Mucin Binding Protein of Lactobacillus casei Inhibits HT-29 Colorectal Cancer Cell Proliferation

Abstract

Many Lactobacillus casei strains are reported to exhibit anti-proliferative effects on colorectal cancer cells; however, the mechanism remains largely unknown. While there has been considerable interest in bacterial small metabolites such as short chain fatty acids, prior reports suggested that larger-sized molecules mediate the anti-proliferative effect of L. casei. Here, other possible ways of communication between gut bacteria and its host are investigated. LevH1 is a protein displayed on the surface of L. casei, and its mucin binding domain is highly conserved. Based on previous reports that the cell-free supernatant fractions decreased colorectal cell proliferation, we cloned the mucin binding domain of the LevH1 protein, expressed and purified this mucin binding protein (MucBP). It has a molecular weight of 10 kDa, is encoded by a 250 bp gene, and is composed primarily of a β-strand, β-turns, and random coils. The amino acid sequence is conserved while the 36th amino acid residue is arginine in L. casei CAUH35 and serine in L. casei IAM1045, LOCK919, 12A, and Zhang. MucBP36R exhibited dose-dependent anti-proliferative effects against HT-29 cells while a mutation of 36S abolished this activity. Predicted structures suggest that this mutation slightly altered the protein structure, thus possibly affecting subsequent communication with HT-29 cells. Our study identified a novel mode of communication between gut bacteria and their host.

The Crucial Roles of Diet, Microbiota, and Postbiotics in Colorectal Cancer

“… [ 110 ] Mucin binding protein-> Lactobacillus casei HT-29 • Anti-proliferative effects. [ 111 ] Cell wall – cytoplasmic extract, and nisin - Lactococcus lactis SW480 • Reducing cyclin D1 expression. • Anti-proliferative effect.…”

“…It has been shown that mucin-binding protein obtained from Lactobacillus casei can inhibit proliferation in HT-29 cells [ 111 ]. It has been determined that cytoplasmic extract and cell wall of Lactococcus lactis , and nisin showed antiproliferative effects by reducing cyclin D1 expression in SW480 cells.…”

Probiotic-Derived Bioactive Compounds in Colorectal Cancer Treatment

“…Probiotic-derived ferrichrome acts as a tumor-suppressive molecule via the c-Jun N-terminal kinase (JNK) signaling pathway against cancerous IECs to a greater extent than conventional chemotherapeutic drugs, including cisplatin and 5-FU [223]. The probiotic-derived P8 protein was found to eliminate metastasis [224] and suppress CRC growth via the inhibition of the Wnt signaling pathway [225], whereas mucin binding protein (MucBP) exhibits dose-dependent antiproliferative effects against HT-29 cells [226]. ↓ cell proliferation, extrinsic and intrinsic apoptosis induction, ↑ FasR and TRAILR1 expression (m2163)/ ↑ FasR, TNFR1, and TRAILR1 (m2386) [221] Mixirins (Bacillus sp.…”

“…HT-29 dose-dependent antiproliferative effect [226] Probiotic-derived P8 protein (Lactobacillus rhamnosus KCTC 12202BP) DLD-1…”