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

Abstract

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.

Structure Elucidation and Anti-Tumor Activities of Trichothecenes from Endophytic Fungus Fusariumsporotrichioides

“…In this case, it is necessary to inhibit cell progress before mitotic entry [ 23 ]. Due to DNA damage, the cells activate an apoptotic program and halt mitotic during the metaphase [ 24 ]. In this study, our result demonstrated that the growth inhibitory effect of the 3 on Huh-7 cells was associated with a G2/M arrest and cell cycle progression.…”

Algal Terpenoids: A Potential Source of Antioxidants for Cancer Therapy

“…Eight meroterpenoids have been isolated from this seaweed which have anti-colon and anti-lung cancer activity. These meroterpenoids can hinder growth and migration of colon cancer cells by suppressing ERK/JNK/AKT pathways, as well as can arrest cells at G2/M phase [60]. Similarly, these meroterpenoids displayed anticancer effect against lung carcinoma, while blocks lung cancer cells at G2/M and S phases [61].…”

Anti-Inflammatory and Anticancer Effects of Microalgal Carotenoids

“…From a molecular and intracellular point of view, during the inflammatory process, a coordinated activation of several signaling pathways is triggered, including phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), mitogen-activated protein kinase (MAPK), Janus kinase/signal transduction and activator of transcription (JAK/STAT), or the key transcriptional element nuclear factor-kappa B (NF-κB) that interacts with different nuclear or cytoplasmic elements, including PPAR-γ, which is capable of inhibiting NF-κB activation and the consequent production of numerous cytokines [104][105][106]. The activation through the innate immune system occurs by pattern recognition receptors (PRRs) and NOD-like receptors (NLRs).…”