Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells
- 2016-02-05
- PLOS ONE 11(2)
- A. Tiptiri-Kourpeti
- K. Spyridopoulou
- Valentina Santarmaki
- Georgios Aindelis
- Evgenia Tompoulidou
- E. Lamprianidou
- G. Saxami
- P. Ypsilantis
- E. Lampri
- C. Simopoulos
- I. Kotsianidis
- A. Galanis
- Y. Kourkoutas
- D. Dimitrellou
- K. Chlichlia
- PubMed: 26849051
- DOI: 10.1371/journal.pone.0147960
Abstract
Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9) CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9) CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain.
Research Insights
| Supplement | Health Outcome | Effect Type | Effect Size |
|---|---|---|---|
| Lacticaseibacillus casei | Increased Apoptotic Cell Death | Beneficial | Large |
| Lacticaseibacillus casei | Increased TRAIL Expression | Beneficial | Moderate |
| Lacticaseibacillus casei | Reduced Colon Cancer Cell Viability | Beneficial | Large |
| Lacticaseibacillus casei | Reduced Survivin Expression | Beneficial | Moderate |
| Lacticaseibacillus casei | Reduced Tumor Growth | Beneficial | Large |
| Lacticaseibacillus casei R0215 | Increased TRAIL Expression | Beneficial | Moderate |
| Lacticaseibacillus casei R0215 | Induction of Apoptotic Cell Death | Beneficial | Large |
| Lacticaseibacillus casei R0215 | Reduced Cancer Cell Viability | Beneficial | Large |
| Lacticaseibacillus casei R0215 | Reduced Colorectal Cancer Cell Proliferation | Beneficial | Large |
| Lacticaseibacillus casei R0215 | Reduced Tumor Growth | Beneficial | Large |
| Lactobacillus casei | Increased Colorectal Cancer Cell Death | Beneficial | Large |
| Lactobacillus casei | Increased TRAIL Expression | Beneficial | Moderate |
| Lactobacillus casei | Reduced Cancer Cell Viability | Beneficial | Large |
| Lactobacillus casei | Reduced Colorectal Cancer Cell Proliferation | Beneficial | Large |
| Lactobacillus casei | Reduced Tumor Growth | Beneficial | Large |
| Lactobacillus casei LC03 | Induction of Apoptotic Cell Death | Beneficial | Large |
| Lactobacillus casei LC03 | Inhibition of Colon Carcinoma Cell Growth | Beneficial | Large |
| Lactobacillus casei LC03 | Reduced Colon Cancer Cell Proliferation | Beneficial | Large |
| Lactobacillus casei PXN 37 | Increased Apoptotic Cell Death | Beneficial | Large |
| Lactobacillus casei PXN 37 | Increased TRAIL Expression | Beneficial | Moderate |
| Lactobacillus casei PXN 37 | Reduced Colon Carcinoma Cell Viability | Beneficial | Large |
| Lactobacillus casei PXN 37 | Reduced Survivin Expression | Beneficial | Moderate |
| Lactobacillus casei PXN 37 | Reduced Tumor Growth | Beneficial | Large |
| Lactobacillus casei R0215 | Increased Apoptosis in Colorectal Cancer Cells | Beneficial | Large |
| Lactobacillus casei R0215 | Reduced Colon Cancer Cell Proliferation | Beneficial | Large |
| Lactobacillus casei R0215 | Reduced Tumor Volume | Beneficial | Large |
| Lactobacillus casei SD-5213 | Increased TRAIL Expression | Beneficial | Moderate |
| Lactobacillus casei SD-5213 | Induction of Apoptotic Cell Death | Beneficial | Large |
| Lactobacillus casei SD-5213 | Reduced Cell Viability | Beneficial | Large |
| Lactobacillus casei SD-5213 | Reduced Tumor Growth | Beneficial | Large |
| Lactobacillus casei SD-5842 | Increased TRAIL Expression | Beneficial | Moderate |
| Lactobacillus casei SD-5842 | Induction of Apoptotic Cell Death | Beneficial | Large |
| Lactobacillus casei SD-5842 | Reduced Cancer Cell Viability | Beneficial | Large |
| Lactobacillus casei SD-5842 | Reduced Survivin Expression | Beneficial | Moderate |
| Lactobacillus casei SD-5842 | Reduced Tumor Volume | Beneficial | Large |
| Lactobacillus casei subsp. casei | Anti-Proliferative Effects on Colon Carcinoma | Beneficial | Large |
| Lactobacillus casei subsp. casei | Increased TRAIL Expression | Beneficial | Moderate |
| Lactobacillus casei subsp. casei | Induction of Apoptotic Cell Death | Beneficial | Large |
| Lactobacillus casei subsp. casei | Reduced Survivin Expression | Beneficial | Moderate |
| Lactobacillus casei subsp. casei | Reduced Tumor Volume | Beneficial | Large |
| Lactobacillus casei UALc-03 | Increased TRAIL Expression | Beneficial | Moderate |
| Lactobacillus casei UALc-03 | Induction of Apoptotic Cell Death | Beneficial | Large |
| Lactobacillus casei UALc-03 | Inhibition of Colon Carcinoma Cell Growth | Beneficial | Large |
| Lactobacillus casei UALc-03 | Reduced Tumor Volume | Beneficial | Large |
| Lactobacillus casei VK4 | Induction of Apoptotic Cell Death | Beneficial | Large |
| Lactobacillus casei VK4 | Reduced Cancer Cell Viability | Beneficial | Large |
| Lactobacillus casei VK4 | Reduced Tumor Growth | Beneficial | Large |