Determination of Rutin's antitumoral effect on EAC solid tumor by AgNOR count and PI3K/AKT/mTOR signaling pathway

Yılmaz, Seher; Doğanyiğit, Züleyha; Okan, Aslı; Ateş, Şükrü; Söylemez, Evrim Suna Arıkan; Nisari, Mehtap; Farooqı, Ammad Ahmad

doi:10.1007/s12032-023-01999-7

Cited by 5 publications

(3 citation statements)

References 55 publications

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“…However, it has been reported that melatonin induces apoptosis of cancer cells by suppressing PI3K, Akt and mTOR signaling pathways [33]. Yilmaz et al reported in their study that the antioxidant rutin, which they administered at different doses, decreased the tumor volume by suppressing the mTOR signaling pathway [34].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Ehrlich ascites carcinoma growth by melatonin: Studies with micro-CT

YILMAZ,

DOĞANYIĞIT,

OCAK

et al. 2024

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Melatonin is a versatile indolamine synthesized and secreted by the pineal gland in response to the photoperiodic information received by the retinohypothalamic signaling pathway. Melatonin has many benefits, such as organizing circadian rhythms and acting as a powerful hormone. We aimed to show the antitumor effects of melatonin in both in vivo and in vitro models through the mammalian target of rapamycin (mTOR) signaling pathway and the Argyrophilic Nucleolar Regulatory Region (AgNOR), using the Microcomputed Tomography (Micro CT). Ehrlich ascites carcinoma (EAC) cells were administered into the mice by subcutaneous injection.Animals with solid tumors were injected intraperitoneally with 50 and 100 mg/kg melatonin for 14 days. Volumetric measurements for the taken tumors were made with micro-CT imaging, immunohistochemistry (IHC), real-time polymerase chain reaction (PCR) and AgNOR. Statistically, the tumor tissue volume in the Tumor+100 mg/kg melatonin group was significantly lower than that in the other groups in the data obtained from micro-CT images. In the IHC analysis, the groups treated with Tumor+100 mg/kg melatonin were compared when the mTOR signaling pathway and factor 8 (F8) expression were compared with the control group. It was determined that there was a significant decrease (p < 0.05). Significant differences were found in the total AgNOR area/nuclear area (TAA/NA) ratio in the treatment groups (p < 0.05). Furthermore, there were significant differences between the amount of mTOR mRNA for the phosphatidylinositol 3-kinase (PI3K), AKT Serine/Threonine Kinase (PKB/AKT) genes (p < 0.05). Cell apoptosis was evaluated with Annexin V in an in vitro study with different doses of melatonin; It was observed that 100 µg/mL melatonin dose caused an increase in the apoptotic cell death. In this study, we have reported anti-tumor effects of melatonin in cell culture studies as well as in mice models. Comprehensive characterization of the melatonin-mediated cancer inhibitory effects will be valuable in advancing our fundamental molecular understanding and translatability of pre-clinical findings to earlier phases of clinical trials.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Ehrlich ascites carcinoma growth by melatonin: Studies with micro-CT

YILMAZ,

DOĞANYIĞIT,

OCAK

et al. 2024

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“…Wealth of information has greatly advanced our current conceptual understanding of the mechanistic basis for the involvement of phosphatidylinositol-3-kinases in diseases and assesses the preclinical and clinical breakthroughs related to phosphatidylinositol-3-kinases inhibitors (74)(75)(76)(77)(78)(79)(80). The state of the art in the regulation of PI3K/AKT signaling by circRNAs is discussed.…”

Section: Regulation Of Pi3k/akt/mtor Pathwaymentioning

confidence: 99%

Regulatory role of circular RNAs in oral squamous cell carcinoma

Attar,

Noel,

Romero

et al. 2023

Cell Mol Biol (Noisy-le-grand)

