Targeting PERK and GRP78 in Colorectal Cancer: Genetic Insights and Novel Therapeutic Approaches DOI Creative Commons
Sahar Mafi, Mehdi Dehghani, Bahman Khalvati

et al.

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 982, P. 176899 - 176899

Published: Aug. 15, 2024

Colorectal cancer (CRC) ranks among the leading causes of cancer-related deaths worldwide. Enhancing CRC diagnosis and prognosis requires development improved biomarkers therapeutic targets. Emerging evidence suggests that unfolded protein response (UPR) plays a pivotal role in progression, presenting new opportunities for diagnosis, treatment, prevention. This study hypothesizes genetic variants endoplasmic reticulum (ER) stress genes influence susceptibility. We examined frequencies SNPs PERK (rs13045) GRP78/BiP (rs430397) within South Iranian cohort. mapped cellular molecular features GRP78 colorectal cancer, observing their differential expressions tumor metastatic tissues. constructed co-expression protein-protein interaction networks performed gene set enrichment analysis, highlighting autophagy as significant pathway through KEGG. Furthermore, included 64 patients 60 control subjects. DNA extraction genotyping were conducted using high-resolution melting (HRM) analysis. Significant differences observed between tissues controls. Variations genotypes significantly correlated with risk. Utilizing Multi-Target Directed Ligands approach, dual PERK/GRP78 inhibitor was designed subjected to modeling studies. Docking experiments indicated high-affinity binding proposed both genes, GRP78, suggesting novel therapy CRC. These findings highlight importance understanding backgrounds different populations assess Polymorphisms UPR signaling elements may serve potential markers predicting susceptibility, paving way personalized strategies.

Language: Английский

Natural Compounds for Preventing Age-Related Diseases and Cancers DOI Open Access
Mi‐Ran Ki,

Sol Youn,

Dong Hyun Kim

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7530 - 7530

Published: July 9, 2024

Aging is a multifaceted process influenced by hereditary factors, lifestyle, and environmental elements. As time progresses, the human body experiences degenerative changes in major functions. The external internal signs of aging manifest various ways, including skin dryness, wrinkles, musculoskeletal disorders, cardiovascular diseases, diabetes, neurodegenerative cancer. Additionally, cancer, like aging, complex disease that arises from accumulation genetic epigenetic alterations. Circadian clock dysregulation has recently been identified as an important risk factor for cancer development. Natural compounds herbal medicines have gained significant attention their potential preventing age-related diseases inhibiting progression. These demonstrate antioxidant, anti-inflammatory, anti-proliferative, pro-apoptotic, anti-metastatic, anti-angiogenic effects well circadian regulation. This review explores cancers, specific natural targeting key features these conditions.

Language: Английский

Citations

9
Curcumin and its anti‐colorectal cancer potential: From mechanisms of action to autophagy DOI Creative Commons
Aranka Brockmueller, Vicenç Ruiz de Porras, Mehdi Shakibaei

et al.

Phytotherapy Research, Journal Year: 2024, Volume and Issue: 38(7), P. 3525 - 3551

Published: May 3, 2024

Abstract Colorectal cancer (CRC) development and progression, one of the most common cancers globally, is supported by specific mechanisms to escape cell death despite chemotherapy, including cellular autophagy. Autophagy an evolutionarily highly conserved degradation pathway involved in a variety processes, such as maintenance homeostasis clearance foreign bodies, its imbalance associated with many diseases. However, role autophagy CRC progression remains controversial, it has dual function, affecting either or survival, senescence tumor therapy. Indeed, numerous data have been presented that serves alternative apoptosis when latter ineffective apoptosis‐resistant cells, which why also referred programmed type II. Curcumin, active constituents Curcuma longa , great potential combat influencing various signaling pathways epigenetic regulation safe cost‐effective approach. This review discusses efficacy curcumin against vitro vivo, particularly modulation pathways. While clinical studies assessed prevention treatment, none specifically examined Nonetheless, we offer overview correlations support use this polyphenol prophylactic co‐therapeutic agent CRC.

Language: Английский

Citations

8
Regulatory function of endoplasmic reticulum stress in colorectal cancer: Mechanism, facts, and perspectives DOI
Zihan Liu, Qiong Liu,

Anqi Zeng

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 147, P. 114024 - 114024

Published: Jan. 6, 2025

Language: Английский

Citations

0
GRP78: A New Promising Candidate in Colorectal Cancer Pathogenesis and Therapy DOI
Song Wang, Neda Rahimian,

Aysa Hasanzade Bashkandi

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177308 - 177308

Published: Jan. 1, 2025

Language: Английский

Citations

0
Targeted modulation of dual-metal ion homeostasis to induce ER stress and cuproptosis for synergistic breast tumor suppression DOI

Xiaoxian Zhang,

Xuequan Zhang, Jiahui Zhu

et al.

