Targeting Colorectal Cancer Proliferation, Stemness and Metastatic Potential Using Brassicaceae Extracts Enriched in Isothiocyanates: A 3D Cell Model-Based Study DOI Open Access
L. Pereira, Patrícia Silva, Marlene Duarte

et al.

Nutrients, Journal Year: 2017, Volume and Issue: 9(4), P. 368 - 368

Published: April 10, 2017

Colorectal cancer (CRC) recurrence is often attributable to circulating tumor cells and/or stem (CSCs) that resist conventional therapies and foster progression. Isothiocyanates (ITCs) derived from Brassicaceae vegetables have demonstrated anticancer effects in CRC, however little known about their effect CSCs initiation properties. Here we examined the of ITCs-enriched extracts watercress broccoli cell proliferation, CSC phenotype metastasis using a previously developed three-dimensional HT29 model with CSC-like traits. Both were phytochemically characterized antiproliferative monolayers was explored. Next, performed proliferation assays flow cytometry analysis spheroids treated respective main ITCs, phenethyl isothiocyanate (PEITC) sulforaphane (SFN). Soft agar relative quantitative expression stemness markers Wnt/β-catenin signaling players evaluate these phytochemicals metastasis. Our results showed both ITCs exert spheroids, arresting cycle at G2/M, possibly due ITC-induced DNA damage. Colony formation LGR5 CD133 significantly reduced. Only extract PEITC decreased ALDH1 activity dose-dependent manner, as well β-catenin expression. research provides new insights on CRC therapy ITC-enriched extracts, specially extract, target by impairing ALDH1-mediated chemo-resistance, anoikis evasion, self-renewal metastatic potential.

Language: Английский

Targeting cancer stem cell pathways for cancer therapy DOI Creative Commons
Liqun Yang, Pengfei Shi,

Gaichao Zhao

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Feb. 7, 2020

Abstract Since cancer stem cells (CSCs) were first identified in leukemia 1994, they have been considered promising therapeutic targets for therapy. These self-renewal capacity and differentiation potential contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, OCT4, Sox2, Nanog, KLF4, MYC. In addition, many intracellular signaling pathways, Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers activators transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target rapamycin), TGF (transforming growth factor)/SMAD, PPAR (peroxisome proliferator-activated receptor), well extracellular vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, mesenchymal cells, matrix, exosomes, shown be very important regulators CSCs. Molecules, vaccines, antibodies, CAR-T (chimeric antigen receptor T cell) developed specifically CSCs, some these factors already undergoing clinical trials. This review summarizes the characterization identification depicts major pathways that regulate CSC development, discusses targeted therapy

Language: Английский

Citations

1517
NF‐κB signaling in inflammation and cancer DOI
Tao Zhang, Chao Ma, Zhiqiang Zhang

et al.

MedComm, Journal Year: 2021, Volume and Issue: 2(4), P. 618 - 653

Published: Dec. 1, 2021

Abstract Since nuclear factor of κ‐light chain enhancer‐activated B cells (NF‐κB) was discovered in 1986, extraordinary efforts have been made to understand the function and regulating mechanism NF‐κB for 35 years, which lead significant progress. Meanwhile, molecular mechanisms activation also illuminated, cascades signaling events leading activity key components pathway are identified. It has suggested plays an important role human diseases, especially inflammation‐related diseases. These studies make attractive target disease treatment. This review aims summarize knowledge family members NF‐κB, as well basic activation. We will effects dysregulated on inflammation, tumorigenesis, tumor microenvironment. The progression translational study drug development targeting inflammatory diseases cancer treatment potential obstacles be discussed. Further investigations precise functions physiological pathological settings underlying urgent need develop drugs treatment, with minimal side effects.

Language: Английский

Citations

291
Combinatorial Epigenetics Impact of Polyphenols and Phytochemicals in Cancer Prevention and Therapy DOI Open Access
Itika Arora,

Manvi Sharma,

Trygve O. Tollefsbol

et al.

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(18), P. 4567 - 4567

Published: Sept. 14, 2019

Polyphenols are potent micronutrients that can be found in large quantities various food sources and spices. These compounds, also known as phenolics due to their phenolic structure, play a vital nutrient-based role the prevention of diseases such diabetes, cardiovascular diseases, neurodegenerative liver disease, cancers. However, function polyphenols disease therapy depends on dietary consumption biological properties. According American Cancer Society statistics, there will an expected rise 23.6 million new cancer cases by 2030. Due severity increased risk, it is important evaluate preventive measures associated with cancer. Relatively recently, numerous studies have indicated phytochemicals possess properties modifying epigenetic mechanisms modulate gene expression resulting regulation phytochemicals, when administrated dose-dependent combinatorial-based manner, enhanced effect changes, which crucial therapy. Hence, this review focus combined impact modifications DNA methylation histone well non-coding miRNAs for treatment types

Language: Английский

Citations

177
Opportunities and challenges for co-delivery nanomedicines based on combination of phytochemicals with chemotherapeutic drugs in cancer treatment DOI

Quan Gao,

Jiao Feng, Wen‐Cheng Liu

et al.

