Antiproliferative and proapoptotic effect of ascorbyl stearate in human pancreatic cancer cells: association with decreased expression of insulin-like growth factor 1 receptor.
Pancreatic cancer is an aggressive tumor with short median survival and high mortality rate. Alternative therapeutic modalities are currently being evaluated for pancreatic cancer. Here we studied the effects of ascorbyl stearate (Asc-S), a nontoxic, lipophilic derivative of ascorbic acid, on pancreatic cancer. Treatment of human pancreatic carcinoma cells with Asc-S (50-200 microM) resulted in a dose-dependent inhibition of their proliferation. Asc-S slowed down the cell cycle, accumulating, PANC-1 cells in late G2-M phase. Furthermore, Asc-S treatment (150 microM) markedly inhibited growth in soft agar and facilitated apoptosis of PANC-1 cells but not of Capan-2 cells. These effects were accompanied by a significant reduction in insulin-like growth factor 1 receptor (IGF1-R) expression, as compared to untreated controls. Interestingly, Capan-2 cells, the least responsive to Asc-S treatment, did not overexpress the IGF1-R. The results demonstrate the efficacy of Asc-S in inhibing growth of pancreatic cancer cells and warrant additional studies to explore the potential utility of this compound as an alternative and/or adjuvant therapeutic modality for pancreatic cancer.
Naidu
K Akhilender
KA
Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore 570013, India.
Karl
Richard C
RC
Naidu
Kamatham A
KA
Coppola
Domenico
D
D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002214:Capsules; D002453:Cell Cycle / Q000187:drug effects; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017451:Receptors, Somatomedin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D002214:Capsules; D017451:Receptors, Somatomedin; C036225:ascorbyl monostearate; D001205:Ascorbic Acid