Molecular mechanisms of action of Trehalose in cancer: A comprehensive review

Chaitanya, Nyshadham S.N.; Devi, Arpita; Sahu, Sibani; Alugoju, Phaniendra

doi:10.1016/j.lfs.2020.118968

Cited by 22 publications

(17 citation statements)

References 93 publications

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“…Based on the content data of the constituents and the findings, we inferred that phenols, flavonoids, and oligosaccharides were probably the main compounds that exhibited the hypoglycemic and antioxidant activities ( 27 , 28 ). Among the above 36 phytochemicals, in particular, the α,α-trehalose in PMEAT, a natural non-reducing disaccharide, has been reported to possess a pleiotropic role in various physiological conditions such as oxidative stress protection, inflammation prevention, and inhibition of protein denaturation and neurodegeneration ( 29 ). According to the quantitative analysis, its content proportion in PMEAT was not <13%.…”

Section: Resultsmentioning

confidence: 99%

“…It was probably due to α, α-trehalose, and procyanidin A2 identified in the PMEAT led to the in vitro antioxidant activity. As explicated in a review article by Chaitanya et al (29), trehalose possessed an antioxidant activity by targeting cell progression, angiogenesis, and metastasis pathways at the molecular level. In addition, Wang et al (56) reported that procyanidin A2 protected cells against the damage from inflammation and oxidative injury by targeting NF-kB, MAPK, and Nrf2 pathways in RAW264.7 cells.…”

Section: Antioxidant Activity Of Pmeat In Vitromentioning

confidence: 99%

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Characterization, Hypoglycemic Activity, and Antioxidant Activity of Methanol Extracts From Amomum tsao-ko: in vitro and in vivo Studies

Xie

et al. 2022

Front. Nutr.

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The dried fruit of Amomum tsao-ko is well-known as a spice as well as a Chinese traditional herb. This study aimed to identify the bioactive constituents in the powder of methanol extract from Amomum tsao-ko (PMEAT) and to evaluate the hypoglycemic and antioxidant effects of PMEAT, in vitro and in vivo. We identified 36 phytochemicals in PMEAT by employing HPLC-MS/MS. PMEAT solution was found to have potent α-glucosidase-inhibiting activity (IC50, 0.145 mg/mL) in vitro, twice as strong as that of acarbose (IC50, 0.273 mg/mL). To investigate the hypoglycemic activity of PMEAT in vivo, we studied the impact of low-dose PMEAT (the addition of 100 mg/kg PMEAT to the mice diet) and high-dose PMEAT (200 mg/kg PMEAT addition) treatments in STZ-induced diabetic mice. After 6 weeks of intervention, significantly decreased fasting blood glucose (FBG) (p < 0.05), significantly decreased area under the curve (AUC) of the oral glucose tolerance test (p < 0.05), significantly decreased HOMA-IR (p < 0.05), and significantly increased HOMA-β (p < 0.05) were observed in the high-dose PMEAT group. Moreover, we performed an antioxidant activity experiment in vitro. The results showed that PMEAT had a strong ability to scavenge DPPH (IC50, 0.044 mg/mL) as well as ABTS free radicals (IC50, 0.040 mg/mL). In an animal experiment conducted on oxidative damage mice model which was induced by D-glucose and a high-fat diet, we observed significantly increased dismutase (SOD) (p < 0.01), glutathione (GSH) (p < 0.01), and glutathione peroxidase (GSH-Px) (p < 0.01) and significantly reduced malondialdehyde (MDA) and 8-ISO-prostaglandin-PGF2α (8-ISO-PGF2α), after treatment with PMEAT for 90 days. In conclusion, this study reveals the therapeutic potential of Amomum tsao-ko for the treatment of diabetes and helps us discover new antioxidant candidates from natural sources.

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Section: Resultsmentioning

confidence: 99%

Section: Antioxidant Activity Of Pmeat In Vitromentioning

confidence: 99%

Characterization, Hypoglycemic Activity, and Antioxidant Activity of Methanol Extracts From Amomum tsao-ko: in vitro and in vivo Studies

Xie

et al. 2022

Front. Nutr.

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“…Alongside macropinocytosis, never hitherto described in trehalose-treated cells, this compound was also expected to stimulate macroautophagy (commonly referred to as autophagy) in U373-MG and T98G glioblastoma cells, as documented by us and others in a variety of normal and tumor cells [5,6,12]. Microtubule-associated protein 1 A/1B-light chain 3 (LC3) is the most widely used molecular marker of autophagosome biogenesis [13].…”

Section: Trehalose Induced Autophagy In U373-mg and T98g Cells To A D...mentioning

confidence: 88%

“…From this perspective, trehalose (a disaccharide of glucose monomers joined by a (1→1) glycosidic bond) [20] is attracting the attention of researchers due to its pleiotropic, protective role in a variety of pathophysiological conditions, as recently highlighted [21]. In cancer cell biology, under different experimental and cellular contexts, trehalose and its derivatives have been demonstrated to target various cell processes, including increased apoptosis, and decreased cell proliferation, migration and metastasis [5].…”

