Identification of key genes of hesperidin in inhibition of breast cancer stem cells by functional network analysis

Hermawan, Adam; Khumaira, Annisa; Ikawati, Muthi; Putri, Herwandhani; Jenie, Riris Istighfari; Angraini, Sonia Meta; Muflikhasari, Haruma Anggraini

doi:10.1016/j.compbiolchem.2020.107427

Cited by 17 publications

(13 citation statements)

References 56 publications

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“…Furthermore, among the five THs (i.e., AKT1 , ataxia-telangiectasia mutated kinase [ ATM ], CDK1 , beta-catenin [ CTNNB1 ] and TP53 ) chosen for genetic alteration analysis, TP53 genetic alterations could particularly be found in 39% of BC patients. Overall, the in vitro and in silico findings suggest that hesperidin is likely to inhibit BCSCs by targeting p53 ( Hermawan et al, 2021 ), whose mutations have been associated with a higher aggressiveness and a lower overall survival in BC ( Gasco et al, 2002 ).…”

Section: Chemotherapeutic Activities Of Hesperidin and Hesperetinmentioning

confidence: 94%

“… Hermawan et al (2021) investigated the effect of hesperidin on MCF-7 mammospheres (3D) that exhibit enriched BCSC properties, as confirmed via the observation of significantly upregulated cancer stem cell markers (i.e., nanog homeobox [ NANOG ] and aldehyde dehydrogenase 1 [ ALDH1 ]) in the mammospheres. A series of in vitro experiments revealed that hesperidin inhibited mammosphere and colony formation as well as exerted cytotoxic and anti-migratory effects against mammosphere-derived MCF-7 cells (3D).…”

Section: Chemotherapeutic Activities Of Hesperidin and Hesperetinmentioning

confidence: 99%

“…In the same study, both in vitro and in silico approaches were employed to elucidate the underlying molecular mechanisms of the inhibitory effect of hesperidin on BCSCs ( Hermawan et al, 2021 ). Effects of heperidin on the gene expression of the markers for EMT (i.e., MMP-9), stemness (i.e., ALDH1 and p53), cell cycle (i.e., p21 and cyclin D1) and apoptosis (i.e., Bcl-2) were evaluated in vitro .…”

Section: Chemotherapeutic Activities Of Hesperidin and Hesperetinmentioning

confidence: 99%

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Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects

Yap

Sekar

et al. 2021

Saudi Journal of Biological Sciences

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Breast cancer (BC) has high incidence and mortality rates, making it a major global health issue. BC treatment has been challenging due to the presence of drug resistance and the limited availability of therapeutic options for triple-negative and metastatic BC, thereby urging the exploration of more effective anti-cancer agents. Hesperidin and its aglycone hesperetin, two flavonoids from citrus species, have been extensively evaluated for their anti-cancer potentials. In this review, available literatures on the chemotherapeutic and chemosensitising activities of hesperidin and hesperetin in preclinical BC models are reported. The safety and bioavailability of hesperidin and hesperetin as well as the strategies to enhance their bioavailability are also discussed. Overall, hesperidin and hesperetin can inhibit cell proliferation, migration and BC stem cells as well as induce apoptosis and cell cycle arrest in vitro . They can also inhibit tumour growth, metastasis and neoplastic changes in tissue architecture in vivo . Moreover, the co-administration of hesperidin or hesperetin with doxorubicin, letrozole or tamoxifen can enhance the efficacies of these clinically available agents. These chemotherapeutic and chemosensitising activities of hesperidin and hesperetin have been linked to several mechanisms, including the modulation of signalling pathways, glucose uptake, enzymes, miRNA expression, oxidative status, cell cycle regulatory proteins, tumour suppressor p53, plasma and liver lipid profiles as well as DNA repair mechanisms. However, poor water solubility, extensive phase II metabolism and apical efflux have posed limitations to the bioavailability of hesperidin and hesperetin. Various strategies for bioavailability enhancement have been studied, including the utilisation of nano-based drug delivery systems and the co-administration of hesperetin with other flavonoids. In particular, nanoformulated hesperidin and hesperetin possess greater chemotherapeutic and chemosensitising activities than free compounds. Despite promising preclinical results, further safety and efficacy evaluation of hesperidin and hesperetin as well as their nanoformulations in clinical trials is required to ascertain their potentials to be developed as clinically useful agents for BC treatment.

