Small molecule growth inhibitors from Albatrellus flettii and Sarcodon scabripes native to British Columbia

The first part of this thesis investigated the growth-inhibitory and immunomodulatory potential of six wild Canadian mushrooms. Out of 24 crude extracts, six showed strong growth-inhibitory activity, two exhibited strong immuno-stimulatory activity and nine demonstrated potent anti-inflammatory activity. The second part of this thesis involved purification and characterization of growth-inhibitory compounds from Albatrellus flettii. Liquid-liquid extraction, Sephadex LH-20 and HPLC-Mass Spectrometry (HPLC-MS) were used to purify the three compounds of interest. NMR analyses confirmed their identity as grifolin, neogrifolin and confluentin. Grifolin and neogrifolin inhibited IMP1-KRas RNA interaction as demonstrated using an in-vitro fluorescent polarization assay. The three compounds suppressed KRas expression in SW480 and HT-29 human colon cancer cells. Confluentin, shown for the first time, to induce apoptosis and arrest cell cycle in SW480 cells. The third part of this thesis involved the development of methods to purify growth-inhibitory compounds from Sarcodon scabripes. HPLC-MS detected some potential novel compounds.