November 26 2009 post. You know the bitter taste that you get in your mouth sometimes after biting into a slice of cucumber? Well, years ago my mother showed me how to get rid of that rather bothersome taste, but I won’t be using her method anymore…nope, not after reading what I read earlier today.

The above-mentioned bitterness is caused by a…bitter group of chemicals called cucurbitacins. The more cucurbitacins contained in your cucumber (or any member of the Cucurbitaceae family…melons, pumpkins, squash etc.), the bitterer the taste. The bitterness gives us a sort of warning not to eat the cucumber. But if we are hungry or stubborn enough to ignore the warning, we could develop stomach cramps or worse: back in the 1980s, there were more than 200 cases of zucchini poisoning (!) in Australia, Alabama and California. So: beware of bitter…it could be toxic!

You are probably asking yourselves why I am so interested in this cucurucu-stuff today. Well, it turns out that the cytotoxic properties of all the cucumber family members could be put to good use. This morning a blog reader (thank you!) sent me the link to a study that mentions the fact that cucurbitacins are STAT3 inhibitors, see: http://tinyurl.com/ye3cfmp She also sent me the full study where I found this titbit: Another class of STAT3 inhibitors includes natural products and their derivatives with anti-tumour activities, such as cucurbitacin, resveratrol, galiellalactone, curcumin and indirubin. The molecular mechanisms of action of these natural product inhibitors, which probably inhibit other oncogenic signalling pathways in addition to STAT3, remain to be fully determined.

Since STAT3 is an important signaling pathway in multiple myeloma, I did a quick search of PubMed for studies on cucurbitacins and myeloma. Bingo! I found the abstract of a paper presented at the 2007 ASH annual meeting, see http://tinyurl.com/y9hzgr4 The title says it all: Cucurbitacin I (JSI-124) Has Potent Anti-Myeloma Effects Independent of Its Inhibition of JAK2-Induced STAT3 Activation. I don’t have the full study yet, but there is enough in the abstract to hold our attention: several multiple myeloma cell lines were ultimately trampled to death by JSI-124, or Cucurbitacin I.

This plant extract is identified as a powerful direct inhibitor of myeloma cells blocking constitutive and IL-6/BMSC-dependent STAT3 activation in addition to STAT3 independent signaling pathways. This is clearly excellent news. And there is more: this substance targets both the malignant myeloma cell AND its bone marrow microenvironment, which, as we know by now, is crucial for the cell’s development, growth and survival. A double whammy for our myeloma cells…

Well, this has certainly given me a new appreciation for…cucumbers!