Non-enzymatic glycoxidation linked with nutrition enhances the tumorigenic capacity of prostate cancer epithelia through AGE mediated activation of RAGE in cancer associated fibroblasts

Krisanits, Bradley A.; Woods, Pamela; Nogueira, Lourdes M.; Woolfork, Demarcus D.; Lloyd, Courtney E.; Baldwin, Andrew; Frye, Callan C.; Peterson, Kendell D.; Cosh, Sean; Guo, Qi-Jin; Spruill, Laura; Lilly, Michael B.; Helke, Kristi L.; Li, Hong; Hanna, George; Hamann, Mark; Thomas, Courtney; Ahmed, Mahtabuddin; Göõz, Monika; Findlay, Victoria J.; Turner, David P.

doi:10.1016/j.tranon.2022.101350

Cited by 12 publications

(15 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on the above proteomic analysis, ARE-RAGE signaling pathway might be associated with the antitumor activity of SW1990 after the combined use of G-6 and GEM. This pathway is regulated to increase ROS [ 18 , 19 ]. However, the accumulation of ROS is thought to be related to the disruption of MMP [ 24 ].…”

Section: Resultsmentioning

confidence: 99%

“…The receptor pathway is the main pathway of AGEs, and the most studied receptor is the receptor for advanced glycation endproducts (RAGE) [ 18 ]. RAGE is expressed in cancer cells, such as pancreatic cancer and prostate cancer, and is closely related to oxidative stress in the body [ 19 , 20 ]. The development of drug-resistant pancreatic cancer can be accelerated by RAGE-initiated signaling.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Nardoguaianone L Isolated from Nardostachys jatamansi Improved the Effect of Gemcitabine Chemotherapy via Regulating AGE Signaling Pathway in SW1990 Cells

Zheng

et al. 2022

Molecules

View full text Add to dashboard Cite

Pancreatic cancer is the seventh leading cause of cancer-related death worldwide and is known as “the king of cancers”. Currently, gemcitabine (GEM) as the clinical drug of choice for chemotherapy of advanced pancreatic cancer has poor drug sensitivity and ineffective chemotherapy. Nardoguaianone L (G-6) is a novel guaiane-type sesquiterpenoid isolated from Nardostachys jatamansi DC., and it exhibits anti-tumor activity. Based on the newly discovered G-6 with anti-pancreatic cancer activity in our laboratory, this paper aimed to evaluate the potential value of the combination of G-6 and GEM in SW1990 cells, including cell viability, cell apoptosis, colony assay and tandem mass tags (TMT) marker-based proteomic technology. These results showed that G-6 combined with GEM significantly inhibited cell viability, and the effect was more obvious than that with single drug. In addition, the use of TMT marker-based proteomic technology demonstrated that the AGE-RAGE signaling pathway was activated after medication-combination. Furthermore, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) assays were used to validate the proteomic results. Finally, apoptosis was detected by flow cytometry. In conclusion, G-6 combined with GEM induced an increase in ROS level and a decrease in MMP in SW1990 cells through the AGE-RAGE signaling pathway, ultimately leading to apoptosis. G-6 improved the effect of GEM chemotherapy and may be used as a potential combination therapy for pancreatic cancer.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nardoguaianone L Isolated from Nardostachys jatamansi Improved the Effect of Gemcitabine Chemotherapy via Regulating AGE Signaling Pathway in SW1990 Cells

Zheng

et al. 2022

Molecules

View full text Add to dashboard Cite

show abstract

“…Recently, it was shown that nitrosative stress and glycoxidation of proteins are increased in obese women compared to healthy controls as well as that bariatric surgery vastly normalizes detected abnormalities in these processes [35]. Interestingly, it has been shown that nutritionally related glycoxidation increases the tumorigenic potential of different cancer types [36,37] and glycoxidation has been recognized as a contributor to the vicious cycle in the development of lung cancer [38]. A tight inverse association was shown between the body fat percentage and antioxidant capacity [34] and decreased anti-oxidative defense, together with increased nitrosative stress, was found in patients with prostate and breast cancers [39].…”

Section: Metabolic Environment In Obesitymentioning

confidence: 99%

Oxidative Stress Linking Obesity and Cancer: Is Obesity a ‘Radical Trigger’ to Cancer?

