Inhibition of human vascular endothelial cells proliferation by terbinafine

Ho, Pei Yin; Liang, Yu Chih; Ho, Yuan Soon; Chen, Chiung Tong; Lee, Wen Sen

doi:10.1002/ijc.20039

Cited by 34 publications

(25 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously, we showed that terbinafine at a range of concentrations (30 -120 Amol/L) dose dependently inhibited angiogenesis by suppressing the proliferation of HUVEC and capillary-like tube formation in vitro and sprouting angiogenesis in vivo (8). Here, we further showed that terbinafine (30 -120 Amol/L) dose dependently inhibited HUVEC adhesion and migration.…”

Section: Discussionmentioning

confidence: 52%

“…These findings suggest that inhibition of cell adhesion could contribute only partially to endothelial migration inhibition induced by terbinafine treatment. Moreover, our previous study showed that terbinafine at a concentration of 120 Amol/L did not cause any cell death in HUVEC (8), suggesting that the terbinafine-induced endothelial migration inhibition was not due to cytotoxicity.…”

Section: Discussionmentioning

confidence: 88%

“…We also found that terbinafine could inhibit the proliferation of cultured human umbilical vascular endothelial cell (HUVEC), the capillary-like tube formation, and sprouting of capillary. The terbinafine-induced cell cycle arrest in HUVEC occurred when the activity of cyclindependent kinase 2 was inhibited just as the protein level of p21 was increased and cyclin A was decreased (8). In the present study, we continued to study the mechanism of terbinafine-induced antiangiogenic activity by examining the effect of terbinafine on HUVEC adhesion and migration.…”

Section: Introductionmentioning

confidence: 87%

“…Western Blot Analysis To determine the expression levels of focal adhesion kinase (FAK), paxillin, Ras, RhoA, RhoB, RhoC, and glyceraldehyde-3-phosphate dehydrogenase (G3PDH) in HUVEC, the total proteins were extracted, and Western blot analyses were done as described previously (8). Briefly, HUVEC were cultured in 15-cm Petri dishes.…”

Section: Subcellular Fractionationmentioning

confidence: 99%

“…Comparisons were subjected to one-way ANOVA followed by Fisher's least significant difference test. Significance was accepted at P < 0.05. endothelial cells (8). To examine whether inhibition of endothelial cell migration is also involved in the terbinafine-induced inhibition of angiogenesis, a Transwell migration assay was done in HUVEC.…”

Section: Subcellular Fractionationmentioning

confidence: 99%

See 4 more Smart Citations

Terbinafine inhibits endothelial cell migration through suppression of the Rho-mediated pathway

Ho¹,

Wang²,

et al. 2006

Molecular Cancer Therapeutics

Self Cite

View full text Add to dashboard Cite

We showed previously that terbinafine, an allylamine with fungicidal activity, could inhibit angiogenesis by suppressing the endothelial cell proliferation. In the present study, we further showed that terbinafine (0 -120 Mmol/L) dose dependently inhibited the adhesion and migration of human umbilical vascular endothelial cells (HUVEC). Western blot analysis showed that terbinafine decreased the levels of Ras protein and membrane-bound RhoA protein. Moreover, the terbinafine-induced migration inhibition in HUVEC was prevented by pretreatment with farnesol or geranylgeraniol. Pretreatment of HUVEC with Ras inhibitor peptide or a ROCK (a kinase associated with RhoA for transducing RhoA signaling) inhibitor, Y27632, abolished the farnesol-or geranylgeraniol-induced prevention effect on the terbinafine-induced migration inhibition, respectively. These data suggest that the consuming or depletion of geranylgeranyl pyrophosphate and consequent suppression of protein geranylgeranylation and farnesylation, which is essential for activation of Rho GTPases and Ras, respectively, might account for the terbinafine-induced inhibition of HUVEC migration. The levels of phosphorylated focal adhesion kinase and paxillin protein and the mRNA levels of matrix metalloproteinase-2 and matrix metalloproteinase-9 were also decreased by terbinafine treatment. Taken together, these results indicate that suppression of Rho-mediated pathway might be involved in the signal transduction leading to the inhibition of cell migration caused by terbinafine in HUVEC. [Mol Cancer Ther 2006;5(12):3130 -8]

show abstract

Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 87%

Section: Subcellular Fractionationmentioning

confidence: 99%

Section: Subcellular Fractionationmentioning

confidence: 99%

See 3 more Smart Citations

Terbinafine inhibits endothelial cell migration through suppression of the Rho-mediated pathway

