A promising report was released that describes research into the therapeutic effect of the isothiocyanate sulforaphane, present in cruciferous vegetables, and the polyphenol quercetin on pancreatic cancer cells as well as the ability of pancreatic cancer to build up resistance against them.
Pancreatic ductal adenocarcinoma (PDA) is an aggressive and difficult malignancy to treat. Complete surgical removal of the tumor remains the only chance for cure, however 80-90% of patients have a disease state that is surgically incurable at the time of discovery. Pancreatic adenocarcinoma typically has a very poor prognosis: after diagnosis, 25% of people survive one year and 5% live for five years. Gemcitabine is considered as standard chemotherapy in PDA treatment, despite a low rate of responsiveness due to a marked resistance to chemo and radiotherapy of PDA. The newer combination chemotherapy FOLFIRINOX extends life by 4 months when compared with gemcitabine but has more side effects. Chemoresistance, either acquired or intrinsic, is a major limitation in the successful treatment of pancreatic cancer. The frequent application of chemotherapy to cancer patients happens because it often succeeds in reducing a tumor mass and improves survival. However, the repeated treatment of cancer cells with chemo- or radiotherapy induces therapy resistance.
The researchers in this study wanted to understand whether the same therapy resistance effect occurs upon continuous exposure of cancer cells to diet-derived preventive agents and supplements. They tested this in PDA given its well known resistance toward gemcitabine and other cytotoxic drugs. They choose isothiocyanate sulforaphane, present in cruciferous vegetables, and the polyphenol quercetin, present in many fruits and vegetables for this experiment because several studies exist that suggest sulforaphane and quercetin inhibit proliferation and metastasis, enhances apoptosis and eliminate CSC features in pancreatic cancer.
The researchers used BxPC-3 cells which is a cell line derived from a 61 year old female with a primary adenocarcinoma of the pancreas. The tests showed that isothiocyanate sulforaphane and quercetin did indeed induce apoptosis and reduce viability in BxPC-3 cells but as desired not in non-malignant ductal pancreas cells and mesenchymal stromal cells. The BxPC-3 cells were next treated with increasing concentrations of gemcitabine, sulforaphane or quercetin for more than 1 year (each time the surviving subclones were selected, respectively). The cancer cells largely kept their sensitivity when treated with sulforaphane or quercetin. The gemcitabine treated cells became resistant (interestingly even these resistant cells were still found to be sensitive to sulforaphane and quercetin). The evaluation of the self-renewal-, differentiation- and migration-potential by colony formation, differentiation or migration assays demonstrated that cancer stem cell features were enriched in gemcitabine-resistant cells, but encouragingly decreased in sulforaphane- and quercetin-long time-treated cells. These results were confirmed by xenotransplantation of the cancer cells to mouse pancreas cells where they generated almost undetectable tumors. The gemcitabine-resistant cells however developed large tumors after xenotransplantation. An mRNA expression profiling array and subsequent gene set enrichment analysis also confirmed that tumor progression markers were reduced in sulforaphane- and quercetin-long time-treated cells.
Overall this study demonstrates that the continuous exposure of pancreatic cancer cells to sulforaphane or quercetin does not induce resistance in the surviving cancer cells and importantly reduces tumorigenicity by inhibition of tumor progression markers. These results highlight the potential benefits of plant based supplements as preventive and therapeutic treatment for cancers.
You can find the study here.