D051176:beta Catenin / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D037621:Artemisinins; D015820:Cadherins; D009363:Neoplasm Proteins; D051176:beta Catenin; D000077332:Artesunate