Ho¹,

Wang²,

et al. 2006

Molecular Cancer Therapeutics

Self Cite

View full text Add to dashboard Cite

show abstract

Squalene epoxidase promotes colorectal cancer cell proliferation through accumulating calcitriol and activating CYP24A1‐mediated MAPK signaling

Pan

et al. 2021

Cancer Communications

View full text Add to dashboard Cite

Background Colorectal cancer (CRC) is one of the most malignant tumors with high incidence, yet its molecular mechanism is not fully understood, hindering the development of targeted therapy. Metabolic abnormalities are a hallmark of cancer. Targeting dysregulated metabolic features has become an important direction for modern anticancer therapy. In this study, we aimed to identify a new metabolic enzyme that promotes proliferation of CRC and to examine the related molecular mechanisms. Methods We performed RNA sequencing and tissue microarray analyses of human CRC samples to identify new genes involved in CRC. Squalene epoxidase (SQLE) was identified to be highly upregulated in CRC patients. The regulatory function of SQLE in CRC progression and the therapeutic effect of SQLE inhibitors were determined by measuring CRC cell viability, colony and organoid formation, intracellular cholesterol concentration and xenograft tumor growth. The molecular mechanism of SQLE function was explored by combining transcriptome and untargeted metabolomics analysis. Western blotting and real‐time PCR were used to assess MAPK signaling activation by SQLE. Results SQLE‐related control of cholesterol biosynthesis was highly upregulated in CRC patients and associated with poor prognosis. SQLE promoted CRC growth in vitro and in vivo. Inhibition of SQLE reduced the levels of calcitriol (active form of vitamin D3) and CYP24A1, followed by an increase in intracellular Ca2+ concentration. Subsequently, MAPK signaling was suppressed, resulting in the inhibition of CRC cell growth. Consistently, terbinafine, an SQLE inhibitor, suppressed CRC cell proliferation and organoid and xenograft tumor growth. Conclusions Our findings demonstrate that SQLE promotes CRC through the accumulation of calcitriol and stimulation of CYP24A1‐mediated MAPK signaling, highlighting SQLE as a potential therapeutic target for CRC treatment.

show abstract

Use of terbinafine and risk of death in patients with prostate cancer: A population‐based cohort study

Sundquist

2018

Intl Journal of Cancer

View full text Add to dashboard Cite

Terbinafine is used for the treatment of several superficial fungal infections. In silico analyses and animal models suggest that terbinafine might have an anti‐tumor effect. We aimed to explore whether subsequent administration of terbinafine might be associated with a lower mortality rate in patients with prostate cancer. We identified patients diagnosed with prostate cancer between July 2005 and December 2014 from the Swedish Cancer Registry, and linked them to the Swedish Prescribed Drug Register to ascertain subsequent use of terbinafine. A total of 799 patients received oral treatment of terbinafine during the study period with a mortality rate of 18.6 per 1,000 person‐years. Compared to patients who did not use terbinafine and adjusting for a range of confounding factors, patients that received oral treatment of terbinafine had a decreased risk of death from prostate cancer (HR, 0.53; 95% CI, 0.38–0.73) and a decreased risk of death overall (HR, 0.64; 95% CI, 0.52–0.77). To account for indication bias, we further identified 907 patients who received topical use of terbinafine. However, the risk of death from prostate cancer in patients with topical use of terbinafine was 0.92 (95% CI 0.74–1.12) and the risk of death overall was 1.03 (95% CI 0.91–1.17) as compared to the controls, which suggests that there was no association between risk of death in patients with prostate cancer with topical use of terbinafine. These findings suggest that this drug's potential anti‐tumor effect needs to be explored further.

show abstract

Inhibition of human vascular endothelial cells proliferation by terbinafine

Cited by 34 publications

References 36 publications

Terbinafine inhibits endothelial cell migration through suppression of the Rho-mediated pathway

Terbinafine inhibits endothelial cell migration through suppression of the Rho-mediated pathway

Squalene epoxidase promotes colorectal cancer cell proliferation through accumulating calcitriol and activating CYP24A1‐mediated MAPK signaling

Use of terbinafine and risk of death in patients with prostate cancer: A population‐based cohort study

Contact Info

Product

Resources

About