Jovanović

Kovačević

Brkljačić

et al. 2023

IJMS

View full text Add to dashboard Cite

Obesity is on the rise worldwide, and consequently, obesity-related non-communicable diseases are as well. Nutritional overload induces metabolic adaptations in an attempt to restore the disturbed balance, and the byproducts of the mechanisms at hand include an increased generation of reactive species. Obesity-related oxidative stress causes damage to vulnerable systems and ultimately contributes to neoplastic transformation. Dysfunctional obese adipose tissue releases cytokines and induces changes in the cell microenvironment, promoting cell survival and progression of the transformed cancer cells. Other than the increased risk of cancer development, obese cancer patients experience higher mortality rates and reduced therapy efficiency as well. The fact that obesity is considered the second leading preventable cause of cancer prioritizes the research on the mechanisms connecting obesity to cancerogenesis and finding the solutions to break the link. Oxidative stress is integral at different stages of cancer development and advancement in obese patients. Hypocaloric, balanced nutrition, and structured physical activity are some tools for relieving this burden. However, the sensitivity of simultaneously treating cancer and obesity poses a challenge. Further research on the obesity–cancer liaison would offer new perspectives on prevention programs and treatment development.

show abstract

“…However, RAGE depletion in stromal cells arrested the AGE-driven cancer cell growth. This implies the role of AGEs-RAGE in the crosstalk between tumour cell and tumour-associated fibroblasts/stroma in eliciting cancer progression and metastasis, and the role of AGE-rich diet in inciting tumorigenic events via molecular interplay of tumour micro-milieu [ 39 ].…”

Section: Metabolic Imprint Of Ages In Cancersmentioning

confidence: 99%

AGEs and RAGE: metabolic and molecular signatures of the glycation-inflammation axis in malignant or metastatic cancers

Palanissami,

Paul

2023

Exploration of Targeted Anti-Tumor Therapy

View full text Add to dashboard Cite

From attributing mutations to cancers with the advent of cutting-edge genetic technology in recent decades, to re-searching the age-old theory of intrinsic metabolic shift of cancers (Warburg’s glycolysis), the quest for a precise panacea for mainly the metastatic cancers, remains incessant. This review delineates the advanced glycation end product (AGE)-receptor for AGE (RAGE) pathway driven intricate oncogenic cues, budding from the metabolic (glycolytic) reliance of tumour cells, branching into metastatic emergence of malignancies. Strong AGE-RAGE concomitance in metastasis, chemo-resistance and cancer resurgence adversely incite disease progression and patient mortality. At the conjunction of metabolic and metastatic shift of cancers, are the “glycolytically” generated AGEs and AGE-activated RAGE, instigating aberrant molecular pathways, culminating in aggressive malignancies. AGEs as by-products of metabolic insurgence, modify the metabolome, epigenome and microbiome, besides coercing the inter-, intra- and extra-cellular micro-milieu conducive for oncogenic events like epithelial-mesenchymal transition (EMT). AGE-RAGE synergistically elicit ATP surge for surplus energy, autophagy for apoptotic evasion and chemo-resistance, insulin-like growth factor 1 (IGF-1) for meta-inflammation and angiogenesis, high mobility group box-1 (HMGB1) for immune tolerance, S100 proteins for metastasis, and p53 protein attenuation for tumour suppression. AGEs are pronouncedly reported in invasive forms of breast, prostate, colon and pancreatic cancers, higher in patients with cancer than healthy counterparts, and higher in advanced stage than localized phase. Hence, the investigation of person-specific presence of AGEs, soluble RAGE and AGE-activated RAGE can be advocated as impending bio-markers for diagnostic, prognostic and therapeutic purposes, to predict cancer risk in patients with diabetes, obesity, metabolic syndrome as well as general population, to monitor prognosis and metastasis in patients with cancer, and to reckon complications in cancer survivors. Furthermore, clinical reports of exogenous (dietary) and endogenous (internally formed) AGEs in cancer patients, and contemporary clinical trials involving AGE-RAGE axis in cancer are underlined with theranostic implications.

show abstract

Non-enzymatic glycoxidation linked with nutrition enhances the tumorigenic capacity of prostate cancer epithelia through AGE mediated activation of RAGE in cancer associated fibroblasts

Cited by 12 publications

References 41 publications

Nardoguaianone L Isolated from Nardostachys jatamansi Improved the Effect of Gemcitabine Chemotherapy via Regulating AGE Signaling Pathway in SW1990 Cells

Nardoguaianone L Isolated from Nardostachys jatamansi Improved the Effect of Gemcitabine Chemotherapy via Regulating AGE Signaling Pathway in SW1990 Cells

Oxidative Stress Linking Obesity and Cancer: Is Obesity a ‘Radical Trigger’ to Cancer?

AGEs and RAGE: metabolic and molecular signatures of the glycation-inflammation axis in malignant or metastatic cancers

Contact Info

Product

Resources

About