MPT0B169 and MPT0B002, New Tubulin Inhibitors, Induce Growth Inhibition, G2/M Cell Cycle Arrest, and Apoptosis in Human Colorectal Cancer Cells

Pharmacology ◽  
2018 ◽  
Vol 102 (5-6) ◽  
pp. 262-271 ◽  
Author(s):  
Chih-Hsin Lee ◽  
Yuan-Feng Lin ◽  
Yen-Chou Chen ◽  
Shuit-Mun Wong ◽  
Shu-Hui Juan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Cyclin B1 ◽  
M Cell ◽  
Apoptotic Pathway ◽  
Tubulin Inhibitors ◽  
Ht29 Cells

We previously synthesized new tubulin inhibitors, MPT0B169 and MPT0B002, which induced growth inhibition and apoptosis in leukemia cells. However, their effects on solid tumor cells have not been determined. In this study, we investigated the effects of MPT0B169 and MPT0B002 on glioblastoma, breast, lung, and colorectal cancer (CRC) cell lines. A cell viability analysis showed that MPT0B169 and MPT0B002 were more effective in inhibiting the proliferation of COLO205 and HT29 CRC cells than U87MG and GBM8401 glioblastoma, MCF-7 and MDA-MB-231 breast cancer, and A549 lung cancer cells. MPT0B169 and MPT0B002 inhibited growth of COLO205 and HT29 cells in dose- and time-dependent manners. A colony-formation assay confirmed the growth inhibitory effects of MPT0B169 and MPT0B002 on COLO205 and HT29 cells. MPT0B169 and MPT0B002 disrupted tubulin polymerization and arrested the cell cycle at the G2/M phase, with a concomitant increase of the cyclin B1 level. MPT0B169 and MPT0B002 induced apoptosis, accompanied by induction of the intrinsic apoptotic pathway, as shown by a reduction in the caspase-9 level and increases in cleaved caspase-3 and cleaved PARP. These results suggest that MPT0B169 and MPT0B002, new tubulin inhibitors, induced growth inhibition, G2/M arrest, and apoptosis in COLO205 and HT29 cells, and they could potentially be anticancer agents for CRC cells.

Antiproliferative effects of triterpenoidal derivatives, obtained from the marine sponge Siphonochalina sp., on human hepatic and colorectal cancer cells

2016 ◽  
Vol 71 (1-2) ◽  
pp. 29-35 ◽  
Author(s):  
Ahmed Abdel-Lateff ◽  
Ahmed M. Al-Abd ◽  
Abdulrahman M. Alahdal ◽  
Walied M. Alarif ◽  
Seif-Eldin N. Ayyad ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Cyclin B1 ◽  
Moderate Activity ◽  
Antiproliferative Effects ◽  
Cycle Arrest ◽  
Colorectal Cancer Cells ◽  
Ht 29

Abstract Three triterpenoidal derivatives [Sipholenol A (1), sipholenol L (2) and sipholenone A (3)] were isolated from the Red Sea sponge Siphonochalina sp. The structures were determined based on spectroscopic measurements (NMR, UV, IR and MS). The isolated compounds were evaluated for their cytotoxic activity against three cancer cell lines; HepG2, Caco-2 and HT-29. Moreover, the effects of these metabolites on cell cycle progression as well as cell cycle regulating proteins were assessed. Compounds 1, 2 and 3 showed moderate activity against HepG2 cells with IC50 values of 17.18 ± 1.18, 24.01 ± 0.59 and 35.06 ± 1.10 μM, respectively. Compounds 1 and 2 exerted a considerable antiproliferative effect with IC50 values of 4.80 ± 0.18 and 26.64 ± 0.30 μM, respectively, against Caco-2 cells. Finally, 1 and 2 exhibited antiproliferative activity against colorectal cancer cells (HT-29) with IC50 values of 24.65 ± 0.80 and 4.48 ± 0.1 μM, respectively. Cell cycle analysis indicated that these compounds induced cell cycle arrest particularly in G0/G1 and S phases. Furthermore, the triterpenoids increased the expression of cyclin-B1, cyclin-D1 and cleaved caspase-3, as determined by immunofluorescence, indicating an important role of apoptosis in cell death induced by these compounds.