Section: Discussionmentioning

confidence: 99%

“…Listed "generally recognized as safe" (GRAS) by the Food and Drug Administration in 2000, it is also commonly used as a supplement in the food industry. Initially used as a cryoprotectant for tissues and cells, over the last 15 years trehalose has attracted attention for its therapeutic potential in a variety of neurodegenerative diseases [4] and cancer [5].…”

Section: Introductionmentioning

confidence: 99%

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The autophagy inducer trehalose stimulates macropinocytosis in NF1-deficient glioblastoma cells

et al. 2022

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Background Glioblastoma is a highly aggressive brain tumor. A big effort is required to find novel molecules which can cross the blood–brain barrier and efficiently kill these tumor cells. In this perspective, trehalose (α-glucopyranosyl‐[1→1]‐α‐d‐glucopyranoside), found in various dietary sources and used as a safe nutrient supplement, attracted our attention for its pleiotropic effects against tumor cells. Methods Human glioblastoma cell lines U373-MG and T98G were exposed to trehalose and analyzed at different time points. Cell proliferation was evaluated at medium term, and clonogenic capacity and cell morphology were evaluated at long term. Western blot was used to evaluate biochemical markers of autophagy (also measured in cells co-treated with EIPA or chloroquine), and mTOR, AMPK and ERK 1/2 signalling. Macropinocytosis was evaluated morphologically by bright-field microscopy; in cells loaded with the fluorescein-conjugated fluid-phase tracer dextran, macropinocytic vacuoles were also visualized by fluorescence microscopy, and the extent of macropinocytosis was quantified by flow cytometry. Results The long-term effect of trehalose on U373-MG and T98G cell lines was impressive, as indicated by a dramatic reduction in clonogenic efficiency. Mechanistically, trehalose proved to be an efficient autophagy inducer in macropinocytosis-deficient T98G cells and an efficient inducer of macropinocytosis and eventual cell death by methuosis in U373-MG glioblastoma cells, proved to be poorly responsive to induction of autophagy. These two processes appeared to act in a mutually exclusive manner; indeed, co-treatment of U373-MG cells with the macropinocytosis inhibitor, EIPA, significantly increased the autophagic response. mTOR activation and AMPK inhibition occurred in a similar way in the two trehalose-treated cell lines. Interestingly, ERK 1/2 was activated only in macropinocytosis-proficient U373-MG cells harbouring loss-of-function mutations in the negative RAS regulator, NF1, suggesting a key role of RAS signalling. Conclusions Our results indicate that trehalose is worthy of further study as a candidate molecule for glioblastoma therapy, due to its capacity to induce a sustained autophagic response, ultimately leading to loss of clonogenic potential, and more interestingly, to force macropinocytosis, eventually leading to cell death by methuosis, particularly in tumor cells with RAS hyperactivity. As a further anticancer strategy, stimulation of macropinocytosis may be exploited to increase intracellular delivery of anticancer drugs.

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Environmental insults and compensative responses: when microbiome meets cancer

Nagpal

Mande

2023

Discov Onc

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Tumor microenvironment has recently been ascribed a new hallmark—the polymorphic microbiome. Accumulating evidence regarding the tissue specific territories of tumor-microbiome have opened new and interesting avenues. A pertinent question is regarding the functional consequence of the interface between host-microbiome and cancer. Given microbial communities have predominantly been explored through an ecological perspective, it is important that the foundational aspects of ecological stress and the fight to ‘survive and thrive’ are accounted for tumor-micro(b)environment as well. Building on existing evidence and classical microbial ecology, here we attempt to characterize the ecological stresses and the compensative responses of the microorganisms inside the tumor microenvironment. What insults would microbes experience inside the cancer jungle? How would they respond to these insults? How the interplay of stress and microbial quest for survival would influence the fate of tumor? This work asks these questions and tries to describe this underdiscussed ecological interface of the tumor and its microbiota. It is hoped that a larger scientific thought on the importance of microbial competition sensing vis-à-vis tumor-microenvironment would be stimulated.

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Molecular mechanisms of action of Trehalose in cancer: A comprehensive review

Cited by 22 publications

References 93 publications

Characterization, Hypoglycemic Activity, and Antioxidant Activity of Methanol Extracts From Amomum tsao-ko: in vitro and in vivo Studies

Characterization, Hypoglycemic Activity, and Antioxidant Activity of Methanol Extracts From Amomum tsao-ko: in vitro and in vivo Studies

The autophagy inducer trehalose stimulates macropinocytosis in NF1-deficient glioblastoma cells

Environmental insults and compensative responses: when microbiome meets cancer

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