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: unknown, P. 163248 - 163248

Published: April 1, 2025

Language: Английский

Citations

0
ATF family members as therapeutic targets in cancer: From mechanisms to pharmacological interventions DOI Creative Commons

Xueyao Zhang,

Zhijia Li, Xiaochun Zhang

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 208, P. 107355 - 107355

Published: Aug. 22, 2024

The activating transcription factor (ATF)/ cAMP-response element binding protein (CREB) family represents a large group of basic zone leucine zip (bZIP) factors (TFs) with variety physiological functions, such as endoplasmic reticulum (ER) stress, amino acid heat oxidative integrated stress response (ISR) and thus inducing cell survival or apoptosis. Interestingly, ATF has been increasingly implicated in autophagy ferroptosis recent years. Thus, the is important for homeostasis its dysregulation may promote disease progression including cancer. Current therapeutic approaches to modulate include direct modulators, upstream post-translational modifications (PTMs) modulators. This review summarizes structural domain PTMs feature ATF/CREB comprehensively explores molecular regulatory mechanisms. On this basis, their pathways affecting proliferation, metastasis, drug resistance various types cancer cells are sorted out discussed. We then systematically summarize status applications existing modulators finally look forward future prospect clinical treatment tumors by modulating family.

Language: Английский

Citations

2
Modulating Endoplasmic Reticulum Stress in Gastrointestinal Cancers: Insights from Traditional Chinese Medicine DOI Creative Commons

Qinyi Li,

Xiaohong Zhao, Huan Yang

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(12), P. 1599 - 1599

Published: Nov. 27, 2024

Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) play critical roles in tumorigenesis, cancer progression, drug resistance. Persistent activation of ER system enhances survival capacities malignant tumor cells, including increased proliferation, invasion, resistance to treatment. Dysregulation function resultant is a common cellular therapies may lead cell death. Currently, growing evidence suggests that Traditional Chinese medicine (TCM), either as monotherapy or combination with other treatments, offers significant advantages preventing cancer, inhibiting growth, reducing surgical complications, improving sensitivity, mitigating drug-induced damage. Some these natural products have even entered clinical trials primary complementary anticancer agents. In this review, we summarize effects TCM monomers/natural on gastrointestinal (GI) tumors explore their mechanisms through modulation. We believe ongoing laboratory research development TCM-based hold considerable potential for advancing future treatments.

Language: Английский

Citations

1
Targeting PERK and GRP78 in Colorectal Cancer: Genetic Insights and Novel Therapeutic Approaches DOI Creative Commons
Sahar Mafi, Mehdi Dehghani, Bahman Khalvati

et al.

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 982, P. 176899 - 176899

Published: Aug. 15, 2024

Colorectal cancer (CRC) ranks among the leading causes of cancer-related deaths worldwide. Enhancing CRC diagnosis and prognosis requires development improved biomarkers therapeutic targets. Emerging evidence suggests that unfolded protein response (UPR) plays a pivotal role in progression, presenting new opportunities for diagnosis, treatment, prevention. This study hypothesizes genetic variants endoplasmic reticulum (ER) stress genes influence susceptibility. We examined frequencies SNPs PERK (rs13045) GRP78/BiP (rs430397) within South Iranian cohort. mapped cellular molecular features GRP78 colorectal cancer, observing their differential expressions tumor metastatic tissues. constructed co-expression protein-protein interaction networks performed gene set enrichment analysis, highlighting autophagy as significant pathway through KEGG. Furthermore, included 64 patients 60 control subjects. DNA extraction genotyping were conducted using high-resolution melting (HRM) analysis. Significant differences observed between tissues controls. Variations genotypes significantly correlated with risk. Utilizing Multi-Target Directed Ligands approach, dual PERK/GRP78 inhibitor was designed subjected to modeling studies. Docking experiments indicated high-affinity binding proposed both genes, GRP78, suggesting novel therapy CRC. These findings highlight importance understanding backgrounds different populations assess Polymorphisms UPR signaling elements may serve potential markers predicting susceptibility, paving way personalized strategies.

Language: Английский

Citations

1