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Open AccessArticle

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

1
Department of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain
2
Department of Biology, Faculty of Sciences, University of Abdelmalek Essaâdi, Tetouan 93000, Morocco
3
Department of Organic Chemistry, Faculty of Marine and Environmental Sciences, University of Cadiz, 11510 Puerto Real (Cádiz), Spain
*
Author to whom correspondence should be addressed.
Foods 2020, 9(3), 300; https://doi.org/10.3390/foods9030300
Received: 30 January 2020 / Revised: 26 February 2020 / Accepted: 3 March 2020 / Published: 6 March 2020
(This article belongs to the Special Issue Bioactive Seaweeds for Food Applications)
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 signal-regulated kinase (ERK) and the AMTs 2, 3, 4, 5, 7, and 8 decreased phosphorylation of c-JUN N-terminal 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. View Full-Text
Keywords: meroterpenoids; Cystoseira usneoides; colon cancer; HT-29; cell cycle; apoptosis; metastasis meroterpenoids; Cystoseira usneoides; colon cancer; HT-29; cell cycle; apoptosis; metastasis
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Zbakh, H.; Zubía, E.; De Los Reyes, C.; Calderón-Montaño, J.M.; Motilva, V. Anticancer Activities of Meroterpenoids Isolated from the Brown Alga Cystoseira usneoides against the Human Colon Cancer Cells HT-29. Foods 2020, 9, 300.

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