When cells are subject certain types of mild stress, it activates a protein called NF-κB and downstream pathways that can lead to future stress resistance in a process called pre-conditioning. This is useful for preparing cells for transplant into harsh environments. But there are other situations where you don’t want these same survival proteins active and keeping cells alive.
One such instance is when targetting cells with chemotherapy. Cells that survive treatment can regrow into tumours that can be resistant to further treatment. Sorafenib is a drug that inhibits pathways involved in tumour blood-vessel growth, and tumour progression in general, and has been implicated in targeting cancer stem cells. It has been used to treat kidney and liver cancers, and more recently tested for use with pancreatic cancer.
Pancreatic cancer is increasingly thought to be driven by cancer stem cells. Sorafenib has shown anti-tumour activity in pancreatic cancer, but its effectiveness is limited: after an initial responsive period, the cells bounce back with enhanced tumour progression and increased metastasis. This is possibly due to a cancer stem cell population that survives treatment, leading to this renewed growth. One reason these cells survive is that sorafenib activates NF-κB survival pathways.
Recent research published in Cancer Research attempts to enhance the effectiveness of sorafenib by interfering with NF-κB. In this paper, the authors show that sorafenib reduces — but doesn’t completely eliminate — the stem cell properties of pancreatic cancer cell lines. Some cells survive, and with time regrow. The same was shown in vivo when cancer stem cell rich pancreatic cells were transplanted into mice. However, when the cells were pre-treated with a different chemical, sulforaphane, before applying the drug, there was enhanced cell death and increased inhibition of stem cell characteristics such as morphology and colony and spheroid formation compared to either compound on its own. Furthermore, addition of sulforaphane interfered with cell survival pathways, completely abolishing sorafenib-dependent NF-κB activation. This enhancement of sorafenib activity was seen both in vitro and in mouse models for pancreatic cancer. This suggests that combination with an NF-κB inhibitor such as sulforaphane could be a therapeutic option for improving certain cancer therapies that target cancer stem cells.
So where does sulforaphane come from? You can get it from your diet. Foods like broccoli and cauliflower are rich in the anti-cancer compound, hinting at nutritional ways to break cancer stem cell resistance to therapy.
All the more reason to eat your veggies.