Capsaicin cancer of the prostate

Another use for capsaicin, cancer cure?

In an experiment with mice, Mori et al. (2006) reported in Cancer Research that 5mg/kg/d of orally administered capsaicin decreased the size of prostate cancer tumors by 78%. This is pretty exciting. It’s the equivalent of about one habanero pepper per day in humans.

It is known that these cells express the “capsaicin receptor” Transient Receptor Potential Vanilloid-like 1 (TRPV1 aka. VR1) (Sanchez et al. 2005). Using in vitro techniques, they also reported that this effect was not due to capsaicin’s interaction with TRPV1. Cultured prostate cancer cells grown with the TRPV1 specific antagonist capsazepine, still were killed by treatment with capsaicin.

It gets pretty sciencey from here, so for those of you who don’t care or don’t like biochemistry, I will summarize what is below in layman’s terms, in a single paragraph (if you want to know the biochemistry just skip this paragraph). It doesn’t kill them through its receptor. It does affect a protein (NFkB) which changes the expression of other genes in the cell, and NFkB is known to be necessary for most prostate cancers to survive – although it is not known how or why it affects NFkB. It also affects the expression of a bunch of well studied signaling pathways, not surprising because everything affects these major pathways (that’s why they’re considered “major”). It probably has its main action through a different, unknown protein, since another compound, capsazepine, which has a similar structure to capsaicin also kills prostate cancer cells.

So, more specifically, how does capsaicin kill prostate cancer cells? The specific mechanism is not yet known, however TRPV1 is not the only protein that capsaicin is known to interact with. The authors of the aforementioned study found that capsaicin inhibits nuclear translocation of the transcription factor Nuclear Factor kappa B (NFkB). Constitutive NFkB activity in prostate cancer is high. The authors found that capsaicin inhibits the degradation of IkBa, which is a subunit of NFkB which inhibits the activity of it by inhibiting its translocation to the nucleus. Proteasomes are what degrade IkBa, and capsaicin inhibited protease activity (which is normally high in these cancer cells).

A separate study (Sanchez et al. 2007) concluded that capsaicin is a generator of reactive oxygen species (ROS), it activates c-jun N-terminal kinase (JNK), leads to ceramide accumulation, and activates MAPKK but not MAPK (ERK), and proposed that it is through these mechanisms that capsaicin induces apoptosis (death) in prostate cancer. These pathways are some of the most well studied, and major, signaling pathways and are active in almost all cell types. It is not surprising that a foreign molecule could activate these pathways. If you look at some cells types wrong these pathways will become active, so this study isn’t really telling us much, but I thought I would include their conclusions here as someone else may interpret them differently.

Interestingly, there is a study reporting that capsazepine kills 37% of prostate cancer cells in vitro. To me, this further confirms that this effect is not due to capsaicin’s interaction with TRPV1. However, given the structural homology between capsaicin and capsazepine, and they both kill cancer cells, there is probably another unknown protein interaction for which both capsaicin and capsazepine act as either agonists or antagonists.

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