Varsha D. Shiragannavar is a second-year Ph.D. student in the lab of Dr. Prasanna K. Santhekadur at the Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Medical College, JSS AHER, Mysuru. Her doctoral research focuses on understanding the role of RNA-induced silencing complex (RISC) and associated proteins in the development of non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Specifically, she investigates how dietary natural products influence RISC complex genes and proteins.
In this interview, Varsha discusses her first-author publication titled “Withaferin A Acts as a Novel Regulator of Liver X Receptor-α in HCC”, published in Frontiers in Oncology (2021).
Author interview
How would you explain your paper’s key results to the non-scientific community?
Over the last two decades, rapid lifestyle changes globally, including in India, have significantly increased liver-related diseases like NAFLD and HCC. A report by Zydus Cadila indicates that nearly 400 million Indians are affected by fatty liver disease. Despite the large patient population, only a handful of treatment options are currently available, making this area a high-priority focus for pharmaceutical and clinical research.
The famous saying by Hippocrates — “Let food be your medicine and medicine be your food” — is more relevant today than ever. Natural dietary compounds, due to their broad therapeutic effects and minimal side effects, are gaining attention as potential drug candidates.
Ashwagandha (Withania somnifera) is one such ancient medicinal plant, widely used in Ayurvedic medicine for over 3,000 years. Its bioactive compound, Withaferin A, is a steroidal lactone from the withanolide family, found in various parts of the plant (roots, leaves, berries, stems). It has been used for treating stress, inflammation, autoimmune diseases, and even wounds.
In this study, we discovered that Withaferin A significantly inhibits aggressive cancer behaviors in HCC cells. It acts by activating a nuclear receptor, LXR-α, which in turn slows down proliferation, migration, invasion, and cell anchorage-independent growth. It also downregulates NF-κB activation — a major transcription factor associated with cancer progression.
Our work presents a possible novel mechanistic model that Withaferin A may negatively regulate NF-kB transcription factor via activating LXR-α.
What are the possible consequences of these findings for your research area?
Our research shows that Withaferin A activates LXR-α, a nuclear receptor involved in lipid metabolism and immune regulation. This receptor has also been linked with enhancing the effect of sorafenib, a drug used to treat HCC.
While Saroglitazar (an Indian drug) works via PPARα/γ pathways, Withaferin A operates through a different mechanism involving LXR-α. This introduces a new direction for HCC therapy — combining Withaferin A to increase treatment sensitivity and reduce tumor aggressiveness.
Additionally, the study opens up new questions about how Withaferin A interacts with genes and transcription factors, especially in regulating inflammatory signaling and immune responses in liver diseases.
What was the exciting moment (eureka moment) during your research?
My most exciting moments came when we observed that Withaferin A induced expression of LXR-α target genes. Even more exciting was the finding that it inhibited NF-κB target genes through LXR-α activation. These two key observations confirmed our hypothesis and were truly “eureka” moments for me!
What do you hope to do next?
Withaferin A has shown the potential to halt several hallmarks of cancer. Going forward, we aim to:
-
Study the RNA-induced silencing complex in NAFLD and HCC development.
-
Investigate molecular interactions using dietary compounds and their effect on inflammatory pathways, mRNA regulation, protein expression, and post-translational modifications.
-
Conduct in vivo experiments using diet-induced obesity and liver cancer models.
-
Based on promising preclinical data, we plan to move toward Phase I clinical trials in the future.
Where do you seek scientific inspiration?
I have always been curious about how life exists and functions, which is why I chose biology as my core subject. My journey in research began under Dr. Prasanna K. Santhekadur, whose motivational and scientific insights have constantly encouraged me to pursue creative ideas with confidence. His philosophy of “positive imaging in life and science” keeps me grounded and inspired.
We maintain a healthy and supportive lab environment, which motivates me to push boundaries in my doctoral research.
How do you intend to help Indian science improve?
India’s future lies in its young minds. We are planning “Talk to a Scientist” programs for school students to introduce them to the wonders of science in a fun, interactive way.
As a researcher, I hope to contribute by developing novel, affordable drugs for NAFLD and liver cancer, and helping to translate natural compounds into evidence-based therapies.
Reference
Shiragannavar VD, Gowda NGS, Kumar DP, Mirshahi F, Santhekadur PK (2021).
Withaferin A Acts as a Novel Regulator of Liver X Receptor-α in HCC. Front. Oncol. 10:628506.
Edited by: Govinda Raju Yedida (Volunteer, Bio Patrika)
Explore more
🎤 Career – Real career stories and job profiles of life science professionals. Discover current opportunities for students and researchers.
💼 Jobs – The latest job openings and internship alerts across academia and industry.
📢 Advertise with BioPatrika – Reach the Right Audience, Fast!
