A novel benzimidazole analogue inhibits the hypoxia-inducible factor (HIF)-1 pathway

Won, Misun; Im, Namhui; Park, Soo-Hyun; Boovanahalli, Shanthaveerappa K.; Jin, Yinglan; Jin, Xuejun; Chung, Kyung‐Sook; Kang, Minho; Lee, Kiho; Park, Song‐Kyu; Kim, Hwan Mook; Kwon, Byoung Mog; Lee, Jun Young; Lee, Kyeong

doi:10.1016/j.bbrc.2009.05.022

Cited by 52 publications

(35 citation statements)

References 33 publications

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“…Therefore, PPZ may suppress SGC-7901 cancer cells by downregulating the V-ATPases/mTOR/HIF-1α/PKM2 signaling pathway. Alternatively, as benzimidazole compounds, which were found to regulate the stability of HIF-1α through the Hsp90-Akt pathway (31), PPZ may indirectly reduce the protein expression of PKM2 by inhibiting HIF-1α expression. Therefore, the inhibitory effects of PPZ on the PKM2 protein may involve a variety of factors.…”

Section: Discussionmentioning

confidence: 99%

Pantoprazole inhibits human gastric adenocarcinoma SGC-7901 cells by downregulating the expression of pyruvate kinase M2

et al. 2015

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Abstract. The Warburg effect is important in tumor growth. The human M2 isoform of pyruvate kinase (PKM2) is a key enzyme that regulates aerobic glycolysis in tumor cells. Recent studies have demonstrated that PKM2 is a potential target for cancer therapy. The present study investigated the effects of pantoprazole (PPZ) treatment and PKM2 transfection on human gastric adenocarcinoma SGC-7901 cells in vitro. The present study revealed that PPZ inhibited the proliferation of tumor cells, induced apoptosis and downregulated the expression of PKM2, which contributes to the current understanding of the functional association between PPZ and PKM2. In summary, PPZ may suppress tumor growth as a PKM2 protein inhibitor.

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Section: Discussionmentioning

confidence: 99%

Pantoprazole inhibits human gastric adenocarcinoma SGC-7901 cells by downregulating the expression of pyruvate kinase M2

et al. 2015

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“…The PPZ could inhibit tumor cell proton pump, change the acidification of tumor microenvironment [34] and increase VHL expression, which by the way so that increased the degradation of HIF-1α. On the other hand, benzimidazole analogue was found to regulate the stability of HIF-1α through the Hsp90-Akt pathway, leading to the degradation of HIF-1α [35], and we concluded that PPZ might inhibit HIF-1α expression as a kind of benzimidazole compounds. In a word, the inhibitory effects of PPZ on HIF-1α protein may involve several different factors.…”

Section: Discussionmentioning

confidence: 77%

“…Recent years witnessed considerable progress in numerous related experimental studies targeting HIF-1α , such as inhibiting HIF-1α protein on gene level by RNA interference [36], suppressing the expression of HIF-1α by various drugs (mostly on post-transcriptional level, equaling the protein level) [35], and hydroxylating HIF-1 to induce the degradation of HIF-1α under normoxia [37]. As a result, the research on anticancer therapy is getting more and more intensive.…”

Section: Discussionmentioning

confidence: 99%

Effects of pantoprazole as a HIF-1α inhibitor on human gastric adenocarcinoma sgc-7901 cells

Shen

Wu²,

Chen³

et al. 2012

neo

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Previously, it has been demonstrated that HIF-1α has close connection with malignant tumor progression, aggressive behavior and prognosis. In addition, proton pump inhibitors (PPIs) have been reported to selectively induce tumor cell apoptosis, thus exerting its anticancer effects. In vitro and in vivo our study revealed that pantoprazole (PPZ) inhibited tumor cells proliferation, induced apoptosis and decreased the expression of HIF-1α protein. In summary, PPZ could suppress tumor growth acting as a HIF-1α protein inhibitor.

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“…Transactivation of RhoB was determined by a reporter assay using a dual-luciferase reporter assay system (Promega, Madison, WI, USA), as previously described [18]. HeLa cells at 75-90% confluence were transiently cotransfected with the pGL2-RhoB-luciferase plasmid containing the RhoB promoter and pRL-SV40 encoding firefly renilla luciferase.…”

Section: Luciferase Assaymentioning

confidence: 99%

NSC126188, a piperazine alkyl derivative, induces apoptosis via upregulation of RhoB in HeLa cells

Kim

Chung

et al. 2010

Invest New Drugs

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We describe here a piperazine alkyl derivative, NSC126188, which induced apoptosis of HeLa cells by upregulating RhoB expression. NSC126188 caused multi-septation of fission yeast and hypersensitized a ∆rho3 mutant, which implicates the involvement of functional human homolog RhoB. The treatment of cells with NSC126188 induced apoptosis and a dramatic increase in RhoB expression. In addition, RhoB knockdown using siRNA rescued cells from apoptosis, indicating a crucial role of RhoB in NSC126188-induced apoptosis. In a reporter assay using luciferase and EGFP under control of the RhoB promoter, NSC126188 increased both luciferase activity and the expression of EGFP, implicating transcriptional activation of RhoB by NSC126188. Furthermore, NSC126188 demonstrated in vivo anti-tumor activity, inhibiting tumor growth by 66.8% in a nude mouse xenograft using PC-3 human prostate cancer cells. These results suggest that NSC126188 is a potential lead compound and that upregulation of RhoB is associated with NSC126188-induced apoptosis.

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A novel benzimidazole analogue inhibits the hypoxia-inducible factor (HIF)-1 pathway

Cited by 52 publications

References 33 publications

Pantoprazole inhibits human gastric adenocarcinoma SGC-7901 cells by downregulating the expression of pyruvate kinase M2

Pantoprazole inhibits human gastric adenocarcinoma SGC-7901 cells by downregulating the expression of pyruvate kinase M2

Effects of pantoprazole as a HIF-1α inhibitor on human gastric adenocarcinoma sgc-7901 cells

NSC126188, a piperazine alkyl derivative, induces apoptosis via upregulation of RhoB in HeLa cells

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A novel benzimidazole analogue inhibits the hypoxia-inducible factor (HIF)-1 pathway

Cited by 52 publications

References 33 publications

Pantoprazole inhibits human gastric adenocarcinoma SGC-7901 cells by downregulating the expression of pyruvate kinase M2

Pantoprazole inhibits human gastric adenocarcinoma SGC-7901 cells by downregulating the expression of pyruvate kinase M2

Effects of pantoprazole as a HIF-1α inhibitor on human gastric adenocarcinoma sgc-7901 cells

NSC126188, a piperazine alkyl derivative, induces apoptosis via upregulation of RhoB in HeLa cells

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Effects of pantoprazole as a HIF-1α inhibitor on human gastric adenocarcinoma sgc-7901 cells