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OSCC is a genomically complicated disease and advancements in the modern era of molecular oncology have enabled researchers to portray near-to-complete resolution of signaling landscape. Over the last two decades, overwhelming proof-of-concept has established mechanistic regulatory role of non-coding RNAs in carcinogenesis, including OSCC. Circular RNAs demonstrate a burgeoning facet of oncology research and molecular biologists are only beginning to appreciate and recognize the significance of circRNAs in the pathogenesis of OSCC. Regulatory roles of non-coding RNAs in the re-shaping of signaling pathways offer plausible strategies for prevention/inhibition of OSCC. Circular RNAs have mechanistic roles in OSCC and "sponge effects" mediated by a wider variety of circRNAs need to be rationally targeted for effective cancer prevention. Phenomenal and cutting-edge research works in different types of animal models will further refine our knowledge for selection of most promising circRNAs as pharmacologically valuable targets.

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“…The PI3K/AKT/mTOR signaling pathway is also integral in the study of small molecule compounds. In a recent study, rutin, a flavonoid found in fruits and vegetables, demonstrated antitumor effects both in vivo and in vitro at different doses by modulating the mTOR signaling pathway [ 18 ]. In CRC, frequent mutations in both the PI3K pathway and the mitogen-activated protein kinase (MAPK) pathway promote tumor progression often alongside other common mutations in the wingless-type MMTV integration site family (WNT) signaling pathway, p53 and transforming growth factor beta (TGFβ) signaling pathways [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Leukotriene B4 receptor knockdown affects PI3K/AKT/mTOR signaling and apoptotic responses in colorectal cancer

Tang,

Wang,

Zhao

et al. 2024

Biomol Biomed

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Colorectal cancer (CRC) presents a landscape of intricate molecular dynamics. In this study, we focused on the role of the leukotriene B4 receptor (LTB4R) in CRC, exploring its significance in the disease's progression and potential therapeutic approaches. Using bioinformatics analysis of the GSE164191 and the Cancer Genome Atlas-colorectal adenocarcinoma (TCGA-COAD) datasets, we identified LTB4R as a hub gene influencing CRC prognosis. Subsequently, we examined the relationship between LTB4R expression, apoptosis, and the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway through cellular and mice experiments. Our findings revealed that LTB4R is highly expressed in CRC samples and is pivotal for determining prognosis. In vitro experiments demonstrated that silencing LTB4R significantly impeded CRC cell viability, migration, invasion, and colony formation. Correspondingly, in vivo tests indicated that LTB4R knockdown led to markedly slower tumor growth in mice models. Further in-depth investigation revealed that LTB4R knockdown significantly amplified the apoptosis in CRC cells and upregulated the expression of apoptosis-related proteins, such as caspase-3 and caspase-9, while diminishing p53 expression. Interestingly, silencing LTB4R also resulted in a significant downregulation of the PI3K/AKT/mTOR signaling pathway. Moreover, pretreatment with the PI3K activator 740Y-P only partially attenuated the effects of LTB4R knockdown on CRC cell behavior, emphasizing LTB4R's dominant influence in CRC cell dynamics and signaling pathways. LTB4R stands out as a critical factor in CRC progression, profoundly affecting cellular behavior, apoptotic responses, and the PI3K/AKT/mTOR signaling pathway. These findings not only shed light on LTB4R's role in CRC but also establish it as a potential diagnostic biomarker and a promising target for therapeutic intervention.

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Determination of Rutin's antitumoral effect on EAC solid tumor by AgNOR count and PI3K/AKT/mTOR signaling pathway

Cited by 5 publications

References 55 publications

Inhibition of Ehrlich ascites carcinoma growth by melatonin: Studies with micro-CT

Inhibition of Ehrlich ascites carcinoma growth by melatonin: Studies with micro-CT

Regulatory role of circular RNAs in oral squamous cell carcinoma

Leukotriene B4 receptor knockdown affects PI3K/AKT/mTOR signaling and apoptotic responses in colorectal cancer

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