butyricicoccus pullicaecorum

Butyrate supplementation regulates expression of chromosome segregation 1‑like protein to reverse the genetic distortion caused by p53 mutations in colorectal cancer

/ CY Liu / 發表迴響

Chun-Chao Chang 1, Wei-Yu Kao 1, Chih-Yi Liu 2, Hui-Hsien Su 1, Yu-An Kan 1, Pao-Ying Lin 1, Wei-Chi Ku 3, Kang-Wei Chang 4, Ruey-Neng Yang 3, Chi-Jung Huang 5

Affiliations
  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 11031, Taiwan, R.O.C.
  2. Department of Pathology, Sijhih Cathay General Hospital, New Taipei 22174, Taiwan, R.O.C.
  3. School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C.
  4. Neuroscience Research Center, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.
  5. Department of Medical Research, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C.

ABSTRACT

The chromosome segregation 1‑like (CSE1L) protein, which regulates cellular mitosis and apoptosis, was previously found to be overexpressed in colorectal cancer (CRC) cells harboring mutations. Therefore, regulating CSE1L expression may confer chemotherapeutic effects against CRC. The gut microflora can regulate gene expression in colonic cells. In particular, metabolites produced by the gut microflora, including the short‑chain fatty acid butyrate, have been shown to reduce CRC risk. Butyrates may exert antioncogenic potential in CRC cells by modulating p53 expression. The present study evaluated the association between CSE1L expression and butyrate treatment from two non‑transformed colon cell lines (CCD‑18Co and FHC) and six CRC cell lines (LS 174T, HCT116 p53+/+, HCT116 p53‑/‑, Caco‑2, SW480 and SW620). Lentiviral knockdown of CSE1L and p53, reverse transcription‑quantitative PCR (CSE1L, c‑Myc and p53), western blotting [CSE1L, p53, cyclin (CCN) A2, CCNB2 and CCND1], wound healing assay (cell migration), flow cytometry (cell cycle analysis) and immunofluorescence staining (CSE1L and tubulin) were adopted to verify the effects of butyrate on CSE1L‑expressing CRC cells. The butyrate‑producing gut bacteria Butyricicoccus pullicaecorum was administered to mice with 1,2‑dimethylhydrazine‑induced colon tumors before the measurement of CSE1L expression. The effects of B. pullicaecorum on CSE1L expression were then assessed by immunohistochemical staining for CSE1L and p53 in tissues from CRC‑bearing mice. Non‑cancerous colon cells with the R273H p53 mutation or CRC cells haboring p53 mutations were found to exhibit significantly higher CSE1L expression levels. CSE1L knockdown in HCT116 p53‑/‑ cells resulted in G1‑and G2/M‑phase cell cycle arrest. Furthermore, in HCT116 p53‑/‑ cells, CSE1L expression was already high at interphase, increased at prophase, peaked during metaphase before declining at cytokinesis but remained relatively high compared with that in HCT116 expressing wild‑type p53. Significantly decreased expression levels of CSE1L were also observed in HCT116 p53‑/‑ cells that were treated with butyrate for 24 h. In addition, the migration of HCT116 p53‑/‑ cells was significantly decreased after CSE1L knockdown or butyrate treatment. Tumors with more intense nuclear p53 staining and weaker CSE1L staining were found in mice bearing DMH/DSS‑induced CRC that were administered with B. pullicaecorum. Taken together, the results indicated that butyrate can impair CSE1L‑induced tumorigenic potential. In conclusion, butyrate‑producing microbes, such as B. pullicaecorum, may reverse the genetic distortion caused by p53 mutations in CRC by regulating CSE1L expression levels.

Keywords: butyricicoccus pullicaecorum; chromosome segregation 1‑like; colorectal cancer; p53 tumor suppressor; short‑chain fatty acid.

>Int J Oncol. 2022 Jun;60(6):64. doi: 10.3892/ijo.2022.5354. Epub 2022 Apr 13.

11. Butyrate supplementation regulates expression of chromosome segregation 1‑like protein (參考著作)下載

Supplementation of Probiotic Butyricicoccus pullicaecorum Mediates Anticancer Effect on Bladder Urothelial Cells by Regulating Butyrate-Responsive Molecular Signatures

/ CY Liu / 發表迴響

Yen-Chieh Wang 1 2, Wei-Chi Ku 2, Chih-Yi Liu 2 3, Yu-Che Cheng 2 4 5, Chih-Cheng Chien 2 6, Kang-Wei Chang 7 8, Chi-Jung Huang 4 9

Affiliations
  1. Department of Urology, Cathay General Hospital, Taipei 106438, Taiwan.
  2. School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 242062, Taiwan.
  3. Department of Pathology, Sijhih Cathay General Hospital, New Taipei 221037, Taiwan.
  4. Department of Medical Research, Cathay General Hospital, Taipei 106438, Taiwan.
  5. Department of Biomedical Sciences and Engineering, National Central University, Taoyuan 320317, Taiwan.
  6. Department of Anesthesiology, Cathay General Hospital, Taipei 106438, Taiwan.
  7. Taipei Neuroscience Institute, Taipei Medical University, Taipei 110301, Taiwan.
  8. Laboratory Animal Center, Taipei Medical University, Taipei 110301, Taiwan.
  9. Department of Biochemistry, National Defense Medical Center, Taipei 114201, Taiwan.

ABSTRACT

In bladder cancer, urothelial carcinoma is the most common histologic subtype, accounting for more than 90% of cases. Pathogenic effects due to the dysbiosis of gut microbiota are localized not only in the colon, but also in regulating bladder cancer distally. Butyrate, a short-chain fatty acid produced by gut microbial metabolism, is mainly studied in colon diseases. Therefore, the resolution of the anti-cancer effects of butyrate-producing microbes on bladder urothelial cells and knowledge of the butyrate-responsive molecules must have clinical significance. Here, we demonstrate a correlation between urothelial cancer of the bladder and Butyricicoccus pullicaecorum. This butyrate-producing microbe or their metabolite, butyrate, mediated anti-cancer effects on bladder urothelial cells by regulating cell cycle, cell growth, apoptosis, and gene expression. For example, a tumor suppressor against urothelial cancer of the bladder, bladder cancer-associated protein, was induced in butyrate-treated HT1376 cells, a human urinary bladder cancer cell line. In conclusion, urothelial cancer of the bladder is a significant health problem. To improve the health of bladder urothelial cells, supplementation of B. pullicaecorum may be necessary and can further regulate butyrate-responsive molecular signatures.

Keywords: Butyricicoccus pullicaecorum; apoptosis; bladder cancer-associated protein; butyrate; urothelial bladder cancer.

>Diagnostics (Basel). 2021 Dec 4;11(12):2270. doi: 10.3390/diagnostics11122270.

7. Supplementation of Probiotic Butyricicoccus pullicaecorum Mediates Anticancer Effect (參考著作)下載