Dataset Information

Natural flavonoids exhibit potent anticancer activity by targeting microRNAs in cancer: A signature step hinting towards clinical perfection.

ABSTRACT: Cancer prevalence and its rate of incidence are constantly rising since the past few decades. Owing to the toxicity of present-day antineoplastic drugs, it is imperative to explore safer and more effective molecules to combat and/or prevent this dreaded disease. Flavonoids, a class of polyphenols, have exhibited multifaceted implications against several diseases including cancer, without showing significant toxicity towards the normal cells. Shredded pieces of evidence suggest that flavonoids can enhance drug sensitivity and suppress proliferation, metastasis, and angiogenesis of cancer cells by modulating several oncogenic or oncosuppressor microRNAs (miRNAs, miRs). They play pivotal roles in regulation of various biological and pathological processes, including various cancers. In the present review, the structure, chemistry and miR targeting efficacy of quercetin, luteolin, silibinin, genistein, epigallocatechin gallate, and cyanidin against several cancer types are comprehensively discussed. miRs are considered as next-generation medicine of recent times, and their targeting by naturally occurring flavonoids in cancer cells could be deemed as a signature step. We anticipate that our compilations related to miRNA-mediated regulation of cancer cells by flavonoids might catapult the clinical investigations and affirmation in the future.

SUBMITTER: Tuli HS

PROVIDER: S-EPMC9727168 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Natural flavonoids exhibit potent anticancer activity by targeting microRNAs in cancer: A signature step hinting towards clinical perfection.

Tuli Hardeep Singh HS Garg Vivek Kumar VK Bhushan Sakshi S Uttam Vivek V Sharma Uttam U Jain Aklank A Sak Katrin K Yadav Vikas V Lorenzo Jose M JM Dhama Kuldeep K Behl Tapan T Sethi Gautam G

Translational oncology 20221205

Cancer prevalence and its rate of incidence are constantly rising since the past few decades. Owing to the toxicity of present-day antineoplastic drugs, it is imperative to explore safer and more effective molecules to combat and/or prevent this dreaded disease. Flavonoids, a class of polyphenols, have exhibited multifaceted implications against several diseases including cancer, without showing significant toxicity towards the normal cells. Shredded pieces of evidence suggest that flavonoids ca ...[more]

PMID: 36473401

Similar Datasets

Project description:IntroductionCancer is a big challenge of the 21 century, whose defeat requires efficient antitumor drugs.ObjectivesThe paper aims to investigate the synergistic effect of two structural building blocks, phenothiazine and poly(ethylene glycol), towards efficient antitumor drugs.MethodsTwo PEGylated phenothiazine derivatives were synthetized by attaching poly(ethylene glycol) of 550 Da to the nitrogen atom of phenothiazine by ether or ester linkage. Their antitumor activity has been investigated on five human tumour lines and a mouse tumor line as well, by determination of IC50. The in vivo toxicity was determined by measuring the LD50 in BALB/c mice by the sequential method and the in vivo antitumor potential was measured by the tumours growth test. The antitumor mechanism was investigated by complexation studies of zinc and magnesium ions characteristic to the farnesyltransferase enzyme, by studies of self-aggregation in the cells proximity and by investigation of the antitumor properties of the acid species resulted by enzymatic cleavage of the PEGylated derivatives.ResultsThe two compounds showed antitumor activity, with IC50 against mouse colon carcinoma cell line comparable with that of the traditional antitumor drugs 5-Fluorouracil and doxorubicin. The phenothiazine PEGylation resulted in a significant toxicity diminishing, the LD50 in BALB/c mice increasing from 952.38 up to 1450 mg/kg, in phenothiazine equivalents. Both compounds inflicted a 92% inhibition of the tumour growth for doses much smaller than LD50. The investigation of the possible tumour inhibition mechanism suggested the nanoaggregate formation and the cleavage of ester bonds as key factors for the inhibition of cancer cell proliferation and biocompatibility improvement.ConclusionPhenothiazine and PEG building blocks have a synergetic effect working for both tumour growth inhibition and biocompatibility improvement. All these findings recommend the PEGylated phenothiazine derivatives as a valuable workbench for a next generation of antitumor drugs.

Project description:Radiation-induced pulmonary fibrosis (RIPF) is the most common bottleneck of radiation therapy (RT) that limits its tumor-killing effect. Up to date, there is no effective therapeutic agent for RIPF treatment due to absence of realistic preclinical models. Lungs of mice exposed to focal, highly localized dose of 75Gy-100Gy represents short time-taking (up to 6 weeks) modality for mimicking recent advanced RT, stereotactic body RT-associated lung fibrosis. However, extensive fibrosis and possibility of animal lethality resulted from exposure to high dose raises a question regarding the appropriate dose threshold for limiting unnecessary responses and obtain clinically relevant results. We observed in preliminary trials that lung tissues of 65Gy-exposed mice are still able to develop inflammation and fibrosis at the same time cap. But the molecular changes associated with dose reduction is still unknown. To examine this, bulk RNA from 65Gy and 75Gy irradiated as well as normal lung tissues of mice were obtained, and analysed using computational approach to uncover the transcriptomal similarities and differences between the differentially irradiated samples. Differentially expressed genes (DEGs) were analysed and 2-week and 6-week intersected DEGs as well as 65 and 75Gy exclusive DEGs at 2-week and 6-week time points were detected using venn diagramme. Expression direction of intersected DEGs between 65Gy and 75Gy was checked and found to be consistent at both inflammation and fibrosis stages proven visually by MDS and heatmap graphs. All-times intersected DEGs are 488 and involved in inflammation, cytokine production, and cell proliferation; 2-week intersected DEGs are 221 and involved in cell cycle and DNA damage; 6-week intersected DEGs are 403 and involved in immunoglobin production, extracellular matrix (ECM) deposition, and ECM-receptor interactions. Interestingly, only 75Gy exclusive DEGs of 2 and 6 weeks presented inflammation and fibrosis-related biological process, respectively. These include anti-inflammatory process, cytokine production, EMT, vasculogenesis, and angiogenesis. These results suggested that 65Gy maybe a better dose for delivering less exaggerated, clinically relevant inflammation and fibrotic events, and thus, it can be utilised in establishing appropriate preclinical models for studying RIPF pathology and therapy.

Dataset Information

Natural flavonoids exhibit potent anticancer activity by targeting microRNAs in cancer: A signature step hinting towards clinical perfection.

Publications

Natural flavonoids exhibit potent anticancer activity by targeting microRNAs in cancer: A signature step hinting towards clinical perfection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets