Cucurbitacins may be a taste deterrent in plants foraged by some animals and in some edible plants preferred by humans, like cucumbers. In laboratory research, cucurbitacins have cytotoxic properties and are under study for their potential biological activities.
The biosynthesis of cucurbitacin C has been described. Zhang et al. (2014) identified nine cucumber genes in the pathway for biosynthesis of cucurbitacin C and elucidated four catalytic steps. These authors also discovered the transcription factorsBl (Bitter leaf) and Bt (Bitter fruit) that regulate this pathway in leaves and fruits, respectively. The Bi gene confers bitterness to the entire plant and is genetically associated with an operon-like gene cluster, similar to the gene cluster involved in thalianol biosynthesis in Arabidopsis. Fruit bitterness requires both Bi and the dominant Bt (Bitter fruit) gene. Nonbitterness of cultivated cucumber fruit is conferred by bt, an allele selected during domestication. Bi is a member of the oxidosqualene cyclase (OSC) gene family. Phylogenetic analysis showed that Bi is the ortholog of cucurbitadienol synthase gene CPQ in squash (Cucurbita pepo) 
There are several substances that can be seen as derving from cucurbita-5-ene skeleton by loss of one of the methyl groups (28 or 29) attached to carbon 4; often with the adjacent ring (ring A) becoming aromatic.:87-130
Several other cucurbitacins have been found in plants.:152-156,164-165
The toxicity associated with consumption of foods high in cucurbatincs is sometimes referred to as "toxic squash syndrome". In France in 2018, two women who ate soup made from bitter pumpkins became sick, involving nausea, vomiting, and diarrhea, and had hair loss weeks later. Another French study of poisoning from bitter squash consumption found similar acute illnesses and no deaths. The high concentration of toxin in the plants could result from cross-pollination with wild cucurbitaceae species, or from plant growth stress due to high temperature and drought.
Research on antitumor activity of cucurbitacin focuses on four main variants of this molecule. Cucurbitacins with the most prominent antitumor activity are B, D, E and I. Of these, cucurbitacin B and D are the most common in plants. The mechanisms by which it affects cancer cells are mainly inhibition of STAT3 signaling pathway, induction of apoptosis and cell cycle arrest. It also affects function of proteasome and inflammasome.
Pathologists found cucurbitacin in the stomach of a 79-year-old man who died in Baden-Württemberg, Germany, shortly after eating a casserole containing zucchini he had received from a neighbor.
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