The inhibitory effects of dietary agents, benzyl isothiocyanate and sulforaphane in pancreatic cancer cells

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Pancreatic cancer is one of the most serious cancers. Each year about 32,000 individuals in the United States are diagnosed with pancreatic cancer. According to the American Cancer Society, there are estimated 37,170 new cases and 33,370 deaths from pancreatic cancer in the United States in 2007. Cancer of the exocrine pancreas is rarely curable and has an overall survival rate of less than 4%. The highest cure rate occurs if the tumor is truly localized to the pancreas; however, this stage of the disease accounts for fewer than 20% of cases. For those patients with localized disease and small cancers (<2 cm) with no lymph node metastases and no extension beyond the capsule of the pancreas, complete surgical resection can yield actuarial 5-year survival rates of 18% to 24%. For patients with advanced cancers, the overall survival rate of all stages is less than 1% at 5 years with most patients dying within 1 year. Hence, there is an urgent need to develop more effective preventive and therapeutic approaches for pancreatic cancer. Patients with any stage of pancreatic cancer can appropriately be considered candidates for clinical trials using new preventive and therapeutic approaches because of the poor response to chemotherapy and radiation therapy as conventionally used. The etiology of pancreatic cancer is still not well understood but involves a multi-step process of signaling protein dysregulation.
 >We examined the inhibitory activity of bioactive compounds from Cruciferous vegetables, Benzyl isothiocyanate (BITC) and sulforaphane, 3,3'-diindolylmethane (DIM) in human pancreatic cancer cell lines, PANC-1 and HPAC. BITC and sulforaphane inhibited cell viability and induced apoptosis of PANC-1 and HPAC human pancreatic cancer cell lines, while DIM had much less inhibitory effects in both pancreatic cancer cell lines. Because the constitutive activation of Signal Transducer and Activator of Transcription 3 (Stat3) is frequently detected in pancreatic cancer and contributes to angiogenesis, survival, and growth of pancreatic cancer cells, we examined whether BITC might inhibit Stat3 pathway. Interestingly, BITC inhibited the tyrosine phosphorylation of Stat3 but did not inhibit the phosphorylation of ERK1/2 MAPK and p70S6 kinase suggesting that Stat3 is one of the targets of BITC-mediated inhibition in these cancer cells. Combinations of lower doses of BITC and sulforaphane inhibited cell viability and induced apoptosis more dramatically than single agent alone in PANC-1 and HPAC pancreatic cancer cell lines. These results suggest that dietary agents, BITC and sulforaphane have potent inhibitory activity in human PANC-1 and HPAC pancreatic cancer cells and may have translational potential for chemoprevention or therapeutic agents for pancreatic cancer.