title: Lactate calcium salt affects the viability of colorectal cancer cells via betaine homeostasis.
abstract: OBJECTIVE
  Betaine plays an important role in cellular homeostasis. However, the physiological roles of betaine-γ-aminobutyric acid (GABA) transporter (BGT-1) are still being disputed in cancer. In this study, we tried to find the possibility of the antitumor effect on colorectal cancer (CRC) cell via lactate calcium salt (CaLa)-induced BGT-1 downregulation.
  
  
  METHODS
  The CRC cell viability and clonogenic assay was performed using different doses of BGT-1 inhibitor. The expression level of BGT-1 was measured following the treatment of 2.5mM CaLa. Betaine was treated to confirm the resistance of the antitumor activity by CaLa. Tumor growth was also measured using a xenograft animal model.
  
  
  RESULTS
  Long-term exposure of 2.5mM CaLa clearly decreased the expression of BGT-1 in the CRC cells. As a result of the downregulation of BGT-1 expression, the clonogenic ability of CRC cells was also decreased in the 2.5mM CaLa-treated group. Reversely, the number of colonies and cell viability was increased by combination treatment with betaine and 2.5mM CaLa, as compared with a single treatment of 2.5mM CaLa. Tumor growth was significantly inhibited in the xenograft model depending on BGT-1 downregulation by 2.5mM CaLa treatment.
  
  
  CONCLUSIONS
  These results support the idea that long-lasting calcium supplementation via CaLa contributes to disruption of betaine homeostasis in the CRC cells 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.affiliation: Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, Republic of Korea.
authors.forename: Yeong-Su
authors.initials: YS
authors.lastname: Jang
authors.affiliation: Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, Republic of Korea.
authors.forename: Young-Kwon
authors.initials: YK
authors.lastname: Jo
authors.affiliation: Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, Republic of Korea.
authors.forename: Jae Jun
authors.initials: JJ
authors.lastname: Sim
authors.affiliation: Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, Republic of Korea.
authors.forename: Eunhee
authors.initials: E
authors.lastname: Ji
authors.affiliation: Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, Republic of Korea. Electronic address: alvirus@naver.com.
authors.forename: Keun-Yeong
authors.initials: KY
authors.lastname: Jeong
authors.affiliation: Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, Republic of Korea. Electronic address: hwanmook@gachon.ac.kr.
authors.forename: Hwan Mook
authors.initials: HM
authors.lastname: Kim
mesh_terms: D000818:Animals; D001622:Betaine / Q000378:metabolism*; D017610:Calcium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D050485:GABA Plasma Membrane Transport Proteins; D006706:Homeostasis; D006801:Humans; D007773:Lactates / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays
chemical_list: D017610:Calcium Compounds; D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D007773:Lactates; C072207:betaine plasma membrane transport proteins; C110051:calcium lactate; D001622:Betaine
keywords: Antitumor effect; BGT-1; Betaine; Colorectal cancer cell; Lactate calcium salt