Different Roles of Apoptosis and Autophagy in the Development of Human Colorectal Cancer

Orlandi, Giulia; Roncucci, Luca; Carnevale, Gianluca; Sena, Paola

doi:10.3390/ijms241210201

Cited by 16 publications

(4 citation statements)

References 114 publications

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“…These findings suggest that these associated functions may be related to ferroptosis and cuproptosis. Current reports indicate that the Nod-like receptor (NLR) signaling pathway, fructose and mannose metabolism, and apoptosis have inhibitory effects on tumor cells, consistent with the conclusions obtained from our gene set variation analysis [51–53].…”

Section: Discussionsupporting

confidence: 90%

Identification of cuproptosis and ferroptosis-related subtypes and development of a prognostic signature in colon cancer

He,

Liu,

Jiang

2024

Preprint

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Colon cancer, as a highly prevalent malignant tumor globally, poses a significant threat to human health. In recent years, ferroptosis and cuproptosis, as two novel forms of cell death, have attracted widespread attention for their potential roles in the development and treatment of colon cancer. However, the investigation into the subtypes and their impact on the survival of colon cancer patients remains understudied. In this study, utilizing data from TCGA and GEO databases, we examined the expression differences of ferroptosis and cuproptosis-related genes in colon cancer and identified two subtypes. Through functional analysis and bioinformatics methods, we elucidated pathway differences and biological characteristics between these two subtypes. By leveraging differential genes between the two subtypes, we constructed a prognostic model using univariate Cox regression and multivariate Cox regression analysis as well as LASSO regression analysis. Further survival analysis and receiver operating characteristic curve analysis demonstrated the model’s high accuracy. To enhance its clinical utility, we evaluated the clinical significance of the model and constructed a nomogram, significantly improving the predictive ability of the model and providing a new tool for prognostic assessment of colon cancer patients. Subsequently, through immune-related analysis, we revealed differences in immune cell infiltration and immune function between high- and low-risk groups. Further analysis of the relationship between the model and immune cells and functions revealed potential therapeutic targets. Drug sensitivity analysis revealed associations between the expression of model-related genes and drug sensitivity, suggesting their involvement in tumor resistance through certain mechanisms. AZD8055_1059, Bortezomib_1191, Dihydrorotenone_1827, and MG-132_1862 were more sensitive in the high-risk group. Finally, we analyzed differential expression of model-related genes between tumor tissues and normal tissues, validated through real-time quantitative PCR. In summary, our study provides a relatively accurate prognostic tool for colon cancer patients, offering guidance for treatment selection and indicating the potential of immunotherapy in colon cancer.

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Section: Discussionsupporting

confidence: 90%

Identification of cuproptosis and ferroptosis-related subtypes and development of a prognostic signature in colon cancer

He,

Liu,

Jiang

2024

Preprint

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“…p62 and LC3B serve as autophagy markers. The p62 protein contains multiple domains and acts as an adaptor between the autophagosome and substrate, playing a crucial role in regulating autophagy [36][37][38] . However, LC3B-I undergoes lipidation, similar to ubiquitination, resulting in the formation of lipidated LC3B-II that attaches to membranes and functions as a structural protein within autophagosomes.…”

Section: Discussionmentioning

confidence: 99%

Caffeic acid phenethyl ester promotes oxaliplatin sensitization in colon cancer by inhibiting autophagy

Xing,

Liu,

Wang

et al. 2024

Sci Rep

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Colon cancer ranks as the third most prevalent form of cancer globally, with chemotherapy remaining the primary treatment modality. To mitigate drug resistance and minimize adverse effects associated with chemotherapy, selection of appropriate adjuvants assumes paramount importance. Caffeic acid phenethyl ester (CAPE), a naturally occurring compound derived from propolis, exhibits a diverse array of biological activities. We observed that the addition of CAPE significantly augmented the drug sensitivity of colon cancer cells to oxaliplatin. In SW480 and HCT116 cells, oxaliplatin combined with 10 µM CAPE reduced the IC50 of oxaliplatin from 14.24 ± 1.03 and 84.16 ± 3.02 µM to 2.11 ± 0.15 and 3.92 ± 0.17 µM, respectively. We then used proteomics to detect differentially expressed proteins in CAPE-treated SW480 cells and found that the main proteins showing changes in expression after CAPE treatment were p62 (SQSTM1) and LC3B (MAP1LC3B). Gene ontology analysis revealed that CAPE exerted antitumor and chemotherapy-sensitization effects through the autophagy pathway. We subsequently verified the differentially expressed proteins using immunoblotting. Simultaneously, the autophagy inhibitor bafilomycin A1 and the mCherry-EGFP-LC3 reporter gene were used as controls to detect the effect of CAPE on autophagy levels. Collectively, the results indicate that CAPE may exert antitumor and chemotherapy-sensitizing effects by inhibiting autophagy, offering novel insights for the development of potential chemosensitizing agents.

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“…Apoptosis plays a crucial role in regulating cell growth and proliferation, thereby preventing the development of cancer [57]. In CRC, apoptosis serves as a natural cellular mechanism to control excessive cell division and maintain tissue homeostasis [58].…”

Section: Fisetin Suppresses the Growth Of Cancer Cells By Promoting A...mentioning

confidence: 99%

A Narrative Review on Therapeutic Potential of Fisetin in Colorectal Cancer: Focusing on apoptosis and biochemical processes

Zamanian,

Taheri,

Ramadan

et al. 2024

Preprint

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Flavonoids, including fisetin, have been linked to a reduced risk of colorectal cancer (CRC) and have potential therapeutic applications for the condition. Fisetin, a natural flavonoid found in various fruits and vegetables, has shown promise in managing CRC due to its diverse biological activities. It has been found to influence key cell signaling pathways related to inflammation, angiogenesis, apoptosis, growth factors, and transcription factors. The results of this study demonstrate that fisetin induces colon cancer cell apoptosis through multiple mechanisms. It impacts the p53 pathway, leading to increased levels of p53 and decreased levels of MDM2, contributing to apoptosis induction. Fisetin also triggers the release of important components in the apoptotic process, such as Smac/DIABLO and cytochrome c. Furthermore, fisetin inhibits the COX2 and Wnt/EGFR/NF-ĸB signaling pathways, reducing Wnt target gene expression and hindering colony formation. It achieves this by regulating the activities of CDK2 and CDK4, reducing Rb phosphorylation, decreasing cyclin E levels, and increasing p21 levels, ultimately influencing E2F-1 and CDC2 protein levels. Additionally, fisetin has various effects on CRC cells, including inhibiting the phosphorylation of YB-1 and RSK, promoting the phosphorylation of ERK1/2, and disrupting the repair process of DSBs. Moreover, fisetin serves as an adjunct therapy for the prevention and treatment of PIK3CA-mutant CRC, resulting in a reduction of PI3K expression, AKT phosphorylation, mTOR activity, and downstream target proteins in CRC cells with a PIK3CA mutation. These findings highlight the multifaceted potential of fisetin in managing CRC and position it as a promising candidate for future therapy development.

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Different Roles of Apoptosis and Autophagy in the Development of Human Colorectal Cancer

Cited by 16 publications

References 114 publications

Identification of cuproptosis and ferroptosis-related subtypes and development of a prognostic signature in colon cancer

Identification of cuproptosis and ferroptosis-related subtypes and development of a prognostic signature in colon cancer

Caffeic acid phenethyl ester promotes oxaliplatin sensitization in colon cancer by inhibiting autophagy

A Narrative Review on Therapeutic Potential of Fisetin in Colorectal Cancer: Focusing on apoptosis and biochemical processes

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