Lactobacillus raises in vitro anticancer effect of geniposide in HSC‑3 human oral squamous cell carcinoma cells

Abstract

Abstract. The present study determined the ability of the Lactobacillus rhamnosus GG strain (LGG) to enhance the anticancer effects of geniposide on HSC-3 human oral squamous carcinoma cells.LGG (1.0x10 3 CFU/ml) on its own had no impact on human oral keratinocytes and HSC-3 cancer cells. Geniposide (25 or 50 µg/ml) had no impact on human oral keratinocytes, but exerted growth inhibitory effects on HSC-3 cancer cells, which were increased in the presence of LGG. Flow cytometric analysis and a nuclear staining assay with DAPI revealed that HSC-3 cancer cells treated with LGG-geniposide (1.0x10 3 CFU/ml LGG and 50 µg/ml geniposide) had a higher apoptotic rate than cells in other treatment groups, particularly that treated with geniposide (50 µg/ml) only. Geniposide also increased the mRNA and protein expression of caspase-3, -8 and -9 as well as B-cell lymphoma 2 (Bcl-2)-associated X protein, p53, p21, inhibitor of nuclear factor-κB (NF-κB) α, Fas and Fas ligand, while decreasing Bcl-2, Bcl extra large protein, inhibitor of apoptosis-1 and -2, NF-κB, cyclooxigenase-2 and inducible nitric oxide synthase in HSC-3 cells, which was increased in the presence of LGG. These results indicated that LGG enhanced the anticancer effects of geniposide in HSC-3 cells. IntroductionGardenia jasminoides Ellis belongs to the Rubiaceae family and Gardenia genus, and its dried ripe fruit can be used as a medicine, with bitter and cold taste, and nourishing the heart, lungs and San Juao meridian according to the principles of Chinese Medicine (1). Gardenia fruit mainly protects the liver and nourishes the gallbladder, and its active constituent is geniposide, which belongs to the iridoid glycosides (2). It is also rich in other constituents such as organic acids, pigments and volatile oils (3). A pharmacokinetic study has found that geniposide, the active constituent of Gardenia jasminoides Ellis, is hydrolyzed by β-glucosidase produced by intestinal microorganisms to generate genipin (4). Studies have proved that genipin also significantly reduces inflammation, lipid peroxidation and angiogenesis, with low cytotoxicity, sound biocompatibility and high anti-degradation ability (5,6). Gardenia jasminoides Ellis has a low genipin content, which only accounts for 0.005-0.01%, and mainly exists in the form of its precursor-geniposide, accounting for 3-5%. At present, geniposide is extracted with organic solvents, and 100 g gardenia fruit provide ~4 g geniposide. Therefore, it is of great significance to ferment Gardenia by microorganisms to produce genipin (7). In addition, the use of microorganisms and geniposide may achieve a better control of the concentration of active constituents, which may enhance the pharmacological effect. The transformation of geniposide contained in Gardenia jasminoides by fermentation with microorganisms is carried out by β-glucosidase produced by bacteria, which breaks chemical bonds in geniposide to produce genipin (8).In the present study, high-yield lactobacillus produced by β-glucosidase was used to react...

Role of <em>Lactobacillus</em> in cervical cancer

“…In addition to cervical cancer, Lactobacillus is associated with the proliferation and regulation of cells of other cancer types, such as breast cancer, 32 colorectal cancer, 33 gastric cancer, 34 and oral cancer. 35 , 36 Observations in these other cancers may offer insights into the study of Lactobacillus in cervical cancer. The main observations regarding Lactobacillus in cancers are as follows: 1) Lactobacillus can activate and strengthen the antitumor effects of immunocytes such as thymus-derived cells (T cells), natural killer (NK) cells, dendritic cells (DCs), and macrophages and immunological factors produced by immunocytes; 37 – 39 2) a large amount of unmethylated dinucleotide repeat sequences present in the nuclei of Lactobacillus can activate the innate immune response by binding to a specific receptor that exists on the surface of human cells; 40 3) Lactobacillus that is suitable for reproduction and growth in an anaerobic environment can selectively accumulate in the hypoxic zones of solid cancers; 41 and 4) Lactobacillus can selectively locate to solid cancers and can be used as a vector for gene therapy and targeted therapies.…”

Retracted: Geniposide exhibits anticancer activity to medulloblastoma cells by downregulating microRNA‐373

“…Geniposide (purity >99.9%) was obtained from National Institute for the Control of Pharmaceutical and Biological Products (Jilin, China) and diluted with phosphate‐buffered saline (PBS) to a concentration of 5 mg/mL. According to previous literature, [ 33 ] we treated the cells with a concentration of 50 μg/mL geniposide. However, the 50‐μg/mL geniposide treatment had no obvious effect on medulloblastoma cell viability.…”

Association of oral dysbiosis with oral cancer development (Review)

“…To the best of our knowledge, few data have been generated about the effects of probiotics in oral cancer development. Of note, the results of a previous study demonstrated that the administration of Lactobacillus rhamnosus GG (LGG) was able to increase the effects of geniposide, an anticancer molecule tested on human oral squamous carcinoma cells (HSC-3), demonstrating the beneficial role of LGG as potential adjuvant of geniposide treatment (58).…”

“…Few data are available on the effects of probiotics on oral cancer. In a recent study, HSC-3 OSCC cell lines were used to determine the effects of Lactobacillus rhamnosus GG (LGG) in increasing the antiblastic effects of geniposide, a derivate of Gardenia jasminoides which in preclinical studies showed important anticancer effects (58,195). The results obtained by the authors showed that the combined treatment with geniposide and LGG increased the apoptotic rate of HSC-3 cells.…”