scholarly journals DNA damage signaling is activated during cancer progression in human colorectal carcinoma

2010 ◽  
Vol 9 (3) ◽  
pp. 245-251 ◽  
Author(s):  
Kazuhito Oka ◽  
Toshiki Tanaka ◽  
Tadahiko Enoki ◽  
Koichi Yoshimura ◽  
Mako Ohshima ◽  
...  
Keyword(s):  
Dna Damage ◽  
Colorectal Carcinoma ◽  
Cancer Progression ◽  
Dna Damage Signaling ◽  
Human Colorectal Carcinoma

scholarly journals Antitumor Mechanism of Hydroxycamptothecin via the Metabolic Perturbation of Ribonucleotide and Deoxyribonucleotide in Human Colorectal Carcinoma Cells

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4902
Author(s):  
Yan Li ◽  
Wendi Luo ◽  
Huixia Zhang ◽  
Caiyun Wang ◽  
Caiyuan Yu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Colorectal Carcinoma ◽  
Dna Synthesis ◽  
Topoisomerase I ◽  
De Novo ◽  
Nucleotide Metabolism ◽  
Dependent Manner ◽  
Anticancer Effect ◽  
Nucleotide Synthesis ◽  
Human Colorectal Carcinoma

Hydroxycamptothecin (SN38) is a natural plant extract isolated from Camptotheca acuminate. It has a broad spectrum of anticancer activity through inhibition of DNA topoisomerase I, which could affect DNA synthesis and lead to DNA damage. Thus, the action of SN38 against cancers could inevitably affect endogenous levels of ribonucleotide (RNs) and deoxyribonucleotide (dRNs) that play critical roles in many biological processes, especially in DNA synthesis and repair. However, the exact impact of SN38 on RNs and dRNs is yet to be fully elucidated. In this study, we evaluated the anticancer effect and associated mechanism of SN38 in human colorectal carcinoma HCT 116 cells. As a result, SN38 could decrease the cell viability and induce DNA damage in a concentration-dependent manner. Furthermore, cell cycle arrest and intracellular nucleotide metabolism were perturbed due to DNA damage response, of which ATP, UTP, dATP, and TTP may be the critical metabolites during the whole process. Combined with the expression of deoxyribonucleoside triphosphates synthesis enzymes, our results demonstrated that the alteration and imbalance of deoxyribonucleoside triphosphates caused by SN38 was mainly due to the de novo nucleotide synthesis at 24 h, and subsequently the salvage pathways at 48 h. The unique features of SN38 suggested that it might be recommended as an effective supplementary drug with an anticancer effect.

Fatty Acid Profile and In Vitro Anticancer Activity of Two Marine Sponge- Associated Bacteria

2020 ◽  
Vol 16 (9) ◽  
pp. 1273-1280
Author(s):  
Giuseppina Tommonaro ◽  
Ali M. El-Hagrassi ◽  
Walid Fayad ◽  
Carmine Iodice ◽  
Kamel H. Shaker ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Colorectal Carcinoma ◽  
Cell Line ◽  
Marine Sponge ◽  
Hct116 Cell ◽  
Associated Bacteria ◽  
Sponge Associated Bacteria ◽  
Human Colorectal Carcinoma

Background: Colorectal cancer represents one of the prominent causes of mortality worldwide in men and women. The objective of this study was to search for new potential anticancer compounds, both in prevention and treatment of colorectal cancer. The anticancer potential of marine bacterial extracts against Human colorectal carcinoma cell line (HCT116) was evaluated as well as the partial identification of bioactive metabolites. Methods: All bacterial extracts were tested for their cytotoxicity against HCT116 cell line by means of MTT assay. The highly cytotoxic dichloromethane extracts of marine sponge-associated bacteria Vibrio sp. and Bacillus sp. were analyzed by GC-MS. Results: Two fractions, Vib3 and Bac3, exhibited a very interesting cytotoxicity against human colorectal carcinoma (HCT116) cell line, with a percentage of cytotoxicity of 96.04 % and 29.48 %, respectively. Discussion: The GC-MS analysis revealed the presence of two major fatty acids, palmitic and oleic acids, in Vib3 fraction and fatty acid esters and phenolic compounds in Bac3 fraction. Conclusion: Based on previous literature, it may be hypothesized that the anticancer activity of bacterial extracts could be, at least partially, to the fatty acids fraction.

scholarly journals PRL3 induces polypoid giant cancer cells eliminated by PRL3-zumab to reduce tumor relapse

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Min Thura ◽  
Zu Ye ◽  
Abdul Qader Al-Aidaroos ◽  
Qiancheng Xiong ◽  
Jun Yi Ong ◽  
...  
Keyword(s):  
Dna Damage ◽  
Stem Cell ◽  
Cancer Cells ◽  
Embryonic Stem ◽  
Genotoxic Stress ◽  
Stem Cell Markers ◽  
Tumor Removal ◽  
Primary Tumors ◽  
Tumor Relapse ◽  
Dna Damage Signaling

