scholarly journals Structural Optimization and Improving Antitumor Potential of Moreollic Acid from Gamboge

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 482
Author(s):  
Li-Zhi Cheng ◽  
Dan-Ling Huang ◽  
Min Liao ◽  
Ke-Ming Li ◽  
Zhao-Qiu Wu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Human Colon ◽  
Antitumor Activities ◽  
Human Colon Cancer ◽  
Cycle Progression ◽  
Antitumor Potential ◽  
Ic50 Values ◽  
Novel Structures

Moreollic acid, a caged-tetraprenylated xanthone from Gamboge, has been indicated as a potent antitumor molecule. In the present study, a series of moreollic acid derivatives with novel structures were designed and synthesized, and their antitumor activities were determined in multifarious cell lines. The preliminary screening results showed that all synthesized compounds selectively inhibited human colon cancer cell proliferation. TH12-10, with an IC50 of 0.83, 1.10, and 0.79 μM against HCT116, DLD1, and SW620, respectively, was selected for further antitumor mechanism studies. Results revealed that TH12-10 effectively inhibited cell proliferation by blocking cell-cycle progression from G1 to S. Besides, the apparent structure–activity relationships of target compounds were discussed. To summarize, a series of moreollic acid derivatives were discovered to possess satisfactory antitumor potentials. Among them, TH12-10 displays the highest antitumor activities against human colon cancer cells, in which the IC50 values in DLD1 and SW620 are lower than that of 5-fluorouracil.

scholarly journals Quantitative analysis of the level of p53 and p21(WAF1) mRNA in human colon cancer HT-29 cells treated with inositol hexaphosphate.

2006 ◽  
Vol 53 (2) ◽  
pp. 349-356 ◽  
Author(s):  
Ludmiła Weglarz ◽  
Izabela Molin ◽  
Arkadiusz Orchel ◽  
Beata Parfiniewicz ◽  
Zofia Dzierzewicz
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Cycle Progression ◽  
Mrna Level ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Cycle Progression ◽  
Inositol Hexaphosphate ◽  
P21 Waf1 ◽  
Ht 29

The aim of this study was to analyze the molecular mechanism of inositol hexaphosphate (InsP(6)) action through which it may inhibit proliferation of colon cancer cells and cell cycle progression. A kinetic study of p53 and p21(WAF1) mRNA increase was performed on human colon cancer HT-29 cells after treatment with 1, 5 and 10 mM InsP(6) for 6, 12, 24 and 48 h. Real-time-QPCR based on TaqMan methodology was applied to analyze quantitatively the transcript levels of these genes. The transcription of beta-actin and GAPDH genes was assessed in parallel to select the control gene with least variability. The 2(-Delta Delta Ct) method was used to analyze the relative changes in gene transcription. InsP(6) stimulated p53 and p21(WAF1) expression at the mRNA level, with the highest increase in p21(WAF1) mRNA occurring at 24 h, i.e., following the highest increase in p53 mRNA observed at 12 h. Based on these studies it may be concluded that the ability of InsP(6) to arrest the cell cycle may be mediated by the transcriptional up-regulation of the p53-responsive p21(WAF1) gene.

scholarly journals Radiation-Stimulated ERK1/2 and JNK1/2 Signaling can Promote Cell Cycle Progression in Human Colon Cancer Cells

Cell Cycle ◽  
2005 ◽  
Vol 4 (3) ◽  
pp. 456-464 ◽  
Author(s):  
Ruben W. Caron ◽  
Adly Yacoub ◽  
Clint Mitchell ◽  
Xiaoyu Zhu ◽  
Young Hong ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Cycle Progression ◽  
Promote Cell Cycle Progression ◽  
Human Colon Cancer Cells

scholarly journals Olaparib-mediated enhancement of 5-fluorouracil cytotoxicity in mismatch repair deficient colorectal cancer cells

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Helena de Castro e Gloria ◽  
Laura Jesuíno Nogueira ◽  
Patrícia Bencke Grudzinski ◽  
Paola Victória da Costa Ghignatti ◽  
Temenouga Nikolova Guecheva ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Mismatch Repair ◽  
Cell Cycle Progression ◽  
Combined Therapy ◽  
Combined Treatment ◽  
Human Colon ◽  
Human Colon Cancer

Abstract Background The advances in colorectal cancer (CRC) treatment include the identification of deficiencies in Mismatch Repair (MMR) pathway to predict the benefit of adjuvant 5-fluorouracil (5-FU) and oxaliplatin for stage II CRC and immunotherapy. Defective MMR contributes to chemoresistance in CRC. A growing body of evidence supports the role of Poly-(ADP-ribose) polymerase (PARP) inhibitors, such as Olaparib, in the treatment of different subsets of cancer beyond the tumors with homologous recombination deficiencies. In this work we evaluated the effect of Olaparib on 5-FU cytotoxicity in MMR-deficient and proficient CRC cells and the mechanisms involved. Methods Human colon cancer cell lines, proficient (HT29) and deficient (HCT116) in MMR, were treated with 5-FU and Olaparib. Cytotoxicity was assessed by MTT and clonogenic assays, apoptosis induction and cell cycle progression by flow cytometry, DNA damage by comet assay. Adhesion and transwell migration assays were also performed. Results Our results showed enhancement of the 5-FU citotoxicity by Olaparib in MMR-deficient HCT116 colon cancer cells. Moreover, the combined treatment with Olaparib and 5-FU induced G2/M arrest, apoptosis and polyploidy in these cells. In MMR proficient HT29 cells, the Olaparib alone reduced clonogenic survival, induced DNA damage accumulation and decreased the adhesion and migration capacities. Conclusion Our results suggest benefits of Olaparib inclusion in CRC treatment, as combination with 5-FU for MMR deficient CRC and as monotherapy for MMR proficient CRC. Thus, combined therapy with Olaparib could be a strategy to overcome 5-FU chemotherapeutic resistance in MMR-deficient CRC.

Cellular mechanisms involved in the melatonin inhibition of HT-29 human colon cancer cell proliferation in culture

2007 ◽  
Vol 43 (2) ◽  
pp. 195-205 ◽  
Author(s):  
Ana García-Navarro ◽  
Cristina González-Puga ◽  
Germaine Escames ◽  
Luis C. López ◽  
Ana López ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Human Colon ◽  
Colon Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Human Colon Cancer Cell ◽  
Cellular Mechanisms ◽  
Human Colon Cancer ◽  
Ht 29
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