Inhibition of JNK-Mediated Autophagy Promotes Proscillaridin A- Induced Apoptosis via ROS Generation, Intracellular Ca+2 Oscillation and Inhibiting STAT3 Signaling in Breast Cancer Cells

Frontiers in Pharmacology
Muhammad Zubair SaleemTonghui Ma


Breast cancer is the most heterogenous cancer type among women across the world. Despite concerted efforts, breast cancer management is still unsatisfactory. Interplay between apoptosis and autophagy is an imperative factor in categorizing therapeutics for cancer treatment. Proscillaridin A (PSD-A), a well-known cardiac glycoside used for cardiac arrest and arrythmias, has been unveiled in many cancer types but the underlying mechanism for apoptosis and autophagy in breast cancer is not fully understood. In our study, PSD-A restricted cell growth, inhibited STAT3 activation and induced apoptosis and autophagy in breast cancer cells via ROS generation and Ca+2 oscillation. Pretreatment of NAC and BAPTA-AM restored PSD-A induced cellular events in breast cancer cells. PSD-A induced apoptosis via DNA fragmentation, caspase-cascade activation, PARP cleavage, mitochondrial dysfunction, Bax/Bcl-2 proteins modulation and ER chaperone GRP78 inhibition along with decreased phosphorylation of ERK1/2. Inhibition of STAT3 activation was found to be associated with decreased phosphorylation of SRC. Moreover, PSD-A induced events of autophagy i.e. conversion of LC3-I to LC3-II, and Atg3 expression via JNK activation and decreased mTOR and AK...Continue Reading


Jun 20, 2001·Nature Reviews. Molecular Cell Biology·M J BerridgeM D Bootman
Sep 9, 2005·Nature Reviews. Cancer·Yasuko KondoSeiji Kondo
Oct 13, 2006·Molecular and Cellular Biology·Maiko OgataKazunori Imaizumi
Apr 26, 2007·Autophagy·Maria Høyer-Hansen, Marja Jäättelä
Jun 4, 2008·Biological & Pharmaceutical Bulletin·Katarzyna WinnickaArkadiusz Surazyński
Oct 25, 2008·Nature Reviews. Drug Discovery·Ioannis Prassas, Eleftherios P Diamandis
Apr 20, 2012·Journal of Neuroscience Research·Jezabel Rodríguez-BlancoCarmen Rodriguez
Jun 16, 2012·CA: a Cancer Journal for Clinicians·Rebecca SiegelElizabeth Ward
Jul 4, 2012·The International Journal of Biochemistry & Cell Biology·Yan WangZhen Wang
Sep 20, 2012·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Reina HaqueMichael F Press
Dec 20, 2012·The Journal of Biological Chemistry·Celia Garcia-PrietoPeng Huang
Jun 12, 2013·Investigational New Drugs·M SlingerlandH Gelderblom
Dec 19, 2013·Genes & Cancer·Cathy Tournier
Jun 5, 2014·BioMed Research International·José Manuel Calderón-MontañoMiguel López-Lázaro
Dec 22, 2014·Photodiagnosis and Photodynamic Therapy·Qin XueQuanhong Liu
Jan 9, 2016·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Jul 20, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Elaheh NooshinfarMohammad Esmaeil Akbari
Aug 30, 2016·Seminars in Cell & Developmental Biology·Rachel E EllsworthDarrell L Ellsworth
Jan 26, 2018·Journal of Ethnopharmacology·Prachi KariaShri S P Rathod
Feb 24, 2018·Cancer Letters·Mohammad Amin MoosaviAtanas G Atanasov
Apr 1, 2018·Chemico-biological Interactions·Guang YangShaopeng Wang
May 6, 2019·Journal of Experimental & Clinical Cancer Research : CR·Xihong LiuWei Gao

Related Concepts

MCF-7 Cells
Cancer Stem Cells
Cardiac Arrest
biological signaling
LC3 protein, rat
Cancer Treatment
Breast Cancer Cell
FRAP1 protein, human

Related Feeds

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms


Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.


Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Breast Cancer: Therapeutic Approaches

Several different therapeutic approaches are used to treat breast cancer. These include chemotherapy, hormonal therapy, targeted therapy, and Immunotherapy. Discover the latest research on breast cancer therapeutic approaches here.

Atrial Fibrillation

Atrial fibrillation is a common arrhythmia that is associated with substantial morbidity and mortality, particularly due to stroke and thromboembolism. Here is the latest research.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Related Papers

The Journal of Clinical Ethics
S M Weiss
The Hastings Center Report
Fenella RouseE L McCloskey
The Bulletin of the American Academy of Psychiatry and the Law
S K Hoge
© 2020 Meta ULC. All rights reserved