Research Article
Telomere Elongation and Mismatch Repair Deficiency Distinguish MSI Colorectal Cancer Cell Lines
Rajasekhar Moka*
,
Shreya Upadhya
Issue:
Volume 13, Issue 2, June 2025
Pages:
23-29
Received:
17 April 2025
Accepted:
29 April 2025
Published:
29 May 2025
Abstract: Microsatellite instability (MSI) is a hallmark of mismatch repair (MMR) deficiency and characterizes a distinct subset of colorectal cancers (CRC). In parallel, telomere length dynamics have emerged as important contributors to genomic stability and tumorigenesis. However, the relationship between MSI status, MMR protein expression, and telomere maintenance remains poorly defined. This study aimed to investigate the association between MSI status and telomere length in CRC cell lines and to evaluate the expression of key MMR proteins (MLH1, MSH2, MSH6, PMS2) to elucidate molecular differences between MSI and microsatellite stable (MSS) phenotypes. A panel of CRC cell lines with known MSI and MSS statuses was used. Telomere length was quantified using real-time quantitative PCR (qPCR) based on the T/S ratio method. MSI status was confirmed via PCR using mononucleotide repeat markers. Western blotting was performed to assess protein expressions of MLH1, MSH2, MSH6, and PMS2. β-actin served as a loading control. qPCR analysis revealed that MSI cell lines exhibited significantly longer telomeres compared to MSS lines (P < 0.05). Western blot results showed reduced or absent expression of MLH1 and PMS2 in MSI cell lines, confirming MMR deficiency. In contrast, MSS cell lines maintained normal expression of all tested MMR proteins. These findings suggest a link between defective MMR function and altered telomere dynamics in MSI-CRC. MSI CRC cell lines exhibit telomere elongation and loss of key MMR proteins, highlighting distinct molecular features compared to MSS counterparts. These insights may inform future strategies for personalized CRC diagnostics and therapeutics, particularly in the context of telomere-targeted or immunomodulatory treatments.
Abstract: Microsatellite instability (MSI) is a hallmark of mismatch repair (MMR) deficiency and characterizes a distinct subset of colorectal cancers (CRC). In parallel, telomere length dynamics have emerged as important contributors to genomic stability and tumorigenesis. However, the relationship between MSI status, MMR protein expression, and telomere ma...
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Research Article
Crocin and Flavocoxid Inhibit Tumor Growth, Alter Cytokine Levels of (IL-10/Tnf-α), and Promote Caspase-Induced Apoptosis, and Doxorubicin Efficacy
Issue:
Volume 13, Issue 2, June 2025
Pages:
30-45
Received:
28 August 2024
Accepted:
18 September 2024
Published:
6 June 2025
DOI:
10.11648/j.crj.20251302.12
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Abstract: Background: We assessed the differential sole and Doxorubicin-(Doxo)-combined chemotherapy of the phytomedicines Crocin and Flavocoxid-(flvcox), against the-mouse-Ehrlich-Ascites-Carcinoma-solid-tumor-model-(EAC). We further identified the underlying-molecular mechanisms of actions, interrelations of probed signals, as well as the relative-potency among all used drug modalities. Methods: Functional studies evaluated tumor-burden, animal-survival, serum/tumor redox-status, and levels of key-effectors coherent with tumorigenesis, inflammation, and host-immunity, namely (serum IL-10 and TNF-α) and with tumor-apoptosis (Caspase-3-expression). Furthermore, histopathological examinations were performed to envisage the associated structural changes. Results: EAC-bearing mice had significantly raised serum-TNF-α and tumor lipid-peroxide (MDA) levels, but lower serum IL-10-levels and total serum antioxidant-capacity-(TAC), thereby showing animal-fatalities after-3-weeks. Crocin administration significantly-shrank tumor-mass by (50%), -reduced tumor lipid-peroxide-(MDA) and serum-TNF-α levels; but raised serum-IL-10, TAC and tumor-caspase-3 levels; ultimately augmenting animal survival by (79%). Flvcox had weaker survival-effects (44%) than that of crocin. Correlation studies showed IL-10, contrary to TNF-α to boost animal-survival, and suppress tumor-size. Tumor caspase-3 levels augmented both animal-survival and the TAC-level, while opposed tumor-weight and tumor-MDA levels. Besides, tumor oxidative-stress boosted tumor growth, and reduced caspase-3 levels, thereby worsening animal survival. Histopathology analyses confirmed functional studies. Conclusions: 1)- The study reveals that Doxo confers superior cytotoxicity but inferior cytokine-balance, redox-status and animal-rescuing profiles; 2)- Crocin and Flvcox elicit prominent sole- and combined-cytotoxicity, and animal-rescuing potentials, by restoring the disrupted-balance of the cytokines (IL-10/TNF-α), optimizing serum/tumor redox-potentials and accelerating tumor-cell apoptosis; 3)- Cross-talk was evidently documented among (key-cytokines), (tumor-burden), (redox-status), and (tumor-apoptosis), in a manner that dictates the efficacy of sole (or) mutual-therapy, and their influence on animal-survival in response to cancer.
Abstract: Background: We assessed the differential sole and Doxorubicin-(Doxo)-combined chemotherapy of the phytomedicines Crocin and Flavocoxid-(flvcox), against the-mouse-Ehrlich-Ascites-Carcinoma-solid-tumor-model-(EAC). We further identified the underlying-molecular mechanisms of actions, interrelations of probed signals, as well as the relative-potency ...
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