Bodywide ecological interventions on cancer

Nature Medicine, Год журнала: 2023, Номер 29(1), С. 59 - 74

Опубликована: Янв. 1, 2023

Язык: Английский

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The Warburg Effect Explained: Integration of Enhanced Glycolysis with Heterogeneous Mitochondria to Promote Cancer Cell Proliferation

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(21), С. 15787 - 15787

Опубликована: Окт. 31, 2023

The Warburg effect is the long-standing riddle of cancer biology. How does aerobic glycolysis, inefficient in producing ATP, confer a growth advantage to cells? A new evaluation large set literature findings covering and its yeast counterpart, Crabtree effect, led an innovative working hypothesis presented here. It holds that enhanced glycolysis partially inactivates oxidative phosphorylation induce functional rewiring TCA cycle enzymes generate non-canonical metabolic pathways sustain faster rates. has been structured by constructing two maps, one for metabolism other effect. New lines investigation, suggested these are discussed as instrumental leading toward better understanding biology order allow development more efficient metabolism-targeted anticancer drugs.

Язык: Английский

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Health Benefits of Coffee Consumption for Cancer and Other Diseases and Mechanisms of Action

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2706 - 2706

Опубликована: Янв. 31, 2023

Coffee is one of the most widely consumed beverages worldwide, and epidemiology studies associate higher coffee consumption with decreased rates mortality neurological metabolic diseases, including Parkinson's disease type 2 diabetes. In addition, there also evidence that associated lower colon rectal cancer, as well breast, endometrial, other cancers, although for some these results are conflicting. These reflect chemopreventive effects coffee; may be therapeutic forms breast this needs to further investigated. The mechanisms or chemotherapeutic over 1000 individual compounds in roasted complex vary different diseases. Some related nuclear factor erythroid (Nrf2)-regulated pathways target oxidative stress induce reactive oxygen species kill diseased cells (primarily therapeutic). There involvement receptors which include aryl hydrocarbon receptor (AhR) orphan 4A1 (NR4A1), contributions from epigenetic gut microbiome. Further elucidation will facilitate potential future clinical applications extracts treating cancer inflammatory

Язык: Английский

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Fasting-mimicking diet synergizes with ferroptosis against quiescent, chemotherapy-resistant cells

EBioMedicine, Год журнала: 2023, Номер 90, С. 104496 - 104496

Опубликована: Фев. 28, 2023

More than ten randomized clinical trials are being tested to evaluate the efficacy, effectiveness and safety of a fasting-mimicking diet (FMD) combined with different antitumor agents.UMI-mRNA sequencing, Cell-cycle analysis, Label retention, metabolomics, Multilabeling et al. were used explore mechanisms. A tandem mRFP-GFP-tagged LC3B, Annexin-V-FITC Apoptosis, TUNEL, H&E, Ki-67 animal model was search for synergistic drugs.Here we showed that fasting or FMD retards tumor growth more effectively but does not increase 5-fluorouracil/oxaliplatin (5-FU/OXA) sensitivity apoptosis in vitro vivo. Mechanistically, demonstrated CRC cells would switch from an active proliferative slow-cycling state during fasting. Furthermore, metabolomics shows cell proliferation decreased survive nutrient stress vivo, as evidenced by low level adenosine deoxyadenosine monophosphate. decrease achieve increased survival relapse after chemotherapy. In addition, these fasting-induced quiescent prone develop drug-tolerant persister (DTP) postulated be responsible cancer metastasis. Then, UMI-mRNA sequencing uncovered ferroptosis pathway most influenced Combining inducer treatment leads inhibition eradication boosting autophagy.Our results suggest could improve activity + chemotherapy highlight potential therapeutic opportunity avoid DTP cells-driven therapy failure.A full list funding bodies can found Acknowledgements section.

Язык: Английский

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Glycine homeostasis requires reverse SHMT flux

Cell Metabolism, Год журнала: 2024, Номер 36(1), С. 103 - 115.e4

Опубликована: Янв. 1, 2024

Язык: Английский

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Ketogenic diet alters the epigenetic and immune landscape of prostate cancer to overcome resistance to immune checkpoint blockade therapy

