Non-Photoinduced Biological Properties of Verteporfin

Gibault, Floriane; Corvaisier, Matthieu; Bailly, Fabrice; Huet, Guillemette; Melnyk, Patricia; Cotelle, Philippe

doi:10.2174/0929867323666160316125048

Cited by 87 publications

(88 citation statements)

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“…We observed that the inhibition of EGFR pathway by VP is comparable to the mechanism of action of Lapatinib (Figure 6D). It has been previously reported that VP exhibited in vivo selectivity for killing tumor cells in part by impairing the global clearance of high-molecular weight oligomerzed proteins, particularly p62 (a sequestrome involved in autophagy) and Stat3 [29, 30]. However, in our studies, we observed that VP is able to induce sequestration in p62 alone, but not in Stat3 (Supplementary Figure 5).…”

Section: Resultscontrasting

confidence: 65%

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Verteporfin exhibits YAP-independent anti-proliferative and cytotoxic effects in endometrial cancer cells

et al. 2017

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Endometrial Carcinoma (EMCA) is the most common gynecologic malignancy and the fourth most common malignancy in women in the United States. Yes-associated protein (YAP) is a potent transcription coactivator acting via binding to the TEAD transcription factor, and plays a critical role in organ size regulation. Verteporfin (VP), a benzoporphyrin derivative, was identified as an inhibitor of YAP-TEAD interaction. We investigated the therapeutic efficacy and mechanism of VP in EMCA. The efficacy of VP on cell viability, cytotoxicity and invasion was assayed in EMCA cell lines. An organoid model system was also developed to test the effect of VP on apoptotic markers in an in vitro model system. Treatment with VP resulted in a decrease in cell viability, invasion and an increase in cytotoxicity of EMCA cells. These effects occurred as early as 15 minutes following treatment. Similarly, VP treatment versus vehicle control increased apoptosis in human organoid model systems. Quantitative RT-PCR, cDNA based RTPCR array analysis and western blotting were performed to investigate the mechanism of VP action. The cytotoxic and anti-proliferative effects appeared to be independent of its effect on YAP. Our results suggest that VP is a promising chemotherapeutic agent for the treatment of endometrial cancer.

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Section: Resultscontrasting

confidence: 65%

“…The rapid cytotoxic effect of YAP in EMCA cells described here appears to be independent of its inhibition of YAP. YAP independent effects of VP have been previously described [29, 31]. Zhang et al described the efficacy of VP in a colorectal model that was independent of YAP inhibition [31].…”

Section: Discussionmentioning

confidence: 99%

Verteporfin exhibits YAP-independent anti-proliferative and cytotoxic effects in endometrial cancer cells

et al. 2017

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“…Verteporfin is a YAP1-TEAD complex inhibitor that can inhibit the transcriptional activity of the YAP1-TEAD complex by preventing YAP1 and TEAD interaction [23–25]. To investigate whether inhibiting YAP1-TEAD activity affects ABCG2 in A549 and H460 cell lines, we treated the cells with serial concentration dilutions of verteporfin in 96 wells to measure the IC 50 (the drug concentration that kills 50% of cells) for A549 and H460 cells and determined the concentration for the SP assay.…”

Section: Resultsmentioning

confidence: 99%

“…The mechanism for YAP reduction by verteporfin is through upregulation of 14-3-3σ, which sequesters YAP1 in the cytoplasm and leads to YAP1 degradation [41]. However, verteporfin can act as an autophagosome inhibitor by promoting oligomerization of p62 and inhibit colon cancer progression independently of YAP1 [25, 42]. Hence, more specific inhibitors for YAP1/TEAD are needed for future study and clinical application.…”

