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

Liu, Zhihang; Peng, Shaoyong; Tang, Ge; Xu, Gaopo; Xie, Yumo; Shen, Dingcheng; Zhu, Mingxuan; Huang, Yaoyi; Wang, Xiaolin; Yu, Huichuan; Huang, Meijin; Luo, Yanxin

doi:10.1016/j.ebiom.2023.104496

Cited by 28 publications

(18 citation statements)

References 59 publications

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“…Notably, amino acids, bile acids, and fatty acids were the most common dysregulated metabolite biomarkers utilized to screen for CRC and precancerous lesions. However, the application of plasma metabolomics in mCRC is rarely reported [15][16][17]. Overall, this study reveals that plasma targeting metabolome may be an effective way to diagnose mCRC and potential therapeutic targets.…”

Section: Introductionmentioning

confidence: 91%

Plasma metabolism-related biomarkers enable non-invasive precision detection and individualized treatment in metastatic colorectal cancer

Shan

Zhao

Zhou

et al. 2023

Preprint

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Colorectal cancer (CRC) is one of the most deadly malignancies worldwide, especially metastatic CRC (mCRC), whose diagnosis and therapy are limited. Here, the targeted metabolomes of patients with CRC and mCRC were analyzed to explore new biomarkers and treatment strategies. First, plasma was collected from patients with CRC (n = 50) and mCRC (n = 50). Serum metabolites of amino acids, bile acids, and fatty acids were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Subsequently, 60 CRC and mCRC were randomly selected as the training set. A total of 27 amino acids, nine bile acids, and 16 amino acids were detected, among which 13 metabolites were significantly different. KEGG functional analysis showed that these differential metabolites play an essential role in the metabolism of fatty and bile acids. ROC analysis showed that CRC and mCRC could be well discriminated by 13 different metabolic indices, among which the sensitivity and specificity of the single index C18:2 were 0.833 and 0.800. To identify these markers, 40 CRC and mCRC patients were used as validation sets. The identification results of GCA, C17:0, and C18:2 were consistent with previous results. The AUC of GCA, C17:0, combined with C18:2, can reach 0.86, much higher than the traditional index CEA (0.70) and CA19.9 (0.80).Furthermore, Pearson analysis showed a significant correlation between GCA and CA19.9. Twenty-five mCRC patients were selected, and the AUC of GCA, CEA, and CA19.9 were 0.74, 0.74, and 0.70, respectively. In addition, the AUC of GCA and CEA combined with CA19.9 was significantly increased to 0.87. Taken together, our study showed that GCA, C17:0, in combination with C18:2, is superior to the clinical classic in differentiating CRC and mCRC. At the same time, GCA, in combination with CEA and CA19.9, can significantly improve the diagnosis of mCRC with liver metastases. This study is expected to provide new indicators for the diagnosis of mCRC and new strategies for the treatment of mCRC.

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Section: Introductionmentioning

confidence: 91%

Plasma metabolism-related biomarkers enable non-invasive precision detection and individualized treatment in metastatic colorectal cancer

Shan

Zhao

Zhou

et al. 2023

Preprint

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“…Several models have been proposed to use caloric restriction to enhance the effect of selected anticancer agents. In in-vivo and in-vitro models, colorectal cancer cells could be shown during caloric restriction to enter a slow-cycling state, while displaying activation of the ferroptosis pathway with increased levels of Fe 2+ and lipid radical oxygen species [22 ▪ ]. These quiescent cells were prone to develop drug tolerance and are suspected to be the precursors of later cancer relapse.…”

Section: Effects Of Caloric Restriction In Preclinical Cancer Modelsmentioning

confidence: 99%

“…These quiescent cells were prone to develop drug tolerance and are suspected to be the precursors of later cancer relapse. Combining caloric restriction with ferroptosis inducers was able to eliminate also these quiescent drug-resistant cells [22 ▪ ]. Nutrient-restricted media may imitate caloric restriction under in-vitro conditions and induce autophagy in tumor cells.…”

Section: Effects Of Caloric Restriction In Preclinical Cancer Modelsmentioning

confidence: 99%

Caloric restriction and fasting-mimicking diets in the treatment of cancer patients

Arends

2023

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Purpose of review Different forms of caloric restriction for patients with cancer are widely advertised in lay circles, based mainly on promising preclinical experiments, while evidence from clinical trials is still preliminary. This review aims to present physiological responses to fasting and update knowledge on recently accumulated evidence from preclinical models and clinical trials. Recent findings Like other mild stressors, caloric restriction induces hormetic changes in healthy cells, which increase the tolerance to subsequent more severe stressors. While protecting healthy tissues, caloric restriction sensitizes malignant cells to toxic interventions because of their deficiencies in hormetic mechanisms, especially control of autophagy. In addition, caloric restriction may activate anticancer-directed immune cells and deactivate suppressive cells, thus increasing immunosurveillance and anticancer cytotoxicity. These effects may combine to increase the effectivity of cancer treatments while limiting adverse events. Though evidence obtained from preclinical models is promising, clinical trials in cancer patients so far have been preliminary. In clinical trials it will remain essential to avoid inducing or aggravating malnutrition. Summary Based on physiology and evidence from preclinical models, caloric restriction is a promising candidate as a potential combination partner for clinical anticancer treatment. However, large randomized clinical trials investigating effects on clinical outcome in patients with cancer are still lacking.

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“…Switches cancer cells from an active proliferative to a slow-cycling state; increases mRNA expression of proapoptotic genes and decreases mRNA expression of antiapoptotic genes [36][37][38] ; enhances GLUT expression and improves cell survival under low-glucose conditions [39] It is difficult for most people to stick with fasting for an extended period…”

Section: Role In Crc Mechanism(s) Underlying the Effects On Crc Limit...mentioning

confidence: 99%

Mechanistic associations between dietary patterns and colorectal cancer

Han,

Liu,

et al. 2023

J Nutr Oncol

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Colorectal cancer (CRC) is a common cancer with high morbidity and mortality rates. Its occurrence and development are determined by many factors, including genetics, the environment, lifestyle, and so on. The occurrence of CRC is often accompanied by changes in the intestinal microenvironment. Numerous studies have focused on the association between dietary patterns, dietary components, and CRC now. This article reviews five different dietary patterns: the Western diet, the Mediterranean diet, the ketogenic diet, the Dietary Approaches to Stop Hypertension diet, and fasting, and the mechanistic associations between their food components and CRC. The finding can provide a reference for further studies on the association between different dietary patterns and CRC and will help clinicians formulate reasonable and feasible dietary interventions.

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

Cited by 28 publications

References 59 publications

Plasma metabolism-related biomarkers enable non-invasive precision detection and individualized treatment in metastatic colorectal cancer

Plasma metabolism-related biomarkers enable non-invasive precision detection and individualized treatment in metastatic colorectal cancer

Caloric restriction and fasting-mimicking diets in the treatment of cancer patients

Mechanistic associations between dietary patterns and colorectal cancer

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