PMID- 31707776
OWN - NLM
STAT- MEDLINE
DCOM- 20200420
LR  - 20240204
IS  - 0219-1032 (Electronic)
IS  - 1016-8478 (Print)
IS  - 1016-8478 (Linking)
VI  - 42
IP  - 11
DP  - 2019 Nov 30
TI  - Colorectal Cancer Therapy Using a Pediococcus pentosaceus SL4 Drug Delivery 
      System Secreting Lactic Acid Bacteria-Derived Protein p8.
PG  - 755-762
LID - 10.14348/molcells.2019.0064 [doi]
AB  - Despite decades of research into colorectal cancer (CRC), there is an ongoing 
      need for treatments that are more effective and safer than those currently 
      available. Lactic acid bacteria (LAB) show beneficial effects in the context of 
      several diseases, including CRC, and are generally regarded as safe. Here, we 
      isolated a Lactobacillus rhamnosus (LR)-derived therapeutic protein, p8, which 
      suppressed CRC proliferation. We found that p8 translocated specifically to the 
      cytosol of DLD-1 cells. Moreover, p8 down-regulated expression of Cyclin B1 and 
      Cdk1, both of which are required for cell cycle progression. We confirmed that p8 
      exerted strong anti-proliferative activity in a mouse CRC xenograft model. 
      Intraperitoneal injection of recombinant p8 (r-p8) led to a significant reduction 
      (up to 59%) in tumor mass when compared with controls. In recent years, bacterial 
      drug delivery systems (DDSs) have proven to be effective therapeutic agents for 
      acute colitis. Therefore, we aimed to use such systems, particularly LAB, to 
      generate the valuable therapeutic proteins to treat CRC. To this end, we 
      developed a gene expression cassette capable of inducing secretion of large 
      amounts of p8 protein from Pediococcus pentosaceus SL4 (PP). We then confirmed 
      that this protein (PP-p8) exerted anti-proliferative activity in a mouse CRC 
      xenograft model. Oral administration of PP-p8 DDS led to a marked reduction in 
      tumor mass (up to 64%) compared with controls. The PP-p8 DDS using LAB described 
      herein has advantages over other therapeutics; these advantages include improved 
      safety (the protein is a probiotic), cost-free purification, and specific 
      targeting of CRC cells.
FAU - An, Byung Chull
AU  - An BC
AD  - R&D Center, Cell Biotech, Co., Ltd., Gimpo 10003, Korea.
FAU - Ryu, Yongku
AU  - Ryu Y
AD  - R&D Center, Cell Biotech, Co., Ltd., Gimpo 10003, Korea.
FAU - Yoon, Yeo-Sang
AU  - Yoon YS
AD  - R&D Center, Cell Biotech, Co., Ltd., Gimpo 10003, Korea.
FAU - Choi, Oksik
AU  - Choi O
AD  - R&D Center, Cell Biotech, Co., Ltd., Gimpo 10003, Korea.
FAU - Park, Ho Jin
AU  - Park HJ
AD  - R&D Center, Cell Biotech, Co., Ltd., Gimpo 10003, Korea.
FAU - Kim, Tai Yeub
AU  - Kim TY
AD  - R&D Center, Cell Biotech, Co., Ltd., Gimpo 10003, Korea.
FAU - Kim, Song-In
AU  - Kim SI
AD  - R&D Center, Cell Biotech, Co., Ltd., Gimpo 10003, Korea.
FAU - Kim, Bong-Kyu
AU  - Kim BK
AD  - R&D Center, Cell Biotech, Co., Ltd., Gimpo 10003, Korea.
FAU - Chung, Myung Jun
AU  - Chung MJ
AD  - R&D Center, Cell Biotech, Co., Ltd., Gimpo 10003, Korea.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Cells
JT  - Molecules and cells
JID - 9610936
RN  - 0 (Bacterial Proteins)
RN  - 0 (Recombinant Proteins)
SB  - IM
MH  - Animals
MH  - Bacterial Proteins/*genetics/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects/genetics
MH  - Colorectal Neoplasms/*drug therapy/genetics/metabolism
MH  - Drug Delivery Systems/*methods
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - HT29 Cells
MH  - Humans
MH  - Injections, Intraperitoneal
MH  - Lacticaseibacillus rhamnosus/genetics/metabolism
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Pediococcus pentosaceus/*metabolism
MH  - Recombinant Proteins/*administration & dosage/metabolism
MH  - Xenograft Model Antitumor Assays/methods
PMC - PMC6883978
OTO - NOTNLM
OT  - Pediococcus pentosaceus SL4
OT  - anti-cancer activity
OT  - drug delivery system
OT  - probiotics
OT  - therapeutic protein
COIS- Disclosure The authors have no potential conflicts of interest to disclose.
EDAT- 2019/11/12 06:00
MHDA- 2020/04/21 06:00
PMCR- 2019/11/11
CRDT- 2019/11/12 06:00
PHST- 2019/04/05 00:00 [received]
PHST- 2019/07/29 00:00 [revised]
PHST- 2019/08/22 00:00 [accepted]
PHST- 2019/11/12 06:00 [pubmed]
PHST- 2020/04/21 06:00 [medline]
PHST- 2019/11/12 06:00 [entrez]
PHST- 2019/11/11 00:00 [pmc-release]
AID - S1016-8478(23)00447-8 [pii]
AID - molce-42-755 [pii]
AID - 10.14348/molcells.2019.0064 [doi]
PST - ppublish
SO  - Mol Cells. 2019 Nov 30;42(11):755-762. doi: 10.14348/molcells.2019.0064.