An Original 3D Culture Model: Human Pancreatic Cancerous Organoids Generated in Liquid Pearls

Christian D. Muller
Dr. ès Sciences, Ph.D.
CSO & Founder, PearlBioSystem 

In recent years, interest in medicinal Cannabis sativa L. has been rising, as legislation is moving in the right direction. In our laboratory we compared different cannabinoid extraction methods to identify and quantify the compounds exhibiting anti-cancer activity on human pancreatic cells. To compare and study the mechanism of action of such natural plant extracts we wanted to be as close as possible to the situation in the patient by using an original 3D culture model i.e., liquid pearls which is a crucial first step in this study. It helped to validate the efficacy of the extracts in a test as close as possible to the in vivo situation. Such a testing had to be performed, prior to any other experiment, to avoid any false positive responses often obtained in 2D biology, as such a flat culture method is a long way from the physiology of a human organism.

Apoptosis is defined by a set of physical features that are associated with the demise of an individual cell. It’s probably one of the most common forms of cell death during the development of an organism. It also plays an important role in cancer. One way to cure cancer is to induce apoptosis so to eliminate cells that contain potentially dangerous mutations. If a cell’s apoptosis function is not working properly, the cell can grow and divide uncontrollably and ultimately create a tumour.

As we found apoptosis induction by Cannabis sativa L. extracts in a pancreatic cancer line widely described for his high drug resistance, such a mechanistic study was never performed with human pancreatic organoids generated in Liquid Pearls. While gemcitabine, a gold standard drug in the treatment of pancreatic cancer, only triggers cell cycle arrest, the cannabinoid extracts activate the cell signalling cascade leading to apoptotic programmed cell death. The results reported in our paper emphasise the potential of natural products issued from medicinal hemp for pancreatic cancer therapy, as they lead to an accumulation of intracellular superoxide ions, affect the mitochondrial membrane potential, induce cell cycle arrest, and ultimately drive the pancreatic cancer cell to lethal apoptosis.