New withanolides with TRAIL-sensitizing effect from Physalis pubescens L

Area of Science:

• Natural Product Chemistry
• Pharmacology
• Cancer Biology

Background:

• Physalis pubescens L. (husk tomato) is known for nutritious fruits, but its bioactive compounds remain largely uncharacterized.
• Withanolides, a class of steroidal lactones, are known for diverse biological activities.

Purpose of the Study:

• To isolate and characterize novel bioactive compounds from Physalis pubescens L.
• To evaluate the anti-cancer potential of isolated compounds against human renal cell carcinoma (RCC).

Main Methods:

• Isolation and structural elucidation of withanolides using extensive spectroscopic analyses.
• In vitro anti-proliferative assays against four human RCC cell lines.
• Apoptosis induction studies, including Western blotting and molecular docking.

Main Results:

• Four new withanolides (1-4) and one known withanolide (5) were identified.
• Compounds 1, 3, and 5 exhibited significant growth inhibitory effects on RCC cell lines, with compound 1 being the most potent (IC50s 0.30–0.77 μM).
• Compound 1 enhanced TRAIL-induced apoptosis in 786-O RCC cells by upregulating CHOP and DR5, activating the DR5/caspase-8/3 pathway.

Conclusions:

• A novel withanolide (1) from Physalis pubescens L. demonstrates potent anti-cancer activity against renal cell carcinoma.
• Compound 1 acts as a lead compound for potential RCC therapeutics by inducing apoptosis through the TRAIL/DR5 pathway.
• Further investigation of this withanolide is warranted for RCC prevention and treatment strategies.