Page 84 - GPD-2-2

Gene & Protein in Disease

ORIGINAL RESEARCH ARTICLE
Verteporfin induces YAP-dependent cell cycle

arrest and caspase-mediated cellular apoptosis
in triple-negative breast cancer cells

Sulfath Thottungal Parambil, Gisha Rose Antony, Ajeesh Babu Littleflower,
and Lakshmi Subhadradevi*
Laboratory of Molecular Medicine, Division of Cancer Research, Regional Cancer Centre (Research
Centre, University of Kerala), Thiruvananthapuram, Kerala, India

Abstract
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,
*Corresponding author: VP induces the apoptotic machinery in TNBC cells. Moreover, transient silencing of
Lakshmi Subhadradevi YAP in TNBC cells exhibited a similar pattern of antiproliferative effects. Elevated YAP
(rcc.lakshmi@gmail.com)
nuclear activity and downstream signaling in TNBC are associated with sustaining
Citation: Parambil ST, Antony GR, the proliferative capacity of the cells by inhibiting cellular apoptosis. VP induces
Littleflower AB, et al., 2023,
Verteporfin induces YAP-dependent antiproliferative effects on TNBC through cytoplasmic retention of YAP. Consequently,
cell cycle arrest and caspase- cells rewire the course of the cell cycle and stimulate cellular death. We suggest YAP
mediated cellular apoptosis in triple- signaling as a prerequisite for TNBC cell progression, and VP without light activation
negative breast cancer cells. Gene
Protein Dis, 2(2): 0658. exerts anti-tumorigenic effects on TNBC cells.
https://doi.org/10.36922/gpd.0658
Received: April 19, 2023 Keywords: Verteporfin; Triple-negative breast cancer; Yes-associated protein; Cell cycle;
Accepted: June 26, 2023
Published Online: July 7, 2023 Hippo signaling
Copyright: © 2023 Author(s).
This is an Open Access article
distributed under the terms of the
Creative Commons Attribution 1. Introduction
License, permitting distribution,
and reproduction in any medium, The groundbreaking effort to unravel molecular portraits of breast cancer by Perou
provided the original work is et al. has shed considerable light on the possibility of various classes of breast cancer .
[1]
properly cited. The absence of hormone receptors (estrogen receptors and progesterone receptors) and
Publisher’s Note: AccScience lack of overexpressed human epidermal growth factor receptor-2 (HER-2) in triple-
Publishing remains neutral with negative breast cancer (TNBC) is highly unfavorable for the patients as the hormone
regard to jurisdictional claims in
published maps and institutional therapy and monoclonal antibody administration will not applicable like the hormone-
[2]
affiliations. receptor-positive breast cancer subtypes . TNBC incidences comprise 15 – 20% of all

Volume 2 Issue 2 (2023) 1 https://doi.org/10.36922/gpd.0658