4,6,4′-Trimethylangelicin Photoactivated by Blue Light Might Represent an Interesting Option for Photochemotherapy of Non-Invasive Bladder Carcinoma: An In Vitro Study on T24 Cells

Sturaro, Giulio; Tasso, Alessia; Menilli, Luca; Di Liddo, Rosa; Miolo, Giorgia; Conconi, Maria Teresa

doi:10.3390/biom11020158

Open AccessFeature PaperArticle

4,6,4′-Trimethylangelicin Photoactivated by Blue Light Might Represent an Interesting Option for Photochemotherapy of Non-Invasive Bladder Carcinoma: An In Vitro Study on T24 Cells

by

Giulio Sturaro

,

Alessia Tasso

,

Luca Menilli

,

Rosa Di Liddo

,

Giorgia Miolo

^*,†

and

Maria Teresa Conconi

^†

Department of Pharmaceutical and Pharmacological Sciences, University of Padua, via Marzolo, 5, 35131 Padova, Italy

^*

Author to whom correspondence should be addressed.

^†

This author contributes equally to the work.

Biomolecules 2021, 11(2), 158; https://doi.org/10.3390/biom11020158

Submission received: 16 December 2020 / Revised: 14 January 2021 / Accepted: 21 January 2021 / Published: 25 January 2021

(This article belongs to the Collection Drug-Phototherapy)

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Abstract

Photodynamic therapy (PDT) is frequently used to treat non-muscle invasive bladder cancer due its low toxicity and high selectivity. Since recurrence often occurs, alternative approaches and/or designs of combined therapies to improve PDT effectiveness are needed. This work aimed to evaluate the cytotoxicity of 4,6,4′-trimethylangelicin (TMA) photoactivated by blue light (BL) on human bladder cancer T24 cells and investigate the mechanisms underlying its biological effects. TMA/BL exerted antiproliferative activity through the induction of apoptosis without genotoxicity, as demonstrated by the expression levels of phospho-H2AX, an indicator of DNA double-stranded breaks. It also modulated the Wnt canonical signal pathway by increasing the phospho-β-catenin and decreasing the nuclear levels of β-catenin. The inhibition of this pathway was due to the modulation of the GSK3β phosphorylation state (Tyr 216) that induces a proteasomal degradation of β-catenin. Indeed, a partial recovery of nuclear β-catenin expression and reduction of its phosphorylated form after treatment with LiCl were detected. As demonstrated by RT-PCR and cytofluorimetric analysis, TMA/BL also decreased the expression of CD44v6, a marker of cancer stem cells. Taken together, our data suggest that TMA photoactivated by BL may represent an interesting option for the photochemotherapy of noninvasive bladder carcinomas, since this treatment is able to inhibit key pathways for tumour growth and progression in the absence of genotoxic effects.

Keywords: bladder cancer; T24 cell line; 4,6,4′-trimethylangelicin; Wnt signalling pathway

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MDPI and ACS Style

Sturaro, G.; Tasso, A.; Menilli, L.; Di Liddo, R.; Miolo, G.; Conconi, M.T. 4,6,4′-Trimethylangelicin Photoactivated by Blue Light Might Represent an Interesting Option for Photochemotherapy of Non-Invasive Bladder Carcinoma: An In Vitro Study on T24 Cells. Biomolecules 2021, 11, 158. https://doi.org/10.3390/biom11020158

AMA Style

Sturaro G, Tasso A, Menilli L, Di Liddo R, Miolo G, Conconi MT. 4,6,4′-Trimethylangelicin Photoactivated by Blue Light Might Represent an Interesting Option for Photochemotherapy of Non-Invasive Bladder Carcinoma: An In Vitro Study on T24 Cells. Biomolecules. 2021; 11(2):158. https://doi.org/10.3390/biom11020158

Chicago/Turabian Style

Sturaro, Giulio, Alessia Tasso, Luca Menilli, Rosa Di Liddo, Giorgia Miolo, and Maria Teresa Conconi. 2021. "4,6,4′-Trimethylangelicin Photoactivated by Blue Light Might Represent an Interesting Option for Photochemotherapy of Non-Invasive Bladder Carcinoma: An In Vitro Study on T24 Cells" Biomolecules 11, no. 2: 158. https://doi.org/10.3390/biom11020158

APA Style

Sturaro, G., Tasso, A., Menilli, L., Di Liddo, R., Miolo, G., & Conconi, M. T. (2021). 4,6,4′-Trimethylangelicin Photoactivated by Blue Light Might Represent an Interesting Option for Photochemotherapy of Non-Invasive Bladder Carcinoma: An In Vitro Study on T24 Cells. Biomolecules, 11(2), 158. https://doi.org/10.3390/biom11020158

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4,6,4′-Trimethylangelicin Photoactivated by Blue Light Might Represent an Interesting Option for Photochemotherapy of Non-Invasive Bladder Carcinoma: An In Vitro Study on T24 Cells

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