Genistein nanoformulation promotes selective apoptosis in oral squamous cell carcinoma through repression of 3PK-EZH2 signalling pathway

Dev, Atul; Sardoiwala, Mohammed Nadim; Kushwaha, Avinash Chandra; Karmakar, Surajit; Choudhury, Subhasree Roy

doi:10.1016/j.phymed.2020.153386

Cited by 33 publications

(21 citation statements)

References 25 publications

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“…GLNPs administration enhanced ROS production followed by BAX expression and activation of caspase-3 in JHU011 and L929 fibroblast cell lines of OSCC. GLNPs also directly targeted the EZH2 via suppression of the expression of 3PK and enhanced bioavailability, biocompatibility and distribution of genistein in vivo [ 93 ]. Intestinal absorption of genistein was attempted to improve by loading it in solid lipid nanoparticles (SLN).…”

Section: Introductionmentioning

confidence: 99%

Genistein as a regulator of signaling pathways and microRNAs in different types of cancers

et al. 2021

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Cancers are complex diseases orchestrated by a plethora of extrinsic and intrinsic factors. Research spanning over several decades has provided better understanding of complex molecular interactions responsible for the multifaceted nature of cancer. Recent advances in the field of next generation sequencing and functional genomics have brought us closer towards unravelling the complexities of tumor microenvironment (tumor heterogeneity) and deregulated signaling cascades responsible for proliferation and survival of tumor cells. Phytochemicals have begun to emerge as potent beneficial substances aimed to target deregulated signaling pathways. Isoflavonoid genistein is an essential phytochemical involved in regulation of key biological processes including those in different types of cancer. Emerging preclinical evidence have shown its anti-cancer, anti-inflammatory and anti-oxidant properties. Testing of this substance is in various phases of clinical trials. Comprehensive preclinical and clinical trials data is providing insight on genistein as a modulator of various signaling pathways both at transcription and translation levels. In this review we have explained the mechanistic regulation of several key cellular pathways by genistein. We have also addressed in detail various microRNAs regulated by genistein in different types of cancer. Moreover, application of nano-formulations to increase the efficiency of genistein is also discussed. Understanding the pleiotropic potential of genistein to regulate key cellular pathways and development of efficient drug delivery system will bring us a step towards designing better chemotherapeutics.

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Section: Introductionmentioning

confidence: 99%

Genistein as a regulator of signaling pathways and microRNAs in different types of cancers

et al. 2021

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“…This ICG-tagged stable nanosized complex not only allowed the visualization of the expression of EZH2 in the engrafted tumor in a leukemia mouse model but also could inhibit tumor growth by targeting EZH2. Some other studies have also confirmed the feasibility of epigenetic regulation-based strategies for precision treatment of cancer (Dev et al 2021;Kushwaha et al 2020;Sardoiwala et al 2020).…”

Section: Histone Methylationmentioning

confidence: 77%

Optical Imaging of Epigenetic Modifications in Cancer: A Systematic Review

Zhang

Liu

et al. 2022

Phenomics

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Increasing evidence has demonstrated that abnormal epigenetic modifications are strongly related to cancer initiation. Thus, sensitive and specific detection of epigenetic modifications could markedly improve biological investigations and cancer precision medicine. A rapid development of molecular imaging approaches for the diagnosis and prognosis of cancer has been observed during the past few years. Various biomarkers unique to epigenetic modifications and targeted imaging probes have been characterized and used to discriminate cancer from healthy tissues, as well as evaluate therapeutic responses. In this study, we summarize the latest studies associated with optical molecular imaging of epigenetic modification targets, such as those involving DNA methylation, histone modification, noncoding RNA regulation, and chromosome remodeling, and further review their clinical application on cancer diagnosis and treatment. Lastly, we further propose the future directions for precision imaging of epigenetic modification in cancer. Supported by promising clinical and preclinical studies associated with optical molecular imaging technology and epigenetic drugs, the central role of epigenetics in cancer should be increasingly recognized and accepted.

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“…(23). Nanoparticle-mediated delivery is a promising approach to enhance bioavailability and increase the efficacy of several chemopreventive agents for OSCC (24)(25)(26)(27)(28). Our previous study clearly demonstrated that nano-SAB can enhance cellular uptake and anticancer efficacy in head and neck cancer cells, as well as in precancerous cells in vitro (8).…”

Section: Discussionmentioning

confidence: 99%

Chemopreventive efficacy of salvianolic acid B phospholipid complex loaded nanoparticles against experimental oral carcinogenesis: implication of sustained drug release

Liu¹,

Zhou²,

Zhu³

et al. 2022

Ann Transl Med

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Background: Although we have previously demonstrated that phospholipid complex loaded nanoparticles (PLC-NPs) encapsulating salvianolic acid B (SAB) can enhance anticancer activity in head and neck cancer and precancerous cells in vitro, the chemopreventive efficacy of SAB-PLC-NPs (nano-SAB) in vivo remains unclear. Here, we aimed to investigate the in vivo efficacy of nano-SAB against experimental oral carcinogenesis.Methods: Oral tongue carcinogenesis was induced in C57BL/6 mice through the administration of 4-nitroquinoline-N-oxide (4NQO, 100 μg/mL) in drinking water for 22 weeks. To preliminarily evaluate the effect of sustained drug release against oral carcinogenesis, free-or nano-SAB (16.6 mg/kg/d) was administered orally for 18 weeks, and the treatment was discontinued for the remaining 4 weeks.Results: Histological evaluation revealed a significant (P<0.05) decrease in the incidence of carcinoma in free-SAB-treated (16.7%) and nano-SAB-treated (10.0%) mice compared to mice exposed to 4NQO alone (34.3%). A decrease in carcinoma growth rate was also observed in free-SAB-treated (12.2%) and nano-SAB-treated (5.5%) mice compared to the 4NQO-exposed group (18.3%), even after drug withdrawal for 4 weeks. Immunohistochemical analysis revealed that nano-SAB treatment effectively suppressed Ki-67, proliferative cell nuclear antigen (PCNA), and cyclin D1 expression in high-risk dysplastic lesions compared to free-SAB-treated and 4NQO-exposed groups (all P<0.05). Importantly, nano-SAB maintained low levels of Ki-67, PCNA, and cyclin D1 expression even after drug withdrawal for 4 weeks.Conclusions: Together with our previous in vitro data, this in vivo study confirms that nano-SAB has superior chemopreventive efficacy by promoting more potent anti-proliferation and cell cycle arrest responses. These findings demonstrate the potential of SAB-PLC-NPs as promising chemopreventive agents for treating oral carcinogenesis.

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Genistein nanoformulation promotes selective apoptosis in oral squamous cell carcinoma through repression of 3PK-EZH2 signalling pathway

Cited by 33 publications

References 25 publications

Genistein as a regulator of signaling pathways and microRNAs in different types of cancers

Genistein as a regulator of signaling pathways and microRNAs in different types of cancers

Optical Imaging of Epigenetic Modifications in Cancer: A Systematic Review

Chemopreventive efficacy of salvianolic acid B phospholipid complex loaded nanoparticles against experimental oral carcinogenesis: implication of sustained drug release

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