Advanced Drug Delivery Reviews, Journal Year: 2022, Volume and Issue: 188, P. 114445 - 114445

Published: July 9, 2022

Language: Английский

Citations

163
Breast cancer stem cells: Features, key drivers and treatment options DOI

Jürgen Dittmer

Seminars in Cancer Biology, Journal Year: 2018, Volume and Issue: 53, P. 59 - 74

Published: July 27, 2018

Language: Английский

Citations

155
Combating breast cancer using combination therapy with 3 phytochemicals: Piperine, sulforaphane, and thymoquinone DOI Open Access
Muhammad Zakariyyah Aumeeruddy, Mohamad Fawzi Mahomoodally

Cancer, Journal Year: 2019, Volume and Issue: 125(10), P. 1600 - 1611

Published: Feb. 27, 2019

Despite the significant advances in screening methods for early diagnosis, breast cancer remains a global threat and continues to be leading diagnosed women, requiring effective therapy. Currently, combination therapy has become hallmark of treatment due high incidence tumor recurrence disease progression after monotherapeutic treatments, including surgery, radiotherapy, endocrine therapy, chemotherapy. Over past decades, there been considerable interest studying anticancer effect bioactive phytochemicals from medicinal plants combined with these conventional therapies. The rationale this type is use combinations drugs that work by different mechanisms, thereby decreasing likelihood cells will develop resistance, also reduce therapeutic dose toxicity single treatments. Three agents have received great attention regard their properties: 1) piperine, dietary phytochemical isolated black pepper ( Piper nigrum L.) long longum L.); 2) sulforaphane, an isothiocyanate mainly derived cruciferous vegetables; 3) thymoquinone, active compound seed Nigella sativa L.). This review focused on 3 compounds objective observing enhanced efficacy compared highlights importance nanoformulation such could enhance bioavailability providing efficient targeted delivery system reduced systemic while resulting more dosing at target site.

Language: Английский

Citations

138
Metabolism-Based Therapeutic Strategies Targeting Cancer Stem Cells DOI Creative Commons
Petra Jagušt, Beatriz de Luxán‐Delgado, Beatriz Parejo-Alonso

et al.

Frontiers in Pharmacology, Journal Year: 2019, Volume and Issue: 10

Published: March 22, 2019

Cancer heterogeneity constitutes the major source of disease progression and therapy failure. Tumors comprise functionally diverse subpopulations, with cancer stem cells (CSCs) as this heterogeneity. Since these bear in vivo tumorigenicity metastatic potential, survive chemotherapy drive relapse, its elimination may be only way to achieve long-term survival patients. Thanks great advances field over last few years, we know now that cellular metabolism stemness are highly intertwined normal development cancer. Indeed, CSCs show distinct metabolic features compared their more differentiated progenies, though dominant phenotype varies across tumor entities, patients even subclones within a tumor. Following initial works focused on glucose metabolism, current studies have unveiled particularities CSC terms redox state, lipid use alternative fuels, such amino acids or ketone bodies. In review, describe different phenotypes attributed special focus metabolism-based therapeutic strategies tested preclinical clinical settings.

Language: Английский

Citations

127
Phytochemicals in cancer cell chemosensitization: Current knowledge and future perspectives DOI
Elina Khatoon, Kishore Banik, Choudhary Harsha

et al.

Seminars in Cancer Biology, Journal Year: 2020, Volume and Issue: 80, P. 306 - 339

Published: June 28, 2020

Language: Английский

Citations

123
Albumin Nanoparticle of Paclitaxel (Abraxane) Decreases while Taxol Increases Breast Cancer Stem Cells in Treatment of Triple Negative Breast Cancer DOI
Hebao Yuan, Hongwei Guo, Xin Luan

et al.

Molecular Pharmaceutics, Journal Year: 2020, Volume and Issue: 17(7), P. 2275 - 2286

Published: June 2, 2020

Triple-negative breast cancer (TNBC) has a high rate of metastasis, which is associated with stem-like cells (CSCs). Although Taxol (micelle formulation paclitaxel) the first line chemotherapy to treat TNBC, it increases CSCs in residual tumors. Abraxane, albumin nanoparticle paclitaxel, showed lower plasma concentration compared both human and animal models, but not clear why Abraxane superior efficacy treatment metastatic humans. In this study, we intend investigate if eliminates for its better efficacy. The results that similar cytotoxicity SUM149 comparison Taxol. 3- 5-fold blood drug Taxol, achieved tumor 10-fold higher tumor/plasma ratio xenograft NOD/SCID mouse model. addition, shrink size orthotopic However, decreased frequency by 9-fold, while increased an Furthermore, 15-fold intracellular uptake ALDH+ differentiated ALDH– provides mechanism Abraxane's eliminate Our data suggest may have broad implication enhance drug's eliminating stem diseases.

Language: Английский

Citations

91
Plant Natural Products: Promising Resources for Cancer Chemoprevention DOI Creative Commons
Li Ma, Mengmeng Zhang, Rong Zhao

et al.

Molecules, Journal Year: 2021, Volume and Issue: 26(4), P. 933 - 933

Published: Feb. 10, 2021

Cancer is a major factor threatening human health and life safety, there lack of safe effective therapeutic drugs. Intervention prevention in premalignant process are ways to reverse carcinogenesis prevent cancer from occurring. Plant natural products rich sources promising source for chemoprevention. This article reviews the chemopreventive effects products, especially focused on polyphenols, flavonoids, monoterpene triterpenoids, sulfur compounds, cellulose. Meanwhile, main mechanisms include induction apoptosis, antiproliferation inhibition metastasis briefly summarized. In conclusion, this provides evidence remaining prominent

Language: Английский

Citations

91