Specific 17-Beta-Hydroxywithanolides Sensitize Cancer Cells to Apoptosis in Response to Toll-like Receptor (TLR)

Case ID:

This invention describes the use of withanolide E for cancer treatment through cancer cell apoptosis (cell self-destruction) through extrinsic pathways of “death ligand” proteins. Withanolide E is a natural product in which the 17-beta-hydroxy group and orientation of the molecule chain result in improved apoptosis sensitivity, with demonstrated 4-10x potency. Additionally, these compounds could also sensitize apoptosis in response to synthetic polynucleotides, which are thought to mimic anti-viral responses by activating toll-like receptor signaling.


Traditional treatment for various apoptosis-resistant cancers can be expensive and toxic, causing a range of adverse and difficult side-effects. This has caused a significant demand for new types of cancer treatments that can target resistant cancer cells. Market growth for cancer immunotherapy is strong with rising R&D in a number of advantaged techniques.


Withanolide E has shown promising results over other compounds like withaferin A because the shape of the 17-beta hydroxy group and orientation of the lactone side chain appear crucial for the creation of proteins to selectively kill cancer cells. These compounds also appear to respond to synthetic polynucleotides to mimic anti-viral responses like toll-like receptors that recognize certain damage-associated molecular patterns, and this is of interest to immunologists.


Dr. Gunatilaka co-authored a paper published in 2016 describing cancer cell apoptosis including use of the different compounds. Currently, the inventors hold the only patents specifically describing the use of the withanolide E compound with 17 beta hydroxy group for cancel cell apoptosis: WO/2019/173499 A1 (published 2019-09-12) and US20190046543 A1 (granted 2020-12-01).


  • Treatment of apoptosis-resistant cancers  
  • Treatment of a range of cancers



  • Highly potent at inducing extrinsic apoptosis response
  • Can be used in combination with polynucleotides such as poly IC to stimulate apoptosis

Status: issued U.S. patent #10,849,912

Patent Information:
Contact For More Information:
Tod McCauley
Assistant Director of Licensing, CALS
The University of Arizona
Lead Inventor(s):
Leslie Gunatilaka
Yaming Xu
Kithsiri Wijeratne
Thomas Sayers
Poonam Tewary
Alan Brooks
Curtis Henrich
James McMahon