Combination of Anti-Diabetic Drug Metformin and Boswellic Acid Nanoparticles: A Novel Strategy for Pancreatic Cancer Therapy

Pancreatic cancer has an infaust prognosis and is the fourth common cause of cancer related death in India. It is highly resistant to conventional treatment modalities such as chemotherapy, radiation therapy and surgery. The association of pancreatic cancer and diabetes mellitus is explored in our study. Pancreatic cancer is more likely to occur in people who have diabetes than people devoid of it, which is supported by the observation that hyperglycaemia occurs at an early stage of pancreatic cancer and is indeed a risk factor. In the present study, we have demonstrated a synergistic relationship between metformin and boswellic acid nanoparticles with varying doses of boswellic acid nanoparticles and constant metformin (20 mM). The effect revealed increased synergism between metformin and boswellic acid nanoparticles through the inhibition of cell proliferation with an effect of 80% for the combination with 0.3 mg/mL and 0.4 mg/mL and a constant concentration of metformin. We examined the effect of combination on cell migration which revealed time dependent inhibitory effect on pancreatic cell line (MiaPaCa-2). Also, we found that the combinatorial approach significantly decreased colony formation and exhibited high rate of induction of apoptosis through DNA fragmentation in pancreatic cancer cells. In-vitro hemolysis confirmed the hemocompatibility of the combination therapy with metformin and boswellic acid nanoparticles. Flow cytometry based apoptosis assay and Caspase mediated apoptosis proved apoptosis mediated cell death. Further, the cells were analysed with mitochondrial membrane potential kit which revealed depolarization of mitochondrial membrane potential due to apoptosis after treatment with drug combination. Hence, the combination approach proved to be a promising therapy towards pancreatic cancer.