Targeting cancer stem cell pathways for cancer therapy

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

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Bioactive natural products in cancer prevention and therapy: Progress and promise

Seminars in Cancer Biology, Journal Year: 2016, Volume and Issue: 40-41, P. 1 - 3

Published: Aug. 25, 2016

Language: Английский

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Chemoresistance mechanisms of breast cancer and their countermeasures

Biomedicine & Pharmacotherapy, Journal Year: 2019, Volume and Issue: 114, P. 108800 - 108800

Published: March 26, 2019

Chemoresistance is one of the major challenges for breast cancer treatment. Owing to its heterogeneous nature, chemoresistance mechanisms are complicated, and not been fully elucidated. The existing treatments fall short offering adequate solution drug resistance, so more effective approaches desperately needed improve therapeutic regimens. To overcome this hurdle, a number strategies being investigated, such as novel agents or carriers combination In addition, some new therapeutics including gene therapy immunotherapy may be promising dealing with resistance. article, we review in cancer. Furthermore, potential methods resistance were discussed.

Language: Английский

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Natural Products for the Management and Prevention of Breast Cancer

Evidence-based Complementary and Alternative Medicine, Journal Year: 2018, Volume and Issue: 2018, P. 1 - 23

Published: Jan. 1, 2018

Among all types of cancer, breast cancer is one the most challenging diseases, which responsible for a large number related deaths. Hormonal therapy, surgery, chemotherapy, and radiotherapy have been used as treatment very long time. Due to severe side effects multidrug resistance, these approaches become increasingly ineffective. However, adoption complementary approach can be big solution this situation, it evident that compounds derived from natural source great deal anticancer activity. Natural fight against aggressiveness inhibit cancerous cell proliferation, modulate pathways. A research works are now focusing on dietary trying find out new more effective strategies patients. In review, we discussed some significant chemical with their mechanisms actions, potent by proper modifications further clinical research. Future anti-breast-cancer agents open horizon in treatment, will play role enhancing survival rate

Language: Английский

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Exosome-Based Cancer Therapy: Implication for Targeting Cancer Stem Cells

Frontiers in Pharmacology, Journal Year: 2017, Volume and Issue: 7

Published: Jan. 12, 2017

Drug resistance, difficulty in specific targeting and self-renewal properties of cancer stem cells (CSCs) all contribute to treatment failure relapse. CSCs have been suggested as both the seeds primary cancer, roots chemo- radio-therapy resistance. The ability precisely deliver drugs target is an urgent need for therapy, with nanotechnology-based drug delivery system being one most promising tools achieve this clinic. Exosomes are cell-derived natural nanometric vesicles that widely distributed body fluids involved multiple disease processes, including tumorigenesis. Exosome-based vehicles a number advantages: they non-toxic, non-immunogenic, can be engineered robust capacity specificity. This enables exosomes powerful nanocarrier anti-cancer genes CSC therapy. Here, we will introduce current explorations exosome-based particular focus on several exosomal engineering approaches improved their efficiency specificity targeting.

Language: Английский

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A new inhibitor of glucose-6-phosphate dehydrogenase blocks pentose phosphate pathway and suppresses malignant proliferation and metastasis in vivo

Cell Death and Disease, Journal Year: 2018, Volume and Issue: 9(5)

Published: May 14, 2018

Abstract Pentose phosphate pathway (PPP) is a major glucose metabolism pathway, which has fundamental role in cancer growth and metastasis. Even though PPP blockade been pointed out as very promising strategy against cancer, effective anti-PPP agents are not still available the clinical setting. Here we demonstrate that natural molecule polydatin inhibits glucose-6-phosphate dehydrogenase (G6PD), key enzyme of PPP. Polydatin blocks G6PD causing accumulation reactive oxygen species strong increase endoplasmic reticulum stress. These effects followed by cell cycle block S phase, an about 50% apoptosis, 60% inhibition invasion vitro. Accordingly, orthotopic metastatic model tongue 100 mg/kg induced 30% tumor size reduction with 80% lymph node metastases ( p < 0.005). toxic animals up to dose 200 phase II trial shows it also well tolerated humans (40 mg twice day for 90 days). Thus, may be used reliable tool limit human spread.

