Verteporfin inhibits cell proliferation and induces apoptosis in different subtypes of breast cancer cell lines without light activation

Wei, Chunli; Li, Xiangqi

doi:10.1186/s12885-020-07555-0

Cited by 37 publications

(31 citation statements)

References 34 publications

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“…YAP not only activates ERK and AXL signaling, but also induces epithelial–mesenchymal transition (EMT) against EGFR-TKI treatment [ 16 ]. Several studies have shown that YAP inhibition can overcome resistance to chemotherapy [ 39 , 40 , 41 , 42 ]. For example, the combined treatment of EGFR-TKI with YAP inhibitors suppresses EGFR-TKI resistance [ 16 ].…”

Section: The Role Of Yap In Chemo-resistance and Metastasismentioning

confidence: 99%

New Insights into the Clinical Implications of Yes-Associated Protein in Lung Cancer: Roles in Drug Resistance, Tumor Immunity, Autophagy, and Organoid Development

Yoo

Park

Kim

et al. 2021

Cancers

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Despite significant innovations in lung cancer treatment, such as targeted therapy and immunotherapy, lung cancer is still the principal cause of cancer-associated death. Novel strategies to overcome drug resistance and inhibit metastasis in cancer are urgently needed. The Hippo pathway and its effector, Yes-associated protein (YAP), play crucial roles in lung development and alveolar differentiation. YAP is known to mediate mechanotransduction, an important process in lung homeostasis and fibrosis. In lung cancer, YAP promotes metastasis and confers resistance against chemotherapeutic drugs and targeted agents. Recent studies revealed that YAP directly controls the expression of programmed death-ligand 1 (PD-L1) and modulates the tumor microenvironment (TME). YAP not only has a profound relationship with autophagy in lung cancer but also controls alveolar differentiation, and is responsible for tubular structure formation in lung organoids. In this review, we discuss the various roles and clinical implications of YAP in lung cancer and propose that targeting YAP can be a promising strategy for treating lung cancer.

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Section: The Role Of Yap In Chemo-resistance and Metastasismentioning

confidence: 99%

New Insights into the Clinical Implications of Yes-Associated Protein in Lung Cancer: Roles in Drug Resistance, Tumor Immunity, Autophagy, and Organoid Development

Yoo

Park

Kim

et al. 2021

Cancers

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Section: Resultsmentioning

confidence: 99%

“…This drug is used as a photosensitizer for photodynamic therapy to eliminate abnormal blood vessels in the eye, which are associated with conditions such as the wet form of macular degeneration [19]. Recently, verteporfin has also been shown to inhibit the function of the oncogene YAP1 through regulation of YAP1 SUMOylation, proposing verteporfin for clinical use to treat breast cancer [20], as well as myeloma [21]. The process of identifying the most active individual compounds was then repeated for plate 10 (Figure 2D,E), resulting in the identification of compound P10G08 as the most potent inhibitor of the pUL50-pUL53 interaction (IC 50 = 38 nM, Figure 2F).…”

Section: Identification Of Hcmv Core Nec Inhibitors From the Prestwick Chemical Library ®mentioning

confidence: 99%

Exploring the Human Cytomegalovirus Core Nuclear Egress Complex as a Novel Antiviral Target: A New Type of Small Molecule Inhibitors

Alkhashrom

Kicuntod

Häge

et al. 2021

Viruses

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Nuclear egress is an essential process in the replication of human cytomegalovirus (HCMV), as it enables the migration of newly formed viral capsids from the nucleus into the cytoplasm. Inhibition of the HCMV core nuclear egress complex (core NEC), composed of viral proteins pUL50 and pUL53, has been proposed as a potential new target for the treatment of HCMV infection and disease. Here, we present a new type of small molecule inhibitors of HCMV core NEC formation, which inhibit the pUL50-pUL53 interaction at nanomolar concentrations. These inhibitors, i.e., verteporfin and merbromin, were identified through the screening of the Prestwick Chemical Library® of approved drug compounds. The inhibitory effect of merbromin is both compound- and target-specific, as no inhibition was seen for other mercury-organic compounds. Furthermore, merbromin does not inhibit an unrelated protein–protein interaction either. More importantly, merbromin was found to inhibit HCMV infection of cells in three different assays, as well as to disrupt HCMV NEC nuclear rim formation. Thus, while not being an ideal drug candidate by itself, merbromin may serve as a blueprint for small molecules with high HCMV core NEC inhibitory potential, as candidates for novel anti-herpesviral drugs.

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“…Effects of paclitaxel on apoptosis and the apoptosis signaling pathways in PC9 cells. Chemotherapy drugs can inhibit cell proliferation and induce apoptosis in human cancer cells (36)(37)(38). To confirm that the cell death caused by paclitaxel was indeed apoptosis, we performed Annexin V and PI staining for a flow cytometry analysis.…”

Section: Effects Of Paclitaxel On Mmpmentioning

confidence: 99%

Paclitaxel Impedes EGFR-mutated PC9 Cell GrowthviaReactive Oxygen Species-mediated DNA Damage and EGFR/PI3K/AKT/mTOR Signaling Pathway Suppression

Mohiuddin

Kondo

2021

Cancer Genomics Proteomics

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Background/Aim: Paclitaxel is used as a first-line and subsequent therapy for the treatment of various cancers. However, the function and mechanisms of action of paclitaxel in non-small-cell lung cancer (NSCLC) remain unknown. In this study, the molecular mechanism underlying the anticancer activity of paclitaxel was investigated in vitro in a human NSCLC cell line carrying the EGFR exon 19 deletion (PC9). Materials and Methods: PC9 cells were treated with paclitaxel and then evaluated with a cell viability assay, DAPI staining, Giemsa staining, apoptosis assay, reactive oxygen species (ROS) assay, terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and Western blotting. Results: Paclitaxel markedly decreased the viability of PC9 cells and induced morphological signs of apoptosis. The apoptotic effects of paclitaxel were observed through caspase cascade activation, along with ROS generation and loss of mitochondrial membrane potential (MMP). Furthermore, paclitaxel induced ROS-mediated DNA damage that triggered the activation of the extrinsic pathway of apoptosis via the up-regulation of death receptor (DR5) and caspase-8 activation. In addition, we found that paclitaxel effectively suppressed the EGFR/PI3K/AKT/mTOR signaling pathway to impede PC9 cell growth. Paclitaxel induced cell cycle arrest at the G1 phase in response to DNA damage, in association with the suppression of CDC25A, Cdk2 and Cyclin E1 protein expression. Conclusion: Paclitaxel showed anticancer effects against NSCLC by activating extrinsic and intrinsic apoptotic pathways through enhancing ROS generation, inducing cell cycle arrest, and suppressing EGFR/PI3K/AKT/mTOR signaling pathway.

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Verteporfin inhibits cell proliferation and induces apoptosis in different subtypes of breast cancer cell lines without light activation

Cited by 37 publications

References 34 publications

New Insights into the Clinical Implications of Yes-Associated Protein in Lung Cancer: Roles in Drug Resistance, Tumor Immunity, Autophagy, and Organoid Development

New Insights into the Clinical Implications of Yes-Associated Protein in Lung Cancer: Roles in Drug Resistance, Tumor Immunity, Autophagy, and Organoid Development

Exploring the Human Cytomegalovirus Core Nuclear Egress Complex as a Novel Antiviral Target: A New Type of Small Molecule Inhibitors

Paclitaxel Impedes EGFR-mutated PC9 Cell GrowthviaReactive Oxygen Species-mediated DNA Damage and EGFR/PI3K/AKT/mTOR Signaling Pathway Suppression

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