Effects of potential calcium sensing receptor inducers on promoting chemosensitivity of human colon carcinoma cells.
We have previously reported that by inducing calcium sensing receptor (CaSR), calcitriol, the active form of vitamin D, promoted the sensitivity of the human colon carcinoma cells to anticancer drugs. In the current study we tested several other potential CaSR modulators, calcipotriol and the effective components of Chinese herbal medicine lentinan, for their functions in inducing CaSR expression in human colon carcinoma cell line CBS, Moser, Fet, and SW480 cells and subsequently promoting sensitivity of the cells to anticancer drugs. Calcipotriol and lentinan suppressed invasion of the colon carcinoma cells and enhanced the cytotoxicity of anticancer regimen FOLFIRI to cells in culture or in anchorage-independent growth. In the mechanism study we found that calcipotriol and lentinan suppressed protein expression and gene transcriptional activities of survivin and thymidylate synthase, increased E-cadherin cell membrane localization and complex formation of E-cadherin and beta-catenin, and repressed TCF4 transcriptional activation. These effects were attenuated, however, in CaSR knocked-down cells, indicating that CaSR was required in the pathway. We concluded that calcipotriol and lentinan are efficient in promoting chemosensitivity in colon carcinoma cells. Since both compounds have much less side effects than calcitriol in clinic, they have greater potential to be applied as supplements of colon cancer therapy.
Wang
Xize
X
Department of General Surgery and Department of Experimental Medicine, Liaoning Northern Hospital, Shenyang 110016, Liaoning, P.R. China.
Chen
Wei
W
Singh
Navneet
N
Promkan
Multira
M
Liu
Guangming
G
D000230:Adenocarcinoma / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005472:Fluorouracil; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D047468:Immunoprecipitation; D007912:Lentinan / Q000494:pharmacology*; D002955:Leucovorin; D044169:Receptors, Calcium-Sensing / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D000970:Antineoplastic Agents; D044169:Receptors, Calcium-Sensing; C055085:calcipotriene; D007912:Lentinan; D002117:Calcitriol; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin