Antiangiogenic Potential of Three Triterpenic Acids in Human Liver Cancer Cells

Lin, Chih Kuang; Huang, Chun‐Yin; Mong, Mei-Chin; Chan, Cho‐Yu; Yin, Mei‐chin

doi:10.1021/jf103904b

Cited by 94 publications

(67 citation statements)

References 38 publications

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“…Interestingly, it has been recently shown that ursolic acid enriched in NFJ and also in many other plant products suppresses endogenous mRNA expression of multiple pro-angiogenic genes, including HIF-1α, in human liver cancer cells (28), thereby suggesting its antiangiogenic potential. Though not assessed herein, it is suggested that among the constituents of noni juice, ursolic acid may be a key compound associated with the NFJ's repressive effect on the manganese-induced HIF-1α protein expression in A549 cells.…”

Section: Discussionmentioning

confidence: 99%

The fruit juice of Morinda citrifolia (noni) downregulates HIF-1α protein expression through inhibition of PKB, ERK-1/2, JNK-1 and S6 in manganese-stimulated A549 human lung cancer cells

Jang

2011

Int J Mol Med

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Abstract. High exposure of manganese is suggested to be a risk factor for many lung diseases. Evidence suggests anticancerous and antiangiogenic effects by products derived from Morinda citrifolia (noni) fruit. In this study, we investigated the effect of noni fruit juice (NFJ) on the expression of HIF-1α, a tumor angiogenic transcription factor in manganese-chloride (manganese)-stimulated A549 human lung carcinoma cells. Treatment with manganese largely induced expression of HIF-1α protein but did not affect HIF-1α mRNA expression in A549 cells, suggesting the metal-mediated co-and/or post-translational HIF-1α upregulation. Manganese treatment also led to increased phosphorylation of extracellular-regulated protein kinase-1/2 (ERK-1/2), c-Jun N-terminal kinase-1 (JNK-1), protein kinase B (PKB), S6 and eukaryotic translation initiation factor-2α (eIF-2α) in A549 cells. Of note, the exposure of NFJ inhibited the manganese-induced HIF-1α protein upregulation in a concentration-dependent manner. Importantly, as assessed by results of pharmacological inhibition and siRNA transfection studies, the effect of NFJ on HIF-1α protein downregulation seemed to be largely associated with the ability of NFJ to interfere with the metal's signaling to activate PKB, ERK-1/2, JNK-1 and S6 in A549 cells. It was further shown that NFJ could repress the induction of HIF-1α protein by desferoxamine or interleukin-1β (IL-1β), another HIF-1α inducer in A549 cells. Thus, the present study provides the first evidence that NFJ has the ability to strongly downregulate manganese-induced HIF-1α protein expression in A549 human lung cancer cells, which may suggest the NFJ-mediated beneficial effects on lung pathologies in which manganese and HIF-1α overexpression play pathogenic roles.

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Section: Discussionmentioning

confidence: 99%

The fruit juice of Morinda citrifolia (noni) downregulates HIF-1α protein expression through inhibition of PKB, ERK-1/2, JNK-1 and S6 in manganese-stimulated A549 human lung cancer cells

Jang

2011

Int J Mol Med

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“…Ramos et al (2008) found that UA prevented DNA damage via increase of DNA repair and anti-proliferative properties in HepG2 cells. Lin et al (2011) found that UA reversed the invasion and migration of Hep3B and Huh7 cell lines at 4 lmol/ L. Son et al (2013) reported that UA blocked HepG2 cellular metabolism via AMPK activation and GSK3b phosphorylation, and thus induced apoptosis of HepG2 cells. On the suppression of carcinogenic side, UA could prevent HCC from nonalcoholic fatty liver disease (NAFLD), insulin resistance, inflammation and oxidation stress.…”

Section: Introductionmentioning

confidence: 99%

Anti-hepatocellular carcinoma activity and mechanism of chemopreventive compounds: ursolic acid derivatives

Huang

Chen

Ren

et al. 2016

Pharmaceutical Biology

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Context: Hepatocellular carcinoma (HCC) is a common cancer around the world, with high mortality rate. Currently, there is no effective drug for the therapy of HCC. Ursolic acid (UA) is a natural product which exists in various medicinal herbs and fruits, exhibiting multiple biological effects such as its outstanding anticancer and hepatoprotective activity, which has drawn many pharmacists' attention. Objective: This paper summarizes the current status of the hepatoprotective activity of UA analogues and explains the related mechanism, providing a clear direction for the development of novel anti-HCC drugs. Methods: All of the data resources were derived from PubMed. By comparing the IC 50 values and analyzing the structure-activity relationships, we listed compounds with good pharmacological activity from the relevant literature, and summarized their anti-HCC mechanism. Results: From the database, 58 new UA derivatives possessing wonderful anticancer and hepatoprotective effects were listed, and the relevant anti-HCC mechanism were discussed. Conclusion: UA's anti-HCC effect is the result of combined action of many mechanisms. These 58 new UA derivatives, particularly compounds 45 and 53, can be used as potential drugs for the treatment of liver cancer. ARTICLE HISTORY

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“…Lin et al used UA to treat human liver cancer (i.e., Hep3B, Huh7, and HA22T cells) cell lines, and found that the expressions of HIF-1, VEGF, and IL-8 significantly reduced in a dose-dependent manner. Additionally, cell invasion and migration were also found to have declined along with the suppressed expression of uPA [46]. In vitro and in vivo studies by Kanjoormana et al revealed the anti-angiogenic characteristics of UA: UA inhibited capillary formation of the tumor induced by highly metastatic melanoma (B16F-10) cells in C57BL/6 mice.…”

Section: Anti-angiogenesismentioning

confidence: 99%