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. 2017 Nov;14(5):4586-4594.
doi: 10.3892/etm.2017.5105. Epub 2017 Sep 5.

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

Zhou Cheng  1 , Hui Xu  1 , Xiaoping Wang  1 , Zuoye Liu  2
Affiliations

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

Zhou Cheng et al. Exp Ther Med. 2017 Nov.

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 (1.0×103 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 (1.0×103 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.

Keywords: Lactobacillus rhamnosus GG strain; expression; geniposide; human oral keratinocytes; human oral squamous carcinoma HSC-3 cells.

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Figures

Figure 1.
Figure 1.
Effect of Lactobacillus rhamnosus GG strain on the growth of (A) human oral keratinocytes and (B) HSC-3 human oral squamous cell carcinoma cells. CFU, colony-forming units.
Figure 2.
Figure 2.
Effect of geniposide on the growth of (A) human oral keratinocytes and (B) HSC-3 human oral squamous cell carcinoma cells. *P<0.05 and #P<0.01 vs. 0 µg/ml.
Figure 3.
Figure 3.
Apoptotic effects of LGG and geniposide in human oral squamous cell carcinoma HSC-3 cells determined by (A) flow cytometry and (B) DAPI staining (arrows indicate apoptotic nuclei). Magnification, ×50. *P<0.05 and #P<0.01 vs. control group. Groups: Geniposide-L, 25 µg/ml geniposide; LGG-geniposide-L, 1.0×103 CFU/ml LGG + 25 µg/ml geniposide; Geniposide-H, 50 µg/ml geniposide; LGG-geniposide-H, 1.0×103 CFU/ml LGG + 50 µg/ml geniposide. LGG, Lactobacillus rhamnosus GG strain; CFU, colony-forming units.
Figure 4.
Figure 4.
(A) mRNA and (B) protein expression of caspase-3, −8 and −9 in HSC-3 human oral squamous cell carcinoma cells. *P<0.05 and #P<0.01 vs. control group. Groups: Geniposide-L, 25 µg/ml geniposide; LGG-geniposide-L, 1.0×103 CFU/ml LGG + 25 µg/ml geniposide; Geniposide-H, 50 µg/ml geniposide; LGG-geniposide-H, 1.0×103 CFU/ml LGG + 50 µg/ml geniposide. LGG, Lactobacillus rhamnosus GG strain; CFU, colony-forming units.
Figure 5.
Figure 5.
(A) mRNA and (B) protein expression of Bax, Bcl-2 and Bcl-xL in human oral squamous carcinoma HSC-3 cells. *P<0.05 and #P<0.01 vs. control group. Groups: Geniposide-L, 25 µg/ml geniposide; LGG-geniposide-L, 1.0×103 CFU/ml LGG + 25 µg/ml geniposide; Geniposide-H, 50 µg/ml geniposide; LGG-geniposide-H, 1.0×103 CFU/ml LGG + 50 µg/ml geniposide. LGG, Lactobacillus rhamnosus GG strain; Bcl-2, B-cell lymphoma 2; Bax, Bcl-2-associated X protein; Bcl-xL, Bcl-extra large protein; CFU, colony-forming units.
Figure 6.
Figure 6.
(A) mRNA and (B) protein expression of Fas and FasL in human oral squamous carcinoma HSC-3 cells. *P<0.05 and #P<0.01 vs. control group. Groups: Geniposide-L, 25 µg/ml geniposide; LGG-geniposide-L, 1.0×103 CFU/ml LGG + 25 µg/ml geniposide; Geniposide-H, 50 µg/ml geniposide; LGG-geniposide-H, 1.0×103 CFU/ml LGG + 50 µg/ml geniposide. LGG, Lactobacillus rhamnosus GG strain; FasL, Fas ligand; CFU, colony-forming units.
Figure 7.
Figure 7.
(A) mRNA and (B) protein expression of p53 and p21 in human oral squamous carcinoma HSC-3 cells. *P<0.05 and #P<0.01 vs. control group. Groups: Geniposide-L, 25 µg/ml geniposide; LGG-geniposide-L, 1.0×103 CFU/ml LGG + 25 µg/ml geniposide; Geniposide-H, 50 µg/ml geniposide; LGG-geniposide-H, 1.0×103 CFU/ml LGG + 50 µg/ml geniposide. LGG, Lactobacillus rhamnosus GG strain; CFU, colony-forming units.
Figure 8.
Figure 8.
(A) mRNA and (B) protein expression of HIAP-1 and HIAP-2 in human oral squamous carcinoma HSC-3 cells. *P<0.05 and #P<0.01 vs. control group. Groups: Geniposide-L, 25 µg/ml geniposide; LGG-geniposide-L, 1.0×103 CFU/ml LGG + 25 µg/ml geniposide; Geniposide-H, 50 µg/ml geniposide; LGG-geniposide-H, 1.0×103 CFU/ml LGG + 50 µg/ml geniposide. LGG, Lactobacillus rhamnosus GG strain; HIAP, human inhibitor of apoptosis; CFU, colony-forming units.
Figure 9.
Figure 9.
(A) mRNA and (B) protein expression of NF-κB and IκB-α in human oral squamous carcinoma HSC-3 cells. *P<0.05 and #P<0.01 vs. control group. Groups: Geniposide-L, 25 µg/ml geniposide; LGG-geniposide-L, 1.0×103 CFU/ml LGG + 25 µg/ml geniposide; Geniposide-H, 50 µg/ml geniposide; LGG-geniposide-H, 1.0×103 CFU/ml LGG + 50 µg/ml geniposide. LGG, Lactobacillus rhamnosus GG strain; NF-κB, nuclear factor-κB; I-κB-α, inhibitor of NF-κB α; CFU, colony-forming units.
Figure 10.
Figure 10.
The mRNA (A) and protein (B) expression of COX-2 and iNOS in human oral squamous carcinoma HSC-3 cells. *P<0.05 and #P<0.01 vs. control group. Groups: Geniposide-L, 25 µg/ml geniposide; LGG-geniposide-L, 1.0×103 CFU/ml LGG + 25 µg/ml geniposide; Geniposide-H, 50 µg/ml geniposide; LGG-geniposide-H, 1.0×103 CFU/ml LGG + 50 µg/ml geniposide. LGG, Lactobacillus rhamnosus GG strain; COX, cyclooxygenase; iNOS, inducible nitric oxide synthase; CFU, colony-forming units.
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