Anticancer Activities of Meroterpenoids Isolated from the Brown Alga Cystoseira usneoides against the Human Colon Cancer Cells HT-29.

Colorectal cancer (CRC) is one of the most common types of cancers and a leading cause of cancer death worldwide. The current treatment for CRC mainly involves surgery, radiotherapy, and chemotherapy. However, due to the side effects and the emergence of drug resistance, the search for new anticancer agents, pharmacologically safe and effective, is needed. In the present study, we have investigated the anticancer effects of eight algal meroterpenoids (AMTs, 1-8) isolated from the brown seaweed Cystoseira usneoides and their underlying mechanisms of action using HT-29, a highly metastatic human colon cancer cell line. All the tested meroterpenoids inhibited the growth of HT-29 malignant cells and were less toxic towards non-cancer colon cells, with the AMTs 1 and 5 exhibiting selectivity indexes of 5.26 and 5.23, respectively. Treatment of HT-29 cells with the AMTs 1, 2, 3, 4, 5, and 7 induced cell cycle arrest in G2/M phase and, in some instances, apoptosis (compounds 2, 3, and 5). Compounds 1-8 also exhibited significant inhibitory effects on the migration and/or invasion of colon cancer cells. Mechanistic analysis demonstrated that the AMTs 1, 2, 5, 6, 7, and 8 reduced phosphorylation levels of extracellular signal­regulated kinase (ERK) and the AMTs 2, 3, 4, 5, 7, and 8 decreased phosphorylation of c­JUN N­terminal kinase (JNK). Moreover, the AMTs 1, 2, 3, 4, 7, and 8 inhibited phosphorylation levels of protein kinase B (AKT) in colon carcinoma cells. These results provide new insights into the mechanisms and functions of the meroterpenoids of C. usneoides, which exhibit an anticancer effect on HT-29 colon cancer cells by inducing cell cycle arrest and apoptosis via the downregulation of ERK/JNK/AKT signaling pathways.

Preventive effect of the microalga Chlamydomonas debaryana on the acute phase of experimental colitis in rats.

Inflammatory bowel diseases (IBD) are characterised by chronic uncontrolled inflammation of intestinal mucosa. Diet and nutritional factors have emerged as possible interventions for IBD. Microalgae are rich sources of n-3 PUFA and derived oxylipins. Oxylipins are lipid mediators involved in the resolution of many inflammatory disorders. The aim of the present study was to investigate the effects of the oxylipin-containing biomass of the microalga Chlamydomonas debaryana and its major oxylipin constituent, (9Z,11E,13S,15Z)-13-hydroxyoctadeca-9,11,15-trienoic acid ((13S)-HOTE), on acute 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. Lyophilised microalgal biomass and (13S)-HOTE were administered by oral route 48, 24 and 1 h before the induction of colitis and 24 h later, and the rats were killed after 48 h. The treatment with the lyophilised microalga and (13S)-HOTE improved body-weight loss and colon shortening, as well as attenuated the extent of colonic damage and increased mucus production. Cellular neutrophil infiltration, with the subsequent increase in myeloperoxidase levels induced by TNBS, were also reduced after the administration of the lyophilised microalga or (13S)-HOTE. The anti-inflammatory effects of these treatments were confirmed by the inhibition of colonic TNF-α production. Moreover, lyophilised microalga or (13S)-HOTE down-regulated cyclo-oxygenase-2 and inducible nitric oxide synthase expression. The present study was the first to show the prophylactic effects of a lyophilised biomass sample of the microalga C. debaryana and the oxylipin (13S)-HOTE on TNBS-induced acute colitis in rats. Our findings suggest that the microalga C. debaryana or derived oxylipins could be used as nutraceuticals in the treatment of the active phase of IBD.