scholarly journals In Vitro Evaluation of Anti-Colon Cancer Potential of Crude Extracts of Fucoidan Obtained from Sargassum Glaucescens Pretreated by Compressional-Puffing

2020 ◽  
Vol 10 (9) ◽  
pp. 3058
Author(s):  
Wei-Cheng Shiao ◽  
Chia-Hung Kuo ◽  
Yung-Hsiang Tsai ◽  
Shu-Ling Hsieh ◽  
Ai-Wei Kuan ◽  
...  

Fucoidans constitute a family of fucose-rich sulfated polysaccharides, which possess multiple characteristics, including antioxidant, antitumor, antivirus, anticoagulant, and anti-inflammatory properties. In addition, the incidence of colon cancer has risen rapidly worldwide. In the present study, fucoidan extracts were extracted from the Sargassum glaucescens (SG) pretreated by compressional-puffing, and four fucoidans (SG1-SG4) were obtained with different puffing conditions. It was found that SG4 possessed the highest extraction yield, relatively high cytotoxicity against human colon carcinoma HT-29 cells, and relatively low cytotoxicity to normal cells, as compared to the other extracted fucoidans. Moreover, SG4 caused cell cycle arrest of HT-29 cells at sub-G1, S, and G2/M phases. SG4 also induced HT-29 cellular apoptosis, as evidenced by the loss of mitochondrial membrane potential (MMP), increased cytochrome c release, activation of caspase-9 and -3, increased DNA fragmentation, and increased early and late apoptotic cells visualized by annexin V/propidium iodide (PI) assay. Additional biological experiments revealed that the Akt/mammalian target of rapamycin (mTOR)/S6 pathway is involved in SG4-induced apoptosis of HT-29 cells. These results clearly indicate that SG4 showed anti-colon cancer potential via the induction of cell cycle arrest and apoptosis, and thus may have a possible application as an adjuvant therapeutic agent in colon cancer treatment.

Foods ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 300 ◽  
Author(s):  
Hanaa Zbakh ◽  
Eva Zubía ◽  
Carolina De Los Reyes ◽  
José M. Calderón-Montaño ◽  
Virginia Motilva

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.


Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4139 ◽  
Author(s):  
Shahinaz Mahajna ◽  
Sleman Kadan ◽  
Zipora Tietel ◽  
Bashar Saad ◽  
Said Khasib ◽  
...  

Naturally derived drugs and plant-based products are attractive commodities that are being explored for cancer treatment. This in vitro study aimed to investigate the role of Hypericum triquetrifolium (50% ethanol: 50% water) extract (HTE) treatment on apoptosis, cell cycle modulation, and cell cycle arrest in human colon cancer cell line (HCT-116). HTE induced cell death via an apoptotic process, as assayed by an Annexin V-Cy3 assay. Exposing HCT-116 cells to 0.064, 0.125, 0.25, and 0.5 mg/mL of HTE for 24 h led to 50 ± 9%, 71.6 ± 8%, 85 ± 5%, and 96 ± 1.5% apoptotic cells, respectively. HCT-116 cells treated with 0.25 and 0.5 mg/mL HTE for 3 h resulted in 38.9 ± 1.5% and 57.2 ± 3% cleavage of caspase-3-specific substrate, respectively. RT-PCR analysis revealed that the HTE extract had no effect on mRNA levels of Apaf-1 and NOXA. Moreover, the addition of 0.125 mg/mL and 0.25 mg/mL HTE for 24 h was clearly shown to attenuate the cell cycle progression machinery in HCT-116 cells. GC/MS analysis of the extract identified 21 phytochemicals that are known as apoptosis inducers and cell cycle arrest agents. All the compounds detected are novel in H. triquetrifolium. These results suggest that HTE-induced apoptosis of human colon cells is mediated primarily through the caspase-dependent pathway. Thus, HTE appears to be a potent therapeutic agent for colon cancer treatment.


Cells ◽  
2018 ◽  
Vol 7 (7) ◽  
pp. 81 ◽  
Author(s):  
Eric Smith ◽  
Helen Palethorpe ◽  
Yoko Tomita ◽  
Jinxin Pei ◽  
Amanda Townsend ◽  
...  

Aquaporin-1 (AQP1), a transmembrane pore-forming molecule, facilitates the rapid movement of water and small solutes across cell membranes. We have previously shown that bacopaside II, an extract from the medicinal herb Bacopa monnieri, blocks the AQP1 water channel and impairs migration of cells that express AQP1. The aim of this study was to further elucidate the anti-tumour potential of bacopaside II in colon cancer cells. Expression of AQP1 in HT-29, SW480, SW620 and HCT116 was determined by quantitative PCR and western immunoblot. Cells were treated with bacopaside II, and morphology, growth, autophagy, cell cycle and apoptosis assessed by time-lapse microscopy, crystal violet, acridine orange, propidium iodide (PI) and annexin V/PI staining respectively. AQP1 expression was significantly higher in HT-29 than SW480, SW620 and HCT116. Bacopaside II significantly reduced growth at ≥20 µM for HT-29 and ≥15 µM for SW480, SW620 and HCT116. Inhibition of HT-29 at 20 µM was primarily mediated by G0/G1 cell cycle arrest, and at 30 µM by G2/M arrest and apoptosis. Inhibition of SW480, SW620 and HCT116 at ≥15 µM was mediated by G2/M arrest and apoptosis. These results are the first to show that bacopaside II inhibits colon cancer cell growth by inducing cell cycle arrest and apoptosis.


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