Effects of Forkhead box O1 on lipopolysaccharide‑induced mitochondrial dysfunction in human cervical squamous carcinoma SiHa cells

Abstract

Persistent infection and chronic inflammation play important roles in the development of cervical squamous cell carcinoma. Forkhead box O1 (FOXO1) is a notable regulator of mitochondrial metabolism, which is involved in the occurrence and development of tumors. The present study explored the effects of FOXO1 in human cervical squamous carcinoma SiHa cells. The expression of FOXO1 was examined using reverse transcription-quantitative PCR, western blotting and immunohistochemical staining. SiHa cell migration and proliferation were detected using Transwell and 3 H-TdR assays. Mitochondrial functions were assessed based on reactive oxygen species (ROS) generation and changes in the mitochondrial membrane potential ( ΔΨm ). The present study revealed that lipopolysaccharide (LPS) stimulation significantly inhibited the expression of FOXO1 in cervical squamous carcinoma SiHa cells; while silencing FOXO1 resulted in the accumulation of mitochondrial ROS, a decrease in the ΔΨm and abnormal morphology of mitochondria. Accordingly, enhancing FOXO1 expression or treatment with metformin, which protects mitochondrial function, reversed LPS-induced mitochondrial dysfunction, cell pyroptosis, migration and proliferation of cervical squamous carcinoma SiHa cells. Overall, the current study indicated that treatment with FOXO1 could potentially be used as therapeutic strategy to prevent LPS-induced cervical squamous cell carcinoma-related dysfunction in a mitochondria-dependent manner.

Inhibition of Myocardial Remodeling and Heart Failure by Traditional Herbal Medications: Evidence from Ginseng and ginkgo biloba

“…The authors attributed an anti-inflammatory effect of ginkgolide A possibly via its binding to matrix metallopeptidase 9 [ 84 ]. Ginkgolide A has also been recently shown to attenuate cardiomyopathy in a mouse model of sepsis produced by lipopolysaccharide (LPS) administration as evidenced by a reduced inflammatory response, oxidative stress and apoptosis [ 85 ]. In this report the beneficial effects of ginkgolide A were attributed to its ability to prevent LPS-induced downregulation of nuclear FoxO1, a transcriptional factor responsible for increased expression of cardioprotective genes [ 85 ].…”

“…Ginkgolide A has also been recently shown to attenuate cardiomyopathy in a mouse model of sepsis produced by lipopolysaccharide (LPS) administration as evidenced by a reduced inflammatory response, oxidative stress and apoptosis [ 85 ]. In this report the beneficial effects of ginkgolide A were attributed to its ability to prevent LPS-induced downregulation of nuclear FoxO1, a transcriptional factor responsible for increased expression of cardioprotective genes [ 85 ]. Thus, while this study as well as the study referred to above concerning ginkgolide B [ 83 ] suggest that FoxO1 upregulation is important for the beneficial effects of ginkgolides, it should be added that the role of this transcriptional factor particularly with respect to cardiac hypertrophy and related pathologies is far from completely understood and requires substantial research to delineate [ 86 ].…”

“…A summary of the effects of ginkgo and ginkgolides and their proposed underlying mechanisms is presented in Table 2 (Ref. [ 65 , 66 , 67 , 68 , 69 , 70 , 71 , 73 , 83 , 84 , 85 ]).…”