Withaferin A health benefit and anti cancer agent
Withaferin A is present abundantly in Withania somnifera or ashwagandha, a well-known Indian medicinal plant which has been safely used for centuries in Indian Ayurvedic medicine for treatment of different ailments. You can purchase Ashwagandha supplement at this online store.
Withaferin A and cancer
Withaferin A exhibits significant activity against human breast cancer cells in
culture and in vivo.
Withaferin A induces apoptosis by activating p38
mitogen-activated protein kinase signaling cascade in leukemic cells of lymphoid
and myeloid origin through mitochondrial death cascade.
Apoptosis. 2008 Dec;13(12): Mandal C, Dutta A, Mallick A, Chandra S, Misra L,
Sangwan RS, Mandal C. Department of Infectious diseases and Immunology, Indian
Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata 700 032, India.
We demonstrate how Withaferin A exhibits a strong growth-inhibitory effect on several
human leukemic cell lines and on primary cells from patients with lymphoblastic
and myeloid leukemia in a dose-dependent manner, showing no toxicity on normal
human lymphocytes and primitive hematopoietic progenitor cells. Withaferin A
mediated decrease in cell viability was observed through apoptosis. Withaferin A caused increased
levels of Bax in response to MAPK signaling, which resulted in the initiation of
mitochondrial death cascade, and therefore it holds promise as a new,
alternative, inexpensive chemotherapeutic agent for the treatment of patients
with leukemia of both lymphoid and myeloid origin.
Cystic fibrosis
Inhibition of NFkappaB by the natural product Withaferin A in cellular models of
Cystic Fibrosis inflammation.
J Inflamm (Lond). 2009 May. Maitra R, Porter MA, Huang S, Gilmour BP. Center
for Organic and Medicinal Chemistry, The Research Triangle Institute, Research
Triangle Park, NC 27709, USA.
Cystic Fibrosis (CF) is one of the most common autosomal genetic disorders in
humans. This disease is caused by mutations within a single gene, coding for the
cystic fibrosis transmembrane conductance regulator (CFTR) protein. The
phenotypic hallmark of CF is chronic lung infection and associated inflammation
from opportunistic microbes such as Pseudomonas aeruginosa (PA), Haemophilus
influenzae, and Staphylococcus aureus. This eventually leads to deterioration of
lung function and death in most CF patients. Unfortunately, there is no approved
therapy for correcting the genetic defect causal to the disease. Hence,
controlling inflammation and infection in CF patients are critical to disease
management. Accordingly, anti-inflammatory agents and antibiotics are used to
manage chronic inflammation and infection in CF patients. However, most of the
anti-inflammatory agents in CF have severe limitations due to adverse side
effects, and resistance to antibiotics is becoming an even more prominent
problem. Thus, new agents that can be used to control chronic inflammation in CF
are needed in the absence of a cure for the disease. Activation of the
transcription factor NFkappaB through Toll-like receptors (TLR) following
bacterial infection is principally involved in regulating lung inflammation in
CF. NFkappaB regulates the transcription of several genes that are involved in
inflammation, anti-apoptosis and anti-microbial activity, and hyper-activation
of this transcription factor leads to a potent inflammatory response. Thus,
NFkappaB is a potential anti-inflammatory drug target in CF. Screening of
several compounds from natural sources in an in vitro model of CF-related
inflammation wherein NFkappaB is activated by filtrates of a clinically isolated
strain of PA (PAF) led us to Withaferin A, a steroidal lactone from the plant
Withania Somnifera L. Dunal. Our data demonstrate that Withaferin A blocks PAF-induced
activation of NFkappaB as determined using reporter assays, IL-8 measurements
and high-content fluorescent imaging of NFkappaB subunit p65 translocation.
Since the airways of CF patients can be specifically targeted for delivery of
therapeutics, we propose that Withaferin A should be further studied as an
anti-inflammatory agent in models of CF related inflammation mediated by
NFkappaB.
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