Differential gene expression induced by Verteporfin in endometrial cancer cells

Bang, Lisa; Dasari, Venkata Ramesh; Kim, Dokyoon; Gogoi, Radhika

doi:10.1038/s41598-019-40495-9

Cited by 8 publications

(10 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results also confirm that inhibition of migration and clonogenic capacity is induced by VP treatments. Supporting our previous studies with EMCA [24,25], VP inhibits cell cycle proteins in OVCA, suggesting the mechanism of inhibition of cell proliferation by cell cycle inhibition. Taken together, we suggest that VP has a role in initial therapy since it improves efficacy of CDDP and that it has a role in drug resistance because it overcomes platinum resistance.…”

Section: Discussionsupporting

confidence: 85%

“…Previously, we showed that VP inhibits expression of cell cycle genes in vitro and in vivo in EMCA [24,25]. Similar to these results, VP inhibits cell cycle gene expression in OVCA also (Fig.…”

Section: Efficiency Of Vp In Inhibiting Metabolic Functions Of Ovca Csupporting

confidence: 86%

“…Since the identification of VP as a YAP/TEAD inhibitor, several in vitro and in vivo studies have revealed the potential of VP for treatment of different cancers [20][21][22][23]. We tested the efficacy of VP treatment in Type 1 endometrial cancer (EMCA) cells (HEC-1-A and HEC-1-B) and observed cytotoxic and anti-proliferative effects [24] and analyzed RNAseq data to investigate the comprehensive transcriptomic landscape of VP treated Type 1 EMCA cells [25]. We also observed that subcutaneous tumors of EMCA in nude mice were regressed after VP treatment by inhibiting cell cycle pathway proteins.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Synergistic enhancement of efficacy of platinum drugs with verteporfin in ovarian cancer cells

2020

Self Cite

View full text Add to dashboard Cite

Background: Epithelial ovarian cancers (EOCs) comprises the majority of malignant ovarian neoplasms. Combination treatment with chemotherapeutic agents seems to be a promising strategy in ovarian cancer (OVCA) patients in order to overcome drug resistance. In this in vitro study, we investigated the therapeutic efficacy of verteporfin (VP) alone and in combination with cisplatin (CDDP), carboplatin (CP) and paclitaxel (Taxol). The main objectives of this study are to determine the nature of interactions between VP and CDDP/CP/Taxol and to understand the mechanism of action of VP in OVCA cells. Methods: The efficacy of VP on cell proliferation, cytotoxicity, invasion and clonogenic capacity was assayed in CDDP-sensitive (COV504, OV-90) and CDDP-resistant (A2780Cis) cell lines. The cytotoxic effects of drugs either alone or in combination were evaluated using MTT assay and Cell Viability Blue assay. The effects of drugs on the metabolic functions were studied using matrigel invasion assay and clonogenic assay. Immunoblot analysis was carried out to investigate changes in YAP and cell cycle genes. Changes in the cytokines due to drug treatments were analyzed using a cytokine array. Results: Treatment with VP inhibited cell proliferation, invasion and increased cytotoxicity of OVCA cells. We observed that VP chemosensitized CDDP-resistant cells, even at lower doses. When added either in constant or non-constant ratios, VP produced synergistic effects in combination with CDDP/CP/Taxol. A cytokine array identified upregulation of cytokines in OVCA cells that were inhibited by VP treatment. Conclusions: Either in cisplatin-resistant cell lines or cisplatin-sensitive cell lines, VP proves to be more efficient in inhibiting cell proliferation and inducing cytotoxicity. Our results suggest that novel combinations of VP with CDDP or CP or Taxol might be an attractive therapeutic strategy to enhance OVCA chemosensitivity. The fact that lower doses of VP are effective in chemosensitizing the CDDP-resistant cells, might ultimately lead to the development of an innovative combination therapy for the treatment of OVCA patients.

show abstract

Section: Discussionsupporting

confidence: 85%

Section: Efficiency Of Vp In Inhibiting Metabolic Functions Of Ovca Csupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synergistic enhancement of efficacy of platinum drugs with verteporfin in ovarian cancer cells

