INDOLE-3-CARBINOL (I3C) ENHANCES CHEMO-SENSISTIVITY OF GEMCITABINE IN LEIOMYOSARCOMA

Introduction: Adjuvant Gemcitabine has shown improvement of progression free survival in a few leiomyosarcoma cases, yet the biochemical reason is unknown. We hypothesized that chemo-responsiveness of gemcitabine can be... [ view full abstract ]

Introduction: Adjuvant Gemcitabine has shown improvement of progression free survival in a few leiomyosarcoma cases, yet the biochemical reason is unknown. We hypothesized that chemo-responsiveness of gemcitabine can be enhanced by inducing human nucleotide transporter (hENT1) expression, boosting cellular uptake. Indole-3-carbinol (I3C) has been known to enhance the hENT1 expression. Therefore, we studied the role of I3C towards enhancing the chemoresponsiveness of gemcitabine in leimyosarcoma treatment. Methods: Leiomyosarcoma cells (SKLMS) were incubated, plated and allowed to adhere. Then, treated with gemcitabine in the presence or absence of I3C and compared with controls. MTS cell viability assays were done and absorbance was monitored in a micro-plate reader. Flow cytometry was performed with Propidium Iodide (PI) staining. Scratch assays were done to assess cell migration. Results: Viability assay showed an increase in the cytotoxicity of gemcitabine in presence of I3C compared to controls. Flow cytometry data showed gemcitabine alone arrested the cell cycle at G0/G1 phase without increase of cell death.  Gemcitabine in combination with I3C increased cell death by at least three folds compared to control as well as the gemcitabine alone treated cell population. Scratch assay showed that the rate of cellular migration dropped by 1.5 folds with gemcitabine combined with I3C compared to gemcitabine alone.Conclusion: The use of I3C enhanced cellular uptake and cytotoxicity of gemcitabine in SKLMS cells. Further studies are warranted and underway to elaborate on intracellular mechanisms of action to optimize the use of I3C as a potential adjunct in preclinical and clinical leiomyosarcoma treatment.