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Section: Chemotherapeutic Activities Of Hesperidin and Hesperetinmentioning

confidence: 94%

Section: Chemotherapeutic Activities Of Hesperidin and Hesperetinmentioning

confidence: 99%

Section: Chemotherapeutic Activities Of Hesperidin and Hesperetinmentioning

confidence: 99%

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Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects

Yap

Sekar

et al. 2021

Saudi Journal of Biological Sciences

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“…Recently, Hermawan et al (2021) reported the anticancer activity of hesperidin in luminal A-derived breast cancer spheroids using bioinformatics and an in vitro approach. A decreased sphere and colony formation potential was observed in hesperidin-treated MCF-7 cells [ 90 ].…”

Section: Other Dietary Phytochemicalsmentioning

confidence: 99%

Targeting Breast Cancer-Derived Stem Cells by Dietary Phytochemicals: A Strategy for Cancer Prevention and Treatment

Prajapati

Gupta

Kumar

2022

Cancers

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Breast cancer is heterogeneous disease with variable prognosis and therapeutic response. Approximately, 70% of diagnosed breast cancer represents the luminal A subtype. This subpopulation has a fair prognosis with a lower rate of relapse than the other clinical subtypes. Acquisition of stemness in luminal A subtype modifies the phenotype plasticity to accomplish increased aggressiveness and therapeutic resistance. Therefore, targeting luminal A-derived breast cancer stem cells (BCSCs) could be a promising strategy for its prevention and treatment. Extensive studies reveal that dietary phytochemicals have the potential to target BCSCs by modulating the molecular and signal transduction pathways. Dietary phytochemicals alone or in combination with standard therapeutic modalities exert higher efficacy in targeting BCSCs through changes in stemness, self-renewal properties and hypoxia-related factors. These combinations offer achieving higher radio- and chemo- sensitization through alteration in the key signaling pathways such as AMPK, STAT3, NF-ĸB, Hedgehog, PI3K/Akt/mTOR, Notch, GSK3β, and Wnt related to cancer stemness and drug resistance. In this review, we highlight the concept of targeting luminal A-derived BCSCs with dietary phytochemicals by summarizing the pathways and underlying mechanism(s) involved during therapeutic resistance.

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“…Gene ontology, especially the cellular component category, and KEGG pathway analysis of proteins contributing to metastasis were evaluated using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) v6.8. (Huang et al, 2009), with p < 0.05 applied as the threshold for significance (Hermawan et al, 2021).…”

Section: Go and Kegg Pathway Enrichment Analysismentioning

confidence: 99%

Exploring the Potency of Jatropha Seed Meal (Jatropha curcas) as a Chemoprevention Agent through Metastatic Inhibition

Nangimi

Tafrihani²,

Adisusilo³

et al. 2022

Indonesian J Pharm

Self Cite

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Jatropha (Jatropha curcas) is often used as biodiesel because of the oil content in its seeds. The production of jatropha oil generates a byproduct in the form of jatropha seed meal, which contains compounds with cytotoxic activity and phorbol esters, as co-carcinogens and tumor promoters. Meanwhile, metastasis is one of the characteristics of cancer where the cells spread to another tissue. This study aimed to determine the potential of jatropha seed meal as a chemoprevention agent, particularly an antimetastatic one, under bioinformatic study and molecular docking. Genecards and DAVID were performed to explore the protein involved in the metastatic process and its gene ontology. The prediction target protein was caught by SwissTargetPrediction. Jatropha seed meal showed the presence of isoamericanol A, myricetin, daidzein, gallic acid, and rutin. There are 11 prediction target proteins correlated to metastatic in extracellular matrix components. Then we were docked to a protein involved in metastasis, matrix metalloproteinase (MMP)-9 (PDB ID: 6ESM) using MOE software. The docking score determined the interaction properties. The docking analysis revealed that isoamericanol A, daidzein, and myricetin exhibited better binding affinity than native ligands and other compounds. Moreover, based on our literature study, the jatropha seed meal contains isoamericanol A, rutin, myricetin, daidzein, and gallic acid, which present anticancer properties by inhibition of cell invasion and migration, cell cycle arrest induction, and suppression of the MMP-9 activity. Overall, jatropha seed meal has potential as an antimetastatic agent. A comprehensive study is needed to explore the possibility of developing it as a supportive agent in combination with a chemotherapeutic agent.

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Identification of key genes of hesperidin in inhibition of breast cancer stem cells by functional network analysis

Cited by 17 publications

References 56 publications

Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects

Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects

Targeting Breast Cancer-Derived Stem Cells by Dietary Phytochemicals: A Strategy for Cancer Prevention and Treatment

Exploring the Potency of Jatropha Seed Meal (Jatropha curcas) as a Chemoprevention Agent through Metastatic Inhibition

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