title: Investigation of lactate calcium salt-induced β-catenin destabilization in colorectal cancer cells.
abstract: OBJECTIVE
  Calcium supplements appear to reduce the risk of developing colorectal cancer (CRC), and it is necessary to clarify the mechanisms by which they exert their effects. In the present study, we investigate the supplementation effect of calcium via lactate calcium salt (CaLa) on CRC cells, focusing on β-catenin destabilization.
  
  
  METHODS
  The clonogenic assay was performed using different doses of CaLa. The expression level of c-Myc and Cyclin D1 was measured in addition to the confirmation of β-catenin expression in the CRC cells. Glycogen synthase kinase (GSK)-3β expression was also confirmed in order to investigate the mechanism of β-catenin degradation. Tumorigenic ability was confirmed using a xenograft animal model.
  
  
  RESULTS
  The number of colonies was significantly decreased after 2.5mM CaLa treatment. CaLa-treated CRC cells showed a decrease in the β-catenin expression. The quantitative level of the β-catenin protein was significantly decreased in the CRC cell lysates, hence the expression level of c-Myc and cyclin D1 was significantly decreased following 2.5mM CaLa treatment. We also confirmed that an increased expression of GSK-3β by CaLa is a key pathway in β-catenin degradation. In the xenograft study, tumorigenicity was significantly inhibited to a maximum of 45% in the CaLa-treated group as compared with the control.
  
  
  CONCLUSIONS
  These results support the idea that calcium supplementation via CaLa contributes to β-catenin degradation and is hypothesized to reduce the risk of CRC. In addition, it indicates the possibility of CaLa being a potential incorporating agent with existing therapeutics against CRC.
authors: Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, Republic of Korea.
authors: Yeong-Su
authors: YS
authors: Jang
authors: Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, Republic of Korea.
authors: Jae Jun
authors: JJ
authors: Sim
authors: Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, Republic of Korea.
authors: Eunhee
authors: E
authors: Ji
authors: Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, Republic of Korea. Electronic address: alvirus@naver.com.
authors: Keun-Yeong
authors: KY
authors: Jeong
authors: Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, Republic of Korea. Electronic address: hwanmook@gachon.ac.kr.
authors: Hwan Mook
authors: HM
authors: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017610:Calcium Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007773:Lactates / Q000494:pharmacology / Q000627:therapeutic use*; D008807:Mice, Inbred BALB C; D059748:Proteolysis / Q000187:drug effects; D012007:Rectum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051176:beta Catenin / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D017610:Calcium Compounds; D007773:Lactates; D051176:beta Catenin; C110051:calcium lactate
keywords: Antitumor effect; Colorectal cancer; Lactate calcium salt; c-Myc; β-Catenin