ABSTRACT:
Human embryonic stem cells (HESCS) are a unique cell type isolated from the inner cell mass of pre-implantation blastocysts'. Theoretically, HESCS are capable of unlimited self-renewal and can differentiate to every somatic cell type in the body. In addition to that they may provide a system to study early human development in vitro, and in the future, differentiated populations can be used for cell replacement therapies. The advent of defined media and controlled differentiation has enabled screening of hESCs to discover molecules that impact growth, differentiation or apoptosis in undifferentiated and differentiating populations. Small molecules such as natural products could be highly valuable in the progression of cell therapy technologies, or could be novel therapeutics in their own right, providing tools for embryonic cell populations that cannot be targeted with other approaches. In our ongoing research program of screening pre-fractionated and. semi-purified extracts of plants in an effort to discover compounds that impact hESCs growth using a 96-well plate real-time cell electronic sensing (RT-CES) system, activity was discovered for the extract of the Magnolia grandiflora. A large-scale extraction and purification yielded two new diterpenoids (1-2), along with known compounds (3-6). The cell growth inhibitory activities of compounds 1-6 were evaluated against HESCS (BG02) and a pancreatic cell line (BXPC-3) using an RT-CES system. Compounds (1) showed the greatest growth inhibition against both the BG02 and BXPC-3 cells with ECS0 values of 2.4 and 9.3 pM, respectively.