Anti-pancreatic Cancer Stem Cell Activity of a Semi-synthetic Andrographolide Derivative

Michelle Dass¹, Dineshwar Sugumaran^2,+, Chee-Woei Lim², Johnson Stanslas^2,*, Audrey Chee-Hui Yong^1,*

Abstract

Introduction: Pancreatic cancer is one of the deadliest cancers, with a high fatality rate approaching 95-100%. The development of pancreatic cancer is strongly affected by cancer stem cells (CSCs), which are a small subset of the cancer population. Current treatment strategies have shown drawbacks in combating pancreatic cancer due to the presence of these cancer stem cells. Moreover, pancreatic cancer cells easily acquire resistance to gemcitabine, standard chemotherapy. Studies have indicated that andrographolide, a naturally occurring agent, exhibits various pharmacological properties, including anti-cancer and anti-inflammatory activities. In this study, the anti-pancreatic cancer stem cell activity of andrographolide and its derivative, Raspholide was evaluated in vitro. Methods: Pancreatic cells Capan-2 were treated with andrographolide, raspholide, as well as dimethylsulfoxide, gemcitabine, sodium chloride, vismodegib (positive control for anti-CSCs), and benzimidazole (anti-Ras agent). The effect of the treatment was assessed via a tumoursphere assay and flow cytometry analysis. Results: It was found that raspholide had a significant effect on the tumorsphere number reduction with a p-value less than 0.05 compared to andrographolide. Raspholide was also able to target the main cancer stem cell markers, CD24+, CD44+, and CD133+ with a value of 4.3%, comparable to vismodegib. Conclusion: Raspholide exhibits anti-cancer activity against pancreatic cancer stem cells.

Keywords: Anti-pancreatic cancer stem cells, Andrographolide, Raspholide, Tumoursphere assay, CD markers

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