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