AccScience Publishing / GPD / Volume 2 / Issue 2 / DOI: 10.36922/gpd.0658

Verteporfin induces YAP-dependent cell cycle arrest and caspase-mediated cellular apoptosis in triple-negative breast cancer cells

Sulfath Thottungal Parambil1 Gisha Rose Antony1 Ajeesh Babu Littleflower1 Lakshmi Subhadradevi1*
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1 Laboratory of Molecular Medicine, Division of Cancer Research, Regional Cancer Centre (Research Centre, University of Kerala), Thiruvananthapuram, Kerala, India
Submitted: 19 April 2023 | Accepted: 26 June 2023 | Published: 7 July 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( )

Triple-negative breast cancer (TNBC) subtype endows distinctive biological features, including aberrant proliferation, and deducing the molecular mechanism harmonizing the TNBC characteristics is crucial for a greater understanding and prognosis of the disease. The aim of the present study was to analyze the anti-tumorigenic effects of verteporfin (VP) in TNBC in vitro. We evaluated the tumorigenic properties of TNBC cells on VP treatment to assess the cell viability, apoptosis, cell cycle, cell survival, and protein/mRNA expressions in MDA-MB-231 and SUM-159 breast cancer cells. Transient silencing of yes-associated protein (YAP) was performed to validate the data. TNBC cells exhibited a comparatively higher active YAP downstream signaling, and VP resulted in the nuclear exclusion of YAP to a significant extent. VP inhibits the proliferation of TNBC cells by altering cyclin-dependent kinase inhibitors, thereby rendering cellular arrest at the G0/G1 phase. In a dose-dependent manner, VP induces the apoptotic machinery in TNBC cells. Moreover, transient silencing of YAP in TNBC cells exhibited a similar pattern of antiproliferative effects. Elevated YAP nuclear activity and downstream signaling in TNBC are associated with sustaining the proliferative capacity of the cells by inhibiting cellular apoptosis. VP induces antiproliferative effects on TNBC through cytoplasmic retention of YAP. Consequently, cells rewire the course of the cell cycle and stimulate cellular death. We suggest YAP signaling as a prerequisite for TNBC cell progression, and VP without light activation exerts anti-tumorigenic effects on TNBC cells.

Triple-negative breast cancer
Yes-associated protein
Cell cycle
Hippo signaling
Fellowship grant from ICMR
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Conflict of interest
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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Gene & Protein in Disease, Electronic ISSN: 2811-003X Published by AccScience Publishing