Abstract
IntroductionColorectal cancer (CC) is the third most common type of cancer, accounting for 10% of all cancer cases. Adjuvant chemotherapy is recommended in stages II–III CC. Wheatgrass juice (WGJ) from wheat seeds has high nutritional values, may induce synergistic benefits to chemotherapy and may attenuate chemotherapy-related side effects. Extracellular vesicles (EVs) are subcellular membrane blebs. EVs include exosomes (generated in the endosome, in size <150 nm) and microvesicles (shed from the plasma cell membrane) provide information on their parental cells and play a role in intercellular communication. We aimed to elucidate the effects of chemotherapy administration with supportive treatment of WGJ on CC patients’ EVs characteristics.MethodsEVs were isolated from the blood samples of 15 healthy controls (HCs) and 50 CC patients post-surgery, treated by chemotherapy, with or without additional daily WGJ. Blood samples were taken before, during, and at the end of chemotherapy. EVs were characterized by size, concentration, membrane antigens and cytokine content using nanoparticle-tracking analysis, western blot, flow cytometry, and protein array methods.ResultsEVs were found to be similar by size and concentration with reduced levels of exosome markers (CD81) on samples at the end of combined treatment (chemotherapy and WGJ). Higher levels of endothelial EVs, which may indicate impairment of the vascular endothelial cells during treatment, were found in CC patients treated by chemotherapy only compared to those with chemotherapy and daily WGJ. Also, EVs thrombogenicity was lower in patients added WGJ compared to patients who had only chemotherapy (levels of tissue factor p = 0.029 and endothelial protein C receptor p = 0.005). Following treatments, levels of vascular endothelial growth factor receptors (VEGFR-1) and the majority of growth-factors/pro-inflammatory cytokines were higher in EVs of patients treated by chemotherapy only than in EVs obtained from patients with the combined treatment.ConclusionDaily consumption of WGJ during chemotherapy may reduce vascular damage and chemotherapy-related thrombogenicity, growth factors and cytokines, as reflected by the characteristics of patient’s EVs.
Highlights
Colorectal cancer (CC) is the third most common type of cancer, accounting for 10% of all cancer cases
Higher levels of endothelial Extracellular vesicles (EVs), which may indicate impairment of the vascular endothelial cells during treatment, were found in CC patients treated by chemotherapy only compared to those with chemotherapy and daily wheatgrass juice (WGJ)
EVs thrombogenicity was lower in patients added WGJ compared to patients who had only chemotherapy
Summary
Colorectal cancer (CC) is the third most common type of cancer, accounting for 10% of all cancer cases. Wheatgrass juice (WGJ) from wheat seeds has high nutritional values, may induce synergistic benefits to chemotherapy and may attenuate chemotherapyrelated side effects. We aimed to elucidate the effects of chemotherapy administration with supportive treatment of WGJ on CC patients’ EVs characteristics. Six months of adjuvant chemotherapy with fluoropyrimidines, 5-fluorouracil and leucovorin (5-FU/LV) or capecitabine and oxaliplatin is the current worldwide standard of care for patients with stage III colon cancer following curative surgery [1]. For patients with high-risk stage II disease, adjuvant therapy with capecitabine or 5-FU/LV can be considered, as for treatment of stage III disease, according to numerous risk factors [2]. A wide range of health benefits has been attributed to wheatgrass juice (WGJ), the young grass of the common wheat plant Triticum aestivum. In a study of 6-month supplementation of fermented wheat germ extract to anticancer treatments of CC, lower rates of recurrence and longer progression-free and overall survival were reported [5]
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