Cancer Research, Год журнала: 2024, Номер 84(10), С. 1597 - 1612

Опубликована: Апрель 8, 2024

Resistance to immune checkpoint blockade (ICB) therapy represents a formidable clinical challenge limiting the efficacy of immunotherapy. In particular, prostate cancer poses for ICB due its immunosuppressive features. A ketogenic diet (KD) has been reported enhance response in some other models. However, adverse effects associated with continuous KD were also observed, demanding better mechanistic understanding and optimized regimens using as an immunotherapy sensitizer. this study, we established series ICB-resistant cell lines developed highly effective strategy combining anti-PD1 anti-CTLA4 antibodies histone deacetylase inhibitor (HDACi) vorinostat, cyclic (CKD), or dietary supplementation ketone body β-hydroxybutyrate (BHB), which is endogenous HDACi. CKD BHB each delayed tumor growth monotherapy, both adaptive immunity required antitumor activity CKD. Single-cell transcriptomic proteomic profiling revealed that HDACi ketogenesis enhanced through cell-intrinsic mechanisms, including upregulation MHC class I molecules, -extrinsic such CD8+ T-cell chemoattraction, M1/M2 macrophage rebalancing, monocyte differentiation toward antigen-presenting cells, diminished neutrophil infiltration. Overall, these findings illuminate potential path cancer.

Язык: Английский

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The Hallmarks of Precancer

Cancer Discovery, Год журнала: 2024, Номер 14(4), С. 683 - 689

Опубликована: Апрель 4, 2024

Summary: Research on precancers, as defined at-risk tissues and early lesions, is of high significance given the effectiveness intervention. We discuss need for risk stratification to prevent overtreatment, an emphasis role genetic epigenetic aging when considering risk, importance integrating macroenvironmental factors with molecules cells in lesions normal developing effective intervention health policy strategies.

Язык: Английский

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Tumor metabolic regulators: key drivers of metabolic reprogramming and the promising targets in cancer therapy

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Янв. 9, 2025

Metabolic reprogramming within the tumor microenvironment (TME) is a hallmark of cancer and crucial determinant progression. Research indicates that various metabolic regulators form network in TME interact with immune cells, coordinating response. dysregulation creates an immunosuppressive TME, impairing antitumor In this review, we discuss how affect cell crosstalk TME. We also summarize recent clinical trials involving challenges metabolism-based therapies translation. word, our review distills key regulatory factors their mechanisms action from complex metabolism, identified as regulators. These provide theoretical basis research direction for development new strategies targets therapy based on reprogramming. Refining Depicting between stromal cells during Emphasizing unresolved translation advantages personalized treatment. Providing support therapies.

Язык: Английский

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Intermittent fasting and time-restricted eating role in dietary interventions and precision nutrition

Frontiers in Public Health, Год журнала: 2022, Номер 10

Опубликована: Окт. 28, 2022

Intermittent fasting (IF), time-restricted eating (TRE) and fasting-mimicking diets (FMD) are gaining popularity as weight loss programs. As such, the timing frequency of meals have been recognized essential contributors to improving cardiometabolic health a role adjuvant therapy in cancer. Randomized controlled trials suggested that associated with IF is due reduced energy intake time restriction. Although supervised TRE clinical documented dietary caloric intake, many free-living studies focused on without complete characterization density, or macronutrient composition. It possible both caloric-restriction time-restriction protocols could work synergistically additively improve metabolic outcomes. Like personalized medicine, achieving precision nutrition mandates provision right nutrients patient at time. To accomplish this goal, future need evaluate benefits TRE. were conducted different populations, ethnic groups, ages, geographic distribution, physical activity levels, body composition patients obesity, diabetes, cardiovascular diseases. Also, it crucial analyze density related circadian rhythm meals. conceivable may contribute strategies achieve optimal health. However, more research needed effects outcomes any side effects.

Язык: Английский

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Metabolism of Selenium, Selenocysteine, and Selenoproteins in Ferroptosis in Solid Tumor Cancers

Biomolecules, Год журнала: 2022, Номер 12(11), С. 1581 - 1581

Опубликована: Окт. 28, 2022

A potential target of precision nutrition in cancer therapeutics is the micronutrient selenium (Se). Se metabolized and incorporated as amino acid selenocysteine (Sec) into 25 human selenoproteins, including glutathione peroxidases (GPXs) thioredoxin reductases (TXNRDs), among others. Both processes Sec metabolism for production selenoproteins action are utilized by cells from solid tumors a protective mechanism against oxidative damage to resist ferroptosis, an iron-dependent cell death mechanism. Protection ferroptosis requires sustained selenoprotein GPX4, which involves increasing uptake Se, potentially activating metabolic pathways such trans-selenation pathway TXNRD1-dependent decomposition inorganic selenocompounds sustain GPX4 synthesis. Additionally, endoplasmic reticulum-resident also affect apoptotic responses presence selenocompounds. Selenoproteins may help adapting increased challenges modified nutrient that result Warburg switch. Finally, rewire hierarchy use Se-related machinery prioritize essential adaptations damage. In this review, we discuss both evidence gaps knowledge on how Sec, promote their survival particularly via resistance ferroptosis.

Язык: Английский

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