2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Overexpression of BUB1B has been demonstrated to be strongly associated with advanced tumor stage, poor OS rate and high tumor recurrence rate in various tumors, including pancreatic ductal adenocarcinoma, gastric cancer, bladder cancer and liver cancer ( 53 – 56 ). An in vitro study on verteporfin-treated type 1 EC cell lines (HEC-1-B cells) demonstrated that BUB1B regulates the progression of the mitotic checkpoint ( 57 ). By contrast, lower levels of BUB1B have been associated with a poor OS rate in colon adenocarcinoma ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of a five‑gene signature for predicting the progression and prognosis of stage I endometrial carcinoma

et al. 2020

Oncol Lett

View full text Add to dashboard Cite

Uterine corpus endometrial carcinoma (UCEC) is often diagnosed at an early clinical stage based on abnormal vaginal bleeding. However, the prognosis of UCEC is poor. The present study was conducted to identify novel tumor grade-related genes with the potential to predict the prognosis and progression of UCEC. A total of three gene expression microarray datasets were downloaded from the Gene Expression Omnibus database, and one RNA-sequencing dataset with corresponding clinical information of patients with UCEC was obtained from The Cancer Genome Atlas database. In summary, 1,447 differentially expressed genes (DEGs) were identified between endometrial cancerous tissues and normal endometrial tissues. Weighted gene co-expression network analysis was performed to assess the associations between DEGs and clinical traits. In total, five genes were found to be highly associated with the tumorigenesis and prognosis of UCEC. Among them, BUB1 mitotic checkpoint serine/threonine kinase B, cyclin B1, cell-division cycle protein 20 and non-SMC condensing I complex subunit G were involved in cell cycle regulation pathways, and DLG-associated protein 5 was involved in the Notch receptor 3 signaling pathway based on functional enrichment analyses. Of the five genes, four were highly expressed in endometrial cancerous tissues compared with normal endometrial tissues at the protein level. In addition, the higher expression of these genes predicted a higher tumor grade and worse overall survival. In conclusion, the present study revealed a 5-gene signature that can be used to predict the progression of UCEC.

show abstract

“…YAP transcriptionally activates IL-6, and stimulate IL-11 by up-regulating p65. Targeted inhibition of YAP by VP inhibited the binding between YAP and the IL-6 promoter, and downregulated IL-6 and IL-11 in endometrial cancer cells, resulting in lower proliferation rates ( Wang J. et al, 2019 ), increased sensitivity to adriamycin, and 45.36% decrease in tumor weight in the treated mice ( Bang et al, 2019 ).…”

Section: The Role Of Non-photoactivated Verteporfin In Tumorsmentioning

confidence: 99%

The Role of Photoactivated and Non-Photoactivated Verteporfin on Tumor

Wei

2020

Front. Pharmacol.

View full text Add to dashboard Cite

Verteporfin (VP) has long been clinically used to treat age-related macular degeneration (AMD) through photodynamic therapy (PDT). Recent studies have reported a significant anti-tumor effect of VP as well. Yes-associated protein (YAP) is a pro-tumorigenic factor that is aberrantly expressed in various cancers and is a central effector of the Hippo signaling pathway that regulates organ size and tumorigenesis. VP can inhibit YAP without photoactivation, along with suppressing autophagy, and downregulating germinal center kinase-like kinase (GLK) and STE20/SPS1-related proline/alanine-rich kinase (SPAK). In addition, VP can induce mitochondrial damage and increase the production of reactive oxygen species (ROS) upon photoactivation, and is an effective photosensitizer (PS) in anti-tumor PDT. We have reviewed the direct and adjuvant therapeutic action of VP as a PS, and its YAP/TEA domain (TEAD)-dependent and independent pharmacological effects in the absence of light activation against cancer cells and solid tumors. Based on the present evidence, VP may be repositioned as a promising anti-cancer chemotherapeutic and adjuvant drug.

show abstract

Differential gene expression induced by Verteporfin in endometrial cancer cells

Cited by 8 publications

References 56 publications

Synergistic enhancement of efficacy of platinum drugs with verteporfin in ovarian cancer cells

Synergistic enhancement of efficacy of platinum drugs with verteporfin in ovarian cancer cells

Identification of a five‑gene signature for predicting the progression and prognosis of stage I endometrial carcinoma

The Role of Photoactivated and Non-Photoactivated Verteporfin on Tumor

Contact Info

Product

Resources

About