Section: Discussionmentioning

confidence: 99%

YAP1 regulates ABCG2 and cancer cell side population in human lung cancer cells

et al. 2016

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A small population of cancer cells called cancer-initiating cells or cancer stem cells (CSCs) are involved in drug resistance, metastasis, and cancer relapse. Finding pathways that regulate CSC is very important for clinical therapy. ATP-binding cassette sub-family G member 2 (ABCG2) plays a role in side population (SP) cell formation and contributes to chemotherapy resistance in common forms of cancer. Yes-associated protein 1 (YAP1) is a major transcriptional effector of the Hippo pathway, which plays important roles in organ size control and tumorigenesis. In this study, we found ABCG2 and YAP1 were both overexpressed in lung cancer SP cells. Disruption of YAP1 expression by siRNA attenuated the expression of ABCG2 transcript and significantly reduced the percentage of SP cells and sphere formation in lung cancer cells. Overexpression of YAP1 in lung cancers led to an increase in ABCG2 expression and increased the percentage of SP cells. However, overexpression of YAP1 in purified non-SP cells did not increase ABCG2 expression and the percentage of SP cells, which may be due to the inhibition of YAP activity through phosphorylation. YAP1 directly transcriptionally regulated ABCG2 by binding to the promoter of ABCG2. Moreover, the YAP1 inhibitor verteporfin and YAP1 siRNA downregulated ABCG2 level through inhibition of YAP1 in lung cancer cells and sensitized them to the chemotherapy drug doxorubicin. Our study adds a new function for YAP1 that may be relevant to drug resistance and cancer therapy through regulation of ABCG2 and side population cell formation in lung cancer.

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“…First, although nude mice xenografts are considered to be generally used models in cancer research,36 they are not ideal to mimic the human disease due to the immunodeficient environment. Second, VP has a low half-life ( t 1/2 ~3 hours) because of rapid excretion in the feces, which may not be suitable for long-term treatments 37. Further investigation about the real efficacy of VP, its pharmacokinetics, or the appropriate administration route should be done.…”

Section: Discussionmentioning

confidence: 99%

Verteporfin, a suppressor of YAP–TEAD complex, presents promising antitumor properties on ovarian cancer

Feng¹,

Gou²,

Jia³

et al. 2016

OTT

103

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Yes-associated protein (YAP) is a key transcriptional coactivator of Hippo pathway and has been shown to be an oncoprotein in ovarian cancer (OC). Verteporfin (VP), clinically used in photodynamic therapy for neovascular macular degeneration, has been recently proven to be a suppressor of YAP–TEAD complex and has shown potential in anticancer treatment. In this study, we aimed to explore the potential effect of VP in the treatment of OC. Our results showed that VP led to inhibition of proliferation in a time- and dose-dependent manner and to the suppression of migratory and invasive capacities of OC cells. Western blot and real-time polymerase chain reaction demonstrated that VP induced YAP cytoplasmic retention and deregulated inducible YAP and CCNs in OC cells. In vivo, VP exerted a significant effect on tumor growth in OVCAR8 xenograft mice, resulting in tumor nodules with lower average weight and reduced volume of gross ascites. In addition, VP treatment remarkably upregulated cytoplasmic YAP and phosphorylation YAP and downregulated CCN1 and CCN2, but exerted little effect on YAP-upstream components in Hippo pathway. In conclusion, our results suggested that VP may be a promising agent for OC, acting by suppressing YAP–TEAD complex.

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Non-Photoinduced Biological Properties of Verteporfin

Abstract: VP is a multi-target drug interacting with several proteins implicated in major cellular processes. Although this does not impact its clinical use, VP does not seem to be the ideal drug for pharmacological inhibitions of YAP/TEAD.

Cited by 87 publications

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Verteporfin exhibits YAP-independent anti-proliferative and cytotoxic effects in endometrial cancer cells

Verteporfin exhibits YAP-independent anti-proliferative and cytotoxic effects in endometrial cancer cells

YAP1 regulates ABCG2 and cancer cell side population in human lung cancer cells

Verteporfin, a suppressor of YAP–TEAD complex, presents promising antitumor properties on ovarian cancer

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Non-Photoinduced Biological Properties of Verteporfin

Abstract: VP is a multi-target drug interacting with several proteins implicated in major cellular processes. Although this does not impact its clinical use, VP does not seem to be the ideal drug for pharmacological inhibitions of YAP/TEAD.

Cited by 87 publications

References 0 publications

Verteporfin exhibits YAP-independent anti-proliferative and cytotoxic effects in endometrial cancer cells

Verteporfin exhibits YAP-independent anti-proliferative and cytotoxic effects in endometrial cancer cells

YAP1 regulates ABCG2 and cancer cell side population in human lung cancer cells

Verteporfin, a suppressor of YAP&ndash;TEAD complex, presents promising antitumor properties on ovarian cancer

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Verteporfin, a suppressor of YAP–TEAD complex, presents promising antitumor properties on ovarian cancer