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A pentacyclic triterpene natural product, ursolic acid and its prodrug US597 inhibit targets within cell adhesion pathway and prevent cancer metastasis.

Xiang L, Chi T, Tang Q, Yang X, Ou M, Chen X, Yu X, Chen J, Ho RJ, Shao J, Jia L - Oncotarget (2015)

Bottom Line: Immunohistochemical analysis revealed that US597 treatment regulates ICAM-1, a biomarker of metastasis.We did not detect side effects with US597 in mice such as weight loss, viscera tissues toxicity and blood cell abnormalities.Thus, UA and US597 are potential drug candidates for preventing cancer metastasis.

View Article: PubMed Central - PubMed

Affiliation: Cancer Metastasis Alert and Prevention Center and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.

ABSTRACT
Here we showed that ursolic acid (UA), a pentacyclic triterpene natural product, and its novel prodrug derivative US597 suppressed cancer cells adhesion, invasion and migration. This effect was accompanied by inhibition of focal adhesion signaling pathway including alterations in ICAM-1, VCAM-1, E-selectin, P-selectin, integrin α6β1, FAK, Src, paxillin and PTEN. While oral administration of UA or US597 increases survival rate of melanoma lung metastasis in C57BL/6 mice, US597 treatment extend the survival rate above that of UA. Immunohistochemical analysis revealed that US597 treatment regulates ICAM-1, a biomarker of metastasis. We did not detect side effects with US597 in mice such as weight loss, viscera tissues toxicity and blood cell abnormalities. Thus, UA and US597 are potential drug candidates for preventing cancer metastasis. Molecular and cellular study data suggest that UA and US597 modulate expression of cell adhesion molecules within focal adhesion signaling pathway leading to cancer cell motility.

No MeSH data available.


Related in: MedlinePlus

(A) Immunostaining with antibodies to ICAM-1 was performed on lung sections from mice(B) Quantitative of the mean ICAM-1 positive area counted at original magnification × 200, the results were expressed as mean ± SD (n = 3). *P < 0.05, **P < 0.01 vs control. (C) The plasma concentration-time curves of US597 and UA in Sprague-Dawley rats (n = 5) after a single oral dose of 80 mg/kg US597.
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Figure 8: (A) Immunostaining with antibodies to ICAM-1 was performed on lung sections from mice(B) Quantitative of the mean ICAM-1 positive area counted at original magnification × 200, the results were expressed as mean ± SD (n = 3). *P < 0.05, **P < 0.01 vs control. (C) The plasma concentration-time curves of US597 and UA in Sprague-Dawley rats (n = 5) after a single oral dose of 80 mg/kg US597.

Mentions: Inhibition of ICAM-1 expression in lung tissue was determined by immunohistochemical staining (Figure 8A). ICAM-1 expression was appreciably enhanced in endothelial cells of blood vessels in the control group. Compared with the control group, there was no significant changes in the low dose US597 group (P > 0.05 Figure 8B). The expressions of ICAM-1 were significantly decreased in the UA and high dose US597 group (P < 0.01 Figure 8B).


A pentacyclic triterpene natural product, ursolic acid and its prodrug US597 inhibit targets within cell adhesion pathway and prevent cancer metastasis.

Xiang L, Chi T, Tang Q, Yang X, Ou M, Chen X, Yu X, Chen J, Ho RJ, Shao J, Jia L - Oncotarget (2015)

(A) Immunostaining with antibodies to ICAM-1 was performed on lung sections from mice(B) Quantitative of the mean ICAM-1 positive area counted at original magnification × 200, the results were expressed as mean ± SD (n = 3). *P < 0.05, **P < 0.01 vs control. (C) The plasma concentration-time curves of US597 and UA in Sprague-Dawley rats (n = 5) after a single oral dose of 80 mg/kg US597.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496218&req=5

Figure 8: (A) Immunostaining with antibodies to ICAM-1 was performed on lung sections from mice(B) Quantitative of the mean ICAM-1 positive area counted at original magnification × 200, the results were expressed as mean ± SD (n = 3). *P < 0.05, **P < 0.01 vs control. (C) The plasma concentration-time curves of US597 and UA in Sprague-Dawley rats (n = 5) after a single oral dose of 80 mg/kg US597.
Mentions: Inhibition of ICAM-1 expression in lung tissue was determined by immunohistochemical staining (Figure 8A). ICAM-1 expression was appreciably enhanced in endothelial cells of blood vessels in the control group. Compared with the control group, there was no significant changes in the low dose US597 group (P > 0.05 Figure 8B). The expressions of ICAM-1 were significantly decreased in the UA and high dose US597 group (P < 0.01 Figure 8B).

Bottom Line: Immunohistochemical analysis revealed that US597 treatment regulates ICAM-1, a biomarker of metastasis.We did not detect side effects with US597 in mice such as weight loss, viscera tissues toxicity and blood cell abnormalities.Thus, UA and US597 are potential drug candidates for preventing cancer metastasis.

View Article: PubMed Central - PubMed

Affiliation: Cancer Metastasis Alert and Prevention Center and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.

ABSTRACT
Here we showed that ursolic acid (UA), a pentacyclic triterpene natural product, and its novel prodrug derivative US597 suppressed cancer cells adhesion, invasion and migration. This effect was accompanied by inhibition of focal adhesion signaling pathway including alterations in ICAM-1, VCAM-1, E-selectin, P-selectin, integrin α6β1, FAK, Src, paxillin and PTEN. While oral administration of UA or US597 increases survival rate of melanoma lung metastasis in C57BL/6 mice, US597 treatment extend the survival rate above that of UA. Immunohistochemical analysis revealed that US597 treatment regulates ICAM-1, a biomarker of metastasis. We did not detect side effects with US597 in mice such as weight loss, viscera tissues toxicity and blood cell abnormalities. Thus, UA and US597 are potential drug candidates for preventing cancer metastasis. Molecular and cellular study data suggest that UA and US597 modulate expression of cell adhesion molecules within focal adhesion signaling pathway leading to cancer cell motility.

No MeSH data available.


Related in: MedlinePlus