scholarly journals Antitumor Effects of N-Butylidenephthalide Encapsulated in Lipopolyplexs in Colorectal Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2394 ◽  
Author(s):  
Kai-Fu Chang ◽  
Jinghua Tsai Chang ◽  
Xiao-Fan Huang ◽  
Yu-Ling Lin ◽  
Kuang-Wen Liao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Drug Carrier ◽  
Cyclin B1 ◽  
Cell Uptake ◽  
Antitumor Effects ◽  
Cycle Arrest ◽  
Apoptosis Pathways ◽  
Fas L

Colorectal cancer (CRC) is the third most common type of cancer and the second most common cause of cancer-related death in the world. N-Butylidenephthalide (BP), a natural compound, inhibits several cancers, such as hepatoma, brain tumor and colon cancer. However, due to the unstable structure, the activity of BP is quickly lost after dissolution in an aqueous solution. A polycationic liposomal polyethylenimine and polyethylene glycol complex (LPPC), a new drug carrier, encapsulates both hydrophobic and hydrophilic compounds, maintains the activity of the compound, and increases uptake of cancer cells. The purpose of this study is to investigate the antitumor effects and protection of BP encapsulated in LPPC in CRC cells. The LPPC encapsulation protected BP activity, increased the cytotoxicity of BP and enhanced cell uptake through clathrin-mediated endocytosis. Moreover, the BP/LPPC-regulated the expression of the p21 protein and cell cycle-related proteins (CDK4, Cyclin B1 and Cyclin D1), resulting in an increase in the population of cells in the G0/G1 and subG1 phases. BP/LPPC induced cell apoptosis by activating the extrinsic (Fas, Fas-L and Caspase-8) and intrinsic (Bax and Caspase-9) apoptosis pathways. Additionally, BP/LPPC combined with 5-FU synergistically inhibited the growth of HT-29 cells. In conclusion, LPPC enhanced the antitumor activity and cellular uptake of BP, and the BP/LPPC complex induced cell cycle arrest and apoptosis, thereby causing death. These findings suggest the putative use of BP/LPPC as an adjuvant cytotoxic agent for colorectal cancer.

scholarly journals Fisetin induces G2/M phase cell cycle arrest by inactivating cdc25C-cdc2 via ATM-Chk1/2 activation in human endometrial cancer cells

2015 ◽  
Vol 10 (2) ◽  
pp. 279 ◽  
Author(s):  
Zan-Ying Wang ◽  
Wen-Qiong Liu ◽  
Si’e Wang ◽  
Zeng-Tao Wei
Keyword(s):  
Cell Cycle ◽  
Endometrial Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Cyclin B1 ◽  
Phase Cell ◽  
M Cell ◽  
Proliferative Effect ◽  
Cycle Arrest ◽  
M Phase

<p>Endometrial cancer is one of the most prevalent gynaecological malignancies where, currently available therapeutic options remain limited. Recently phytochemicals are exploited for their efficiency in cancer therapy. The present study investigates the anti-proliferative effect of fisetin, a flavonoid on human endometrial cancer cells (KLE and Hec1 A). Fisetin (20-100 µM) effectively reduced the viability of Hec1 A and KLE cells and potentially altered the cell population at G2/M stage. Expression levels of the cell cycle proteins (cyclin B1, p-Cdc2, p-Cdc25C, p-Chk1, Chk2, p-ATM, cyclin B1, H2AX, p21 and p27) were analyzed. Fisetin suppressed cyclin B1 expression and caused inactiva-tion of Cdc25C and Cdc2 by increasing their phosphorylation levels and further activated ATM, Chk1 and Chk2. Increased levels of p21 and p27 were observed as well. These results suggest that fisetin induced G2/M cell cycle arrest via inactivating Cdc25c and Cdc2 through activation of ATM, Chk1 and Chk2.</p><p> </p><p> </p>

scholarly journals Inhibiting EMT, stemness and cell cycle involved in baicalin-induced growth inhibition and apoptosis in colorectal cancer cells

2020 ◽  
Vol 11 (8) ◽  
pp. 2303-2317 ◽  
Author(s):  
Bolin Yang ◽  
Huiru Bai ◽  
Yunli Sa ◽  
Ping Zhu ◽  
Ping Liu
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Colorectal Cancer Cells
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