Research Article
Viola tricolor Induces Apoptosis in Cancer Cells and Exhibits
Antiangiogenic Activity on Chicken Chorioallantoic Membrane
Hamid Reza Sadeghnia,
1,2,3
Taghi Ghorbani Hesari,
4
Seyed Mohsen Mortazavian,
3
Seyed Hadi Mousavi,
2,3
Zahra Tayarani-Najaran,
4
and Ahmad Ghorbani
2
1
Neurocognitive Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran
2
Pharmacological Research Center of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences,
Mashhad 9177948564, Iran
3
Department of Pharmacology, School of Medicine, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran
4
Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences,
Mashhad 917751365, Iran
Correspondence should be addressed to Ahmad Ghorbani; ghorbania@mums.ac.ir
Received 27 February 2014; Revised 17 June 2014; Accepted 4 August 2014; Published 28 August 2014
Academic Editor: Adair Santos
Copyright © 2014 Hamid Reza Sadeghnia et al. his is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
In the present study, the cytotoxic and apoptogenic properties of hydroalcoholic extract and ethyl acetate (EtOAc), n-butanol, and
water fractions (0–800 g/mL) of Viola tricolor were investigated in Neuro2a mouse neuroblastoma and MCF-7 human breast
cancer cells. In addition, antiangiogenic efect of EtOAc fraction was evaluated on chicken chorioallantoic membrane (CAM). he
quality of EtOAc fraction was also characterized using high performance liquid chromatography (HPLC) ingerprint. Cytotoxicity
assay revealed that EtOAc fraction was the most potent among all fractions with maximal efect on MCF-7 and minimal toxicity
against normal murine ibroblast L929 cells. Apoptosis induction by EtOAc fraction was conirmed by increased sub-G1 peak of
propidium iodide (PI) stained cells. his fraction triggered the apoptotic pathway by increased Bax/Bcl-2 ratio and cleaved caspase-
3 level. Moreover, treatment with EtOAc fraction signiicantly decreased the diameter of vessels on CAM, while the number of newly
formed blood vessels was not suppressed signiicantly. Analysis of quality of EtOAc fraction using HPLC ingerprint showed six
major peaks with diferent retention times. he results of the present study suggest that V. tricolor has potential anticancer property
by inducing apoptosis and inhibiting angiogenesis.
1. Introduction
Cancer is a devastating disease with tremendous negative
implications at the personal, health care, economical, and
social levels. It igures among the leading causes of death
worldwide, accounting for 8.2 million deaths in 2012 [1].
Excluding skin cancers, breast cancer is the most com-
mon malignancy and the second leading cause of cancer
death among women [2]. Breast cancer is a heterogeneous
disease encompassing multiple subgroups with difering
molecular signatures, prognoses, and responses to therapies.
Although, current treatment options for breast cancer are
moving toward nontoxic, potent targeted therapies that can
be tailored to an individual patient’s tumor, the development
of resistance to all of these therapies is an ongoing challenge
[3].
Neuroblastoma accounts for disproportionate morbidity
and mortality among the cancers of childhood. It is a complex
and heterogeneous disease and, despite recent advances, 50 to
60% of patients with high-risk neuroblastoma have a relapse,
and to date there are no salvage treatment regimens known
to be curative [4].
Phytochemicals from herbs are becoming increasingly
important sources of anticancer drugs or compounds for
cancer chemoprevention or adjuvant chemotherapy [5].
Recently, some chemopreventive extracts of herbs have
been shown to be antitumorigenic [6, 7]. he anticancer
efects have been shown to be mediated through inhibiting
Hindawi Publishing Corporation
BioMed Research International
Volume 2014, Article ID 625792, 8 pages
http://dx.doi.org/10.1155/2014/625792