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Obesity-associated Leptin Concentrations Inhibit Chemotherapeutic Drug, Panobinostat, and Induced Death in Myeloma Cell Lines

Renshal Joaquin and Jeffrey Handy, Ph.D., Department of Biology, Morehouse College. 830 Westview Drive. Atlanta, Georgia 30314

According to the WHO, over 650 million adults worldwide are obese.  Obesity is the excessive accumulation of fat that may impair health. An obese individual has a BMI of 30 or higher. The excess accumulation of body fat increases the risk of developing several cancers while also worsening a patient’s prognosis after diagnosis with particular cancers, such as multiple myeloma. According to the NIH, obese individuals have a 10% to 20% increase in the risk of developing multiple myeloma. Long-term obesity is frequently associated with abnormal circulating levels of adipokines, bioactive molecules that promote metabolism, inflammation, and cell proliferation.  Leptin, an adipokine that suppresses appetite and food intake, regulates body weight and may promote multiple myeloma by reducing the likelihood of apoptosis in cancerous cells. This study was conducted to determine if obesity-associated concentrations of leptin affects KMS11, a human myeloma cell line, cell sensitivity to the chemotherapeutic agent Panobinostat . Panobinostat is an anti-cancer drug commonly classified as a “Histone Deacetylase Inhibitor”. Our working hypothesis was that obesity-associated concentrations of leptin desensitize cancer cells to conventional anti-cancer chemotherapeutics. To test this hypothesis,we exposed cultures of KMS11 cells to an effective dose of PBST (52 nM) in the absence and presence of increasing concentrations of leptin (6, 45, 50, 60ng/ml) for 24 hours, then measured cellular viability. At 52nM PBST, the relative fraction of living KMS11 cells was 57% of what was measured in the untreated sample. In the presence of PBST and leptin, however, the relative fraction of living cells increased from 65% of the untreated to 100% of the untreated as the concentration of leptin increased. These in vitro findings suggest that obesity-associated concentrations of leptin desensitize KMS11 cells to panobinostat, and also suggest that similar experiments should be conducted with other myeloma cell lines and drugs. 




Additional Abstract Information

Presenter: Renshal Joaquin

Institution: Morehouse College

Type: Poster

Subject: Biology

Status: Approved


Time and Location

Session: Poster 2
Date/Time: Mon 3:00pm-4:00pm
Session Number: 2674