Antitumoral Drug Potential of Tryptophan-Betaxanthin and Related Plant Betalains in the Caenorhabditis elegans Tumoral Model

Abstract

Betalains are plants pigments identified as potent antioxidant molecules, naturally present in foods like beetroot and prickly pears. Although activities described for betalain-containing formulations include cancer prevention and treatment, the use of extracts instead of purified pigments has avoided the investigation of the real chemopreventive and chemotherapeutic potential of these phytochemicals. Three betalain-rich extracts and six individual pure betalains were used in this work to characterize the activity and to explore possible molecular mechanisms. The animal model Caenorhabditis elegans (tumoral strain JK1466) was used to evaluate the effect of betalains as chemotherapeutics drugs. An objective evaluation method of tumor growth in C. elegans has been developed to assess the possible antitumoral activity of the different treatments. This protocol allowed a fast and reliable screening of possible antitumoral drugs. Among the betalains tested, tryptophan-betaxanthin reduced tumor size by 56.4% and prolonged the animal’s lifespan by 9.3%, indicating high effectiveness and low toxicity. Structure–activity relationships are considered. Assays with mutant strains of C. elegans showed that the mechanism underlying these effects was the modulation of the DAF-16 transcription factor and the insulin signaling pathway. Our results indicate that tryptophan-betaxanthin and related betalains are strong candidates as antitumoral molecules in cancer treatment.

Bougainvillea glabra Choisy bracts extract in free and liposomal forms reduce hyperplasia induced by let‐60gain‐of‐function in Caenorhabditis elegans

“…In C. elegans, betalains reduced tumor growth by modulating DAF-16, extending longevity, and conferring resistance to stress in a gld-1 null mutant model, an orthologous gene model to the human QKI (KH domain with RNA binding capacity). [39] In addition, betaxanthin and betacyanin demonstrated cytotoxic potential in vitro at 0.35 and 0.25 μg/mL, respectively. Nevertheless, only betaxanthin could induce apoptotic signaling, albeit both betalains reduced interleukin-8 (IL-8) production, which is involved in the inflammatory process in some types of cancer, such as colon cancer.…”

“…In C. elegans , betalains reduced tumor growth by modulating DAF‐16, extending longevity, and conferring resistance to stress in a gld‐1 null mutant model, an orthologous gene model to the human QKI (KH domain with RNA binding capacity) [39] . In addition, betaxanthin and betacyanin demonstrated cytotoxic potential in vitro at 0.35 and 0.25 μg/mL, respectively.…”

Betaxanthin Profiling in Relation to the Biological Activities of Red and Yellow Beta vulgaris L. Extracts

“…According to the literature, among the betalains tested, tryptophan-Bx ( 23 ) showed the greatest effect on the size of the tumor by reducing its size by 56.4% in the animal model of Caenorhabditis elegans (cancer strain JK1466) and extended the animal’s lifespan by 9.3%, which indicates high effectiveness and low toxicity [ 63 ]. According to our results, tryptophan-Bx ( 23 ) showed strong activity against HeLa and RKO cell lines, so further in vitro and in vivo studies in this direction on the pure compound are also worth considering.…”

Biological Properties and Applications of Betalains

“…In the interesting tumor model of Caenorhabditis elegans strain JK1466, tumor growth was inhibited by betanin, indicaxanthin, tryptophan-betaxanthin and phenylethylamine-betaxanthin. Interestingly, the sequence of anti-tumor effectiveness of the betalains studied did not correspond to the sequence of their antioxidant effectiveness in vitro and in vivo [ 223 ]. The mechanism of the anticancer action of betalains is still not clear, but it has been demonstrated that betalains affect the expression of some genes related to cell growth and apoptosis [ 216 ].…”