AbstractPRL3, a unique oncotarget, is specifically overexpressed in 80.6% of cancers. In 2003, we reported that PRL3 promotes cell migration, invasion, and metastasis. Herein, firstly, we show that PRL3 induces Polyploid Giant Cancer Cells (PGCCs) formation. PGCCs constitute stem cell-like pools to facilitate cell survival, chemo-resistance, and tumor relapse. The correlations between PRL3 overexpression and PGCCs attributes raised possibilities that PRL3 could be involved in PGCCs formation. Secondly, we show that PRL3+ PGCCs co-express the embryonic stem cell markers SOX2 and OCT4 and arise mainly due to incomplete cytokinesis despite extensive DNA damage. Thirdly, we reveal that PRL3+ PGCCs tolerate prolonged chemotherapy-induced genotoxic stress via suppression of the pro-apoptotic ATM DNA damage-signaling pathway. Fourthly, we demonstrated PRL3-zumab, a First-in-Class humanized antibody drug against PRL3 oncotarget, could reduce tumor relapse in ‘tumor removal’ animal model. Finally, we confirmed that PGCCs were enriched in relapse tumors versus primary tumors. PRL3-zumab has been approved for Phase 2 clinical trials in Singapore, US, and China to block all solid tumors. This study further showed PRL3-zumab could potentially serve an ‘Adjuvant Immunotherapy’ after tumor removal surgery to eliminate PRL3+ PGCC stem-like cells, preventing metastasis and relapse.

scholarly journals Germ granule dysfunction is a hallmark and mirror of Piwi mutant sterility

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Maya Spichal ◽  
Bree Heestand ◽  
Katherine Kretovich Billmyre ◽  
Stephen Frenk ◽  
Craig C. Mello ◽  
...  
Keyword(s):  
Dna Damage ◽  
Genomic Instability ◽  
Environmental Restoration ◽  
Related Gene ◽  
C Elegans ◽  
Dna Damage Signaling ◽  
Multiple Phenotypes ◽  
Granule Structure ◽  
Germ Granules ◽  
Late Generation

AbstractIn several species, Piwi/piRNA genome silencing defects cause immediate sterility that correlates with transposon expression and transposon-induced genomic instability. In C. elegans, mutations in the Piwi-related gene (prg-1) and other piRNA deficient mutants cause a transgenerational decline in fertility over a period of several generations. Here we show that the sterility of late generation piRNA mutants correlates poorly with increases in DNA damage signaling. Instead, sterile individuals consistently exhibit altered perinuclear germ granules. We show that disruption of germ granules does not activate transposon expression but induces multiple phenotypes found in sterile prg-1 pathway mutants. Furthermore, loss of the germ granule component pgl-1 enhances prg-1 mutant infertility. Environmental restoration of germ granule function for sterile pgl-1 mutants restores their fertility. We propose that Piwi mutant sterility is a reproductive arrest phenotype that is characterized by perturbed germ granule structure and is phenocopied by germ granule dysfunction, independent of genomic instability.

scholarly journals Platinum Complexes in Colorectal Cancer and Other Solid Tumors

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2073
Author(s):  
Beate Köberle ◽  
Sarah Schoch
Keyword(s):  
Colorectal Cancer ◽  
Dna Damage ◽  
Dna Repair ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Platinum Complexes ◽  
Dna Lesions ◽  
Dna Damage Signaling ◽  
Repair Mechanisms ◽  
P53 Inactivation

Cisplatin is one of the most commonly used drugs for the treatment of various solid neoplasms, including testicular, lung, ovarian, head and neck, and bladder cancers. Unfortunately, the therapeutic efficacy of cisplatin against colorectal cancer is poor. Various mechanisms appear to contribute to cisplatin resistance in cancer cells, including reduced drug accumulation, enhanced drug detoxification, modulation of DNA repair mechanisms, and finally alterations in cisplatin DNA damage signaling preventing apoptosis in cancer cells. Regarding colorectal cancer, defects in mismatch repair and altered p53-mediated DNA damage signaling are the main factors controlling the resistance phenotype. In particular, p53 inactivation appears to be associated with chemoresistance and poor prognosis. To overcome resistance in cancers, several strategies can be envisaged. Improved cisplatin analogues, which retain activity in resistant cancer, might be applied. Targeting p53-mediated DNA damage signaling provides another therapeutic strategy to circumvent cisplatin resistance. This review provides an overview on the DNA repair pathways involved in the processing of cisplatin damage and will describe signal transduction from cisplatin DNA lesions, with special attention given to colorectal cancer cells. Furthermore, examples for improved platinum compounds and biochemical modulators of cisplatin DNA damage signaling will be presented in the context of colon cancer therapy.

Sign in / Sign up

Export Citation Format

Share Document