Antitumor Effect of the Ethanolic Extract from Seeds of Euphorbia lathyris in Colorectal Cancer

Cristina Mesas,Rosario Martínez,Raúl Ortíz,María López-Jurado,Milagros Galisteo,Laura Cabeza,Jose Prados,Consolación Melguizo,Jesús M Porres,Gloria Perazzoli

doi:10.3390/nu13020566

Abstract

The seeds of Euphorbia lathyris have been used in traditional medicine to treat various medical conditions. However, neither all of their active biocompounds nor the molecular mechanisms underlying their therapeutic effects have been described. A new ethanolic extract of defatted flour from mature seeds of Euphorbia lathyris showed a high total polyphenol content and significant antioxidant activity. Chromatographic analysis showed that esculetin, euphorbetin, gaultherin, and kaempferol-3-rutinoside were the most abundant polyphenolic bioactive compounds. Antiproliferative assays showed a high and selective antitumor activity against colon cancer cell lines (T84 and HCT-15). In addition, a significant antiproliferative activity against glioblastoma multiforme cells was also demonstrated. Its mechanism of action to induce cell death was mediated by the overexpression of caspases 9, 3, and 8, and by activation of autophagy. Interestingly, a reduction in the migration capacity of colon cancer cells and a significant antiangiogenic effect on human umbilical vein endothelial cells were also demonstrated. Finally, the extract significantly reduced the subpopulations of cancer stem cells. This extract could be the basis to develop new therapeutic strategies for the treatment of colon cancer, although further experiments will be necessary to determine its in vivo effects.

Highlights

Population aging, nutrition, and sedentary lifestyle are related to the severe increase in the prevalence of colorectal cancer (CRC), which currently represents the third most common cancer worldwide [1,2]
In order to determine the molecular mechanism of cell death induced by the ethanolic extracts from the defatted flour of seeds of Euphorbia lathyris, caspase expression, cell microtubules polymerization/depolymerization, and autophagy were analyzed
The significant formation of autophagy vesicles around the cell nucleus was detected in cell lines exposed to the extract (Figure 6C)

Summary

Introduction

Population aging, nutrition, and sedentary lifestyle are related to the severe increase in the prevalence of colorectal cancer (CRC), which currently represents the third most common cancer worldwide [1,2]. CRC [3], but chemotherapy is still required in advanced (metastatic) cancer. Monoclonal antibodies and multiple kinase inhibitors have enhanced its prognosis [4], the success of chemotherapy against this tumor is yet subject to the discovery of new anticancer agents. In this context, the activity of plant extracts or derivatives on the viability and survival of tumor cells has gained increasing interest [5]. Euphorbia comprises a great diversity of plants from the spurge family (Euphorbiaceae), containing more than 2000 species [6].

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