Language: Английский

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Resveratrol-induced autophagy and apoptosis in cisplatin-resistant human oral cancer CAR cells: A key role of AMPK and Akt/mTOR signaling

International Journal of Oncology, Journal Year: 2017, Volume and Issue: 50(3), P. 873 - 882

Published: Jan. 30, 2017

Resveratrol is known to be an effective chemo­preventive phytochemical against multiple tumor cells. However, the increasing drug resistance avoids cancer treatment in oral cavity cancer. In this study, we investigated antitumor activity of resveratrol and its mechanism cisplatin-resistant human CAR Our results demonstrated that had extremely low toxicity normal cells provoked autophagic cell death form acidic vesicular organelles (AVOs) vacuoles by acridine orange (AO) monodansylcadaverine (MDC) staining. Either DNA fragmentation or condensation occurred resveratrol-triggered apoptosis. These inhibitors PI3K class III (3-MA) AMP-activated protein kinase (AMPK) (compound c) suppressed vesicle formation, LC3-II levels autophagy induced resveratrol. The pan-caspase inhibitor Z-VAD-FMK attenuated cleaved caspase-9, caspase-3 also enhanced phosphorylation AMPK regulated autophagy- pro-apoptosis-related signals resveratrol-treated Importantly, stimulated mRNA gene expression, including Atg5, Atg12, Beclin-1 Overall, our findings indicate likely induce apoptotic drug-resistant might become a new approach for near future.

Language: Английский

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Breast cancer heterogeneity and its implication in personalized precision therapy

Experimental Hematology and Oncology, Journal Year: 2023, Volume and Issue: 12(1)

Published: Jan. 9, 2023

Abstract Breast cancer heterogeneity determines progression, treatment effects, and prognosis. However, the precise mechanism for this remains unknown owing to its complexity. Here, we summarize origins of breast influence on disease recurrence, therapeutic resistance. We review possible mechanisms research methods used analyze it. also highlight importance cell interactions heterogeneity, which can be further categorized into cooperative competitive interactions. Finally, provide new insights individual treatments based heterogeneity.

Language: Английский

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An Updated Review of Tetrodotoxin and Its Peculiarities

Marine Drugs, Journal Year: 2022, Volume and Issue: 20(1), P. 47 - 47

Published: Jan. 3, 2022

Tetrodotoxin (TTX) is a crystalline, weakly basic, colorless organic substance and one of the most potent marine toxins known. Although TTX was first isolated from pufferfish, it has been found in numerous other organisms few terrestrial species. Moreover, tetrodotoxication still an important health problem today, as no known antidote. poisonings were commonly reported Japan, Thailand, China, but today risk poisoning spreading around world. Recent studies have shown that TTX-containing fish are being regions Pacific Indian Ocean, well Mediterranean Sea. This review aims to summarize pertinent information available date on structure, origin, distribution, mechanism action analytical methods used for detection TTX, organisms, symptoms poisoning, incidence worldwide.

Language: Английский

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Natural Small Molecules in Breast Cancer Treatment: Understandings from a Therapeutic Viewpoint

Molecules, Journal Year: 2022, Volume and Issue: 27(7), P. 2165 - 2165

Published: March 27, 2022

Breast cancer (BrCa) is the most common malignancy in women and second significant cause of death from cancer. BrCa one challenging malignancies to treat, it accounts for a large percentage cancer-related deaths. The number cases requiring more effective therapy has increased dramatically. Scientists are looking productive agents, such as organic combinations, prevention treatment because chemotherapeutic agents linked metastasis, resistance drugs, side effects. Natural compounds produced by living organisms promote apoptosis inhibit slowing spread As result, these may delay BrCa, enhancing survival rates reducing deaths caused BrCa. Several natural production while lowering cell proliferation triggering death. compounds, addition therapeutic approaches, efficient potential treating This review highlights demonstrated various studies have anticancer properties cells. Future research into biological anti-BrCa pave way new era treatment, with drugs playing key role improving patient rates.

Language: Английский

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