Anti-Cancer Effect of Sulforaphane in Human Pancreatic Cancer Cells Mia PaCa-2.

[BACKGROUND] Pancreatic cancer is difficult to treat early as it has no early symptoms. The presence of sulforaphane (SFN) in cruciferous vegetables has been found to possess anti-cancer effects in gastric and colon cancers. Glycogen synthase kinase-3 beta (GSK-3β), a serine/threonine kinase, plays a significant role in pancreatic cancer progression, influencing tumor growth, metastasis, and treatment resistance. Targeting GSK-3β has shown potential to enhance the efficacy of chemotherapy. However, the mechanism underlying the anticancer effects of SFN on pancreatic cancer through GSK-3β is unclear.

[AIMS] In this study, we examined the anticancer effects of SFN in human pancreatic cancer cell line Mia PaCa-2 and evaluated its molecular mechanisms with respect to the GSK-3β-related pathway.

[METHODS AND RESULTS] SFN increased the protein expression of the phosphorylated form of GSK3β (Ser9). In the Wingless Int-1 homolog/β-catenin pathway, GSK3β induced apoptosis by phosphorylating β-catenin. However, in mutant Kirsten rat sarcoma viral oncogene homolog-like-dependent cells such as Mia PaCa-2, GSK3β was suppressed and the β-catenin level was increased, thus inducing apoptosis. Indeed, SFN increased the protein expression of β-catenin in the cytoplasm and nucleus. Subsequently, we measured the level of cMyc, the target gene of β-catenin. SFN decreased cMyc expression despite an increase in the β-catenin. We measured the expression of nuclear factor (NF)-κB, a downstream factor of GSK3β and an upstream factor of cMyc. SFN decreased the expression of NF-κB and cMyc, indicating that SFN inhibits cell proliferation by suppressing the GSK3β/NF-κB/cMyc pathway. As the suppression of NF-κB results in a decrease in B-cell lymphoma 2 (BCL-2) which is the anti-apoptotic gene, we tested the effect of SFN in the expression of BCL-2. SFN inhibited the expression of BCL-2 and increased the ratio of the apoptotic regulator gene BCL-2 associated X (BAX), where SFN induced the cleaved cysteine aspartase-3 and poly-adenosine diphosphate ribose polymerase.

[CONCLUSION] These results indicate that SFN may have therapeutic potential in the inhibition of pancreatic cancer.