PhD Defense Seminar: Andrew Kunihiro

Bone-Specific Metabolism and Mechanism of Action of Curcuminoids in Blocking Osteolysis in Breast Cancer and Other Resorptive Bone Diseases

Join us for a PhD Defense Seminar!

NSC graduate student Andrew Kunihiro presents "Bone-Specific Metabolism and Mechanism of Action of Curcuminoids in Blocking Osteolysis in Breast Cancer and Other Resorptive Bone Diseases." The turmeric rhizome, which contains a class of dietary polyphenols called curcuminoids, has been used for millennia as a traditional ethnobotanical medicine to treat myriad disorders, including arthritis. Our laboratory has verified the bone protective effects of curcuminoids using pre-clinical models of rheumatoid arthritis and osteoporosis, resorptive disorders where curcuminoids’ protective effects include direct inhibition of bone resorbing osteoclast differentiation. More recently, we have documented the ability of curcuminoids to block the in vivo progression of osteolytic breast cancer bone metastases by inhibiting TGFβ-dependent tumoral secretion of factors driving osteoclastogenesis. However, in all of these resorptive bone diseases it is unclear whether curcumin, the most abundant curcuminoid, or curcuminglucuronide mediates the in vivo protection documented in these studies since curcuminglucuronide is the primary circulating metabolite in rodents and in humans. Because glucuronidation is normally a bio-inactivating process, we hypothesized that curcuminglucuronide could be acting as a pro-drug that is converted to the active aglycone in bone. Thus, studies were undertaken: 1) to determine the effects of glucuronidation and mechanism of action of curcuminoids in blocking TGFβ signaling in breast cancer cells that form TGFβdependent bone metastases in vivo, and 2) to investigate the bone specific metabolism of curcuminoids and other bone protective bone polyphenols that are highly glucuronidated in vivo.