Integrative Biology

Therapy of breast cancer metastasis with UBS109:An estimated 30% of women diagnosed with invasive breast cancer will have a recurrence and may eventually die of their disease. An estimated 90% of deaths due to breast cancer area consequence of metastatic disease. Bone is one of the most common sites (70%) of metastasis.Monocarbonyl analogs of curcumin (MACs) include UBS109, EF31 and EF24. UBS109 inhibited bone destruction induced by triple-negative breast cancer (TNBC) MDA-MB-231 cells. UBS109 directly stimulates osteoblastogenesis and mineralization in bone marrow cells from normal nude mice in vitro and stimulates osteoblast activation in preosteoblastic cells. Furthermore,UBS109 suppresses the diff erentiation of osteoclast precursors into mature osteoclasts. UBS109 inhibited breast cancer in the bone, osteolysis by inhibiting osteoclast precursors and osteoclasts, but promotes new bone formation by stimulating osteoblast activation. Recently, we have demonstrated that UBS109 inhibited lung metastasis of the TNBC. Novel therapy for pancreaticand colon cancer using UBS109: Pancreatic ductal adenocarcinoma (PDA) is the fourth most common cause of cancer death, the

overall 5-year survival for PDA is less than 5%, a median survival of 4–6 months. Pancreatic cancer (PC) has a high incidence of clotting complications. We tested the cytotoxic activity of UBS109, EF31, EF24, HSP90 inhibitor, gemcitabine (current treatment), Akt inhibitor and p38 MAPK inhibitor against four diff erent PC cells.UBS109 and EF24 inhibited 100% at less than 1.25 μM, but others did not inhibit 100% at concentrations up to 20 μM. UBS109 and EF31(25 mg/kg, I.V.)/week for 3 weeks signifi cantly inhibited MiaPaCa-2 xenograft s in mice.UBS109 (25 mg/kg, I.V.)/week inhibited colon cancer (HT-29 and HCT- 116) xenograft s better than a combination of oxaliplatin (5 mg/kg) and 5FU (30 mg/kg) I.V.