Anti-Tumor Effects of Heat-Killed L. reuteri MG5346 and L. casei MG4584 against Human Colorectal Carcinoma through Caspase-9-Dependent Apoptosis in Xenograft Model

In this study, we examined the anti-tumor effects of heat-killed and strains on human colorectal carcinoma RKO cells in in vitro and in vivo xenograft models. First, the cytotoxic and apoptotic effects of 11 different strains were examined using an MTT assay and flow cytometry, respectively. Then, x...

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Bibliographic Details
Published in:Microorganisms (Basel) 2022-02, Vol.10 (3), p.533
Main Authors: Kim, Suk-Jin, Kang, Chang-Ho, Kim, Gun-Hee, Cho, Hyosun
Format: Article
Language:English
Subjects:
Anticancer properties
Apoptosis
Bacteria
Cancer
Caspase-3
Caspase-9
Chemotherapy
Colorectal cancer
Colorectal carcinoma
Cytotoxicity
Drinking water
Flow cytometry
Heat
Immunohistochemistry
Laboratory animals
Morphology
Oral administration
parabiotics
Penicillin
Poly(ADP-ribose) polymerase
Probiotics
Proteins
Staining
Strains (organisms)
Tumors
Western blotting
xenograft
Xenografts
Xenotransplantation
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Summary:In this study, we examined the anti-tumor effects of heat-killed and strains on human colorectal carcinoma RKO cells in in vitro and in vivo xenograft models. First, the cytotoxic and apoptotic effects of 11 different strains were examined using an MTT assay and flow cytometry, respectively. Then, xenograft BALB/c nude mice were implanted with RKO cells and orally administered with single or mixed heat-killed bacterial strains to examine their inhibitory effects on tumor growth. Additionally, the levels of cleaved caspase-9, -3, and -7 and PARP in tumor tissues were analyzed using Western blotting or immunohistochemistry staining. The results showed that RKO cells were highly susceptible to heat-killed MG731 and MG5346 and that MG4584 induced apoptosis to a greater extent than other strains. The oral administration of individual MG731, MG5346, or MG4584 significantly delayed tumor growth, and mixtures of MG5346 and MG4584 or MG731, MG5346, and MG4584 synergistically inhibited the tumor growth in the xenograft model. The expression of cleaved caspase-3, -7, and -9 and PARP in the tumor tissues was increased in Western blotting, and the expression of cleaved caspase-3 and PARP in immunohistochemistry staining was also increased. Therefore, we suggest that the use of the combination of MG5346 and MG4584 as parabiotics could effectively inhibit the growth of colorectal cancer.
ISSN:2076-2607
2076-2607
DOI:10.3390/microorganisms10030533