Adipocytes absorb and metabolize the chemotherapeutic agent daunorubicin, reducing the effectiveness of the drug, according to new research conducted by UCLA researchers and published today in Molecular Cancer Research.
"Anthracyclines such as daunorubicin are important chemotherapy agents used in a variety of cancers in children and adults, including leukemia," Steven Mittelman, M.D., Ph.D., associate professor of pediatrics and the division chief of pediatric endocrinology at UCLA Mattel Children's Hospital, explained. "We need to better understand how some leukemia cells are able to avoid and resist this and other chemotherapies, so we can develop better strategies to improve our treatment outcomes."
In order to determine how obesity might impact the effectiveness of daunorubicin, Mittelman and colleagues co-cultured human acute lymphoblastic leukemia (ALL) cell lines with adipocytes and treated them with daunorubicin. They also studied whether human adipose tissue from cancer patients could metabolize daunorubicin. They measured the presence of daunorubicin through flow cytometry and liquid chromatography/mass spectrometry, and examined fat cells in bone marrow from children with leukemia.
They found that the presence of adipocytes significantly reduced the accumulation of daunorubicin in the ALL cells; the adipocytes absorbed the chemotherapeutic agent, removing it from the leukemia microenvironment; and the adipocytes metabolized daunorubicin.
"The finding that human fat cells can metabolize and inactivate a chemotherapy is novel and surprising," Mittelman said. "This is important for leukemia and a lot of other cancers that grow in the bone marrow or around fat cells, since that means that fat cells might remove chemotherapy from the environment and allow the cancer cells to survive."