Epigenetic drugs for cancer treatment and prevention: mechanisms of action

2010 ◽  
Vol 1 (3-4) ◽  
pp. 239-251 ◽  
Author(s):  
Xiao-Dan Yu ◽  
Z. Sheng Guo
Keyword(s):  
Cell Death ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Mechanisms Of Action ◽  
Mitotic Catastrophe ◽  
Epigenetic Therapy ◽  
Epigenetic Mechanisms ◽  
Epigenetic Drugs ◽  
Treatment And Prevention

AbstractThis review provides a brief overview of the basic principles of epigenetic gene regulation and then focuses on recent development of epigenetic drugs for cancer treatment and prevention with an emphasis on the molecular mechanisms of action. The approved epigenetic drugs are either inhibitors of DNA methyltransferases or histone deacetylases (HDACs). Future epigenetic drugs could include inhibitors for histone methyltransferases and histone demethylases and other epigenetic enzymes. Epigenetic drugs often function in two separate yet interrelated ways. First, as epigenetic drugs per se, they modulate the epigenomes of premalignant and malignant cells to reverse deregulated epigenetic mechanisms, leading to an effective therapeutic strategy (epigenetic therapy). Second, HDACs and other epigenetic enzymes also target non-histone proteins that have regulatory roles in cell proliferation, migration and cell death. Through these processes, these drugs induce cancer cell growth arrest, cell differentiation, inhibition of tumor angiogenesis, or cell death via apoptosis, necrosis, autophagy or mitotic catastrophe (chemotherapy). As they modulate genes which lead to enhanced chemosensitivity, immunogenicity or dampened innate antiviral response of cancer cells, epigenetic drugs often show better efficacy when combined with chemotherapy, immunotherapy or oncolytic virotherapy. In chemoprevention, dietary phytochemicals such as epigallocatechin-3-gallate and sulforaphane act as epigenetic agents and show efficacy by targeting both cancer cells and the tumor microenvironment. Further understanding of how epigenetic mechanisms function in carcinogenesis and cancer progression as well as in normal physiology will enable us to establish a new paradigm for intelligent drug design in the treatment and prevention of cancer.

scholarly journals Oncolytic Viruses and Cancer, Do You Know the Main Mechanism?

2021 ◽  
Vol 11 ◽  
Author(s):  
Wesam Kooti ◽  
Hadi Esmaeili Gouvarchin Ghaleh ◽  
Mahdieh Farzanehpour ◽  
Ruhollah Dorostkar ◽  
Bahman Jalali Kondori ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Antitumor Immunity ◽  
Malignant Tumors ◽  
Mechanisms Of Action ◽  
Oncolytic Viruses ◽  
Global Rate ◽  
Recent Developments ◽  
Review Study

The global rate of cancer has increased in recent years, and cancer is still a threat to human health. Recent developments in cancer treatment have yielded the understanding that viruses have a high potential in cancer treatment. Using oncolytic viruses (OVs) is a promising approach in the treatment of malignant tumors. OVs can achieve their targeted treatment effects through selective cell death and induction of specific antitumor immunity. Targeting tumors and the mechanism for killing cancer cells are among the critical roles of OVs. Therefore, evaluating OVs and understanding their precise mechanisms of action can be beneficial in cancer therapy. This review study aimed to evaluate OVs and the mechanisms of their effects on cancer cells.

scholarly journals Current and Emerging Biomarkers of Cell Death in Human Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Kongning Li ◽  
Deng Wu ◽  
Xi Chen ◽  
Ting Zhang ◽  
Lu Zhang ◽  
...  
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Research Area ◽  
Human Diseases ◽  
Mitotic Catastrophe ◽  
Regulated Necrosis ◽  
Early Diagnose ◽  
Multicellular Organisms ◽  
The Relationship ◽  
Made In

Cell death is a critical biological process, serving many important functions within multicellular organisms. Aberrations in cell death can contribute to the pathology of human diseases. Significant progress made in the research area enormously speeds up our understanding of the biochemical and molecular mechanisms of cell death. According to the distinct morphological and biochemical characteristics, cell death can be triggered by extrinsic or intrinsic apoptosis, regulated necrosis, autophagic cell death, and mitotic catastrophe. Nevertheless, the realization that all of these efforts seek to pursue an effective treatment and cure for the disease has spurred a significant interest in the development of promising biomarkers of cell death to early diagnose disease and accurately predict disease progression and outcome. In this review, we summarize recent knowledge about cell death, survey current and emerging biomarkers of cell death, and discuss the relationship with human diseases.

scholarly journals Promotion of Cell Death in Cisplatin-Resistant Ovarian Cancer Cells through KDM1B-DCLRE1B Modulation

2019 ◽  
Vol 20 (10) ◽  
pp. 2443 ◽  
Author(s):  
Yeon Kyu Lee ◽  
Jinyeong Lim ◽  
So Young Yoon ◽  
Jong Cheon Joo ◽  
Soo Jung Park ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Ovarian Cancer Cells ◽  
Repair Gene ◽  
Gynecological Malignancy ◽  
Downstream Target ◽  
Dna Repair Gene ◽  
Cisplatin Sensitivity

Ovarian cancer is the gynecological malignancy with the poorest prognosis, in part due to its high incidence of recurrence. Platinum agents are widely used as a first-line treatment against ovarian cancer. Recurrent tumors, however, frequently demonstrate acquired chemo-resistance to platinum agent toxicity. To improve chemo-sensitivity, combination chemotherapy regimens have been investigated. This study examined anti-tumor effects and molecular mechanisms of cytotoxicity of Oldenlandia diffusa (OD) extracts on ovarian cancer cells, in particular, cells resistant to cisplatin. Six ovarian cancer cells including A2780 and cisplatin-resistant A2780 (A2780cis) as representative cell models were used. OD was extracted with water (WOD) or 50% methanol (MOD). MOD significantly induced cell death in both cisplatin-sensitive cells and cisplatin-resistant cells. The combination treatment of MOD with cisplatin reduced viability in A2780cis cells more effectively than treatment with cisplatin alone. MOD in A2780cis cells resulted in downregulation of the epigenetic modulator KDM1B and the DNA repair gene DCLRE1B. Transcriptional suppression of KDM1B and DCLRE1B induced cisplatin sensitivity. Knockdown of KDM1B led to downregulation of DCLRE1B expression, suggesting that DCLRE1B was a KDM1B downstream target. Taken together, OD extract effectively promoted cell death in cisplatin-resistant ovarian cancer cells under cisplatin treatment through modulating KDM1B and DCLRE1B.

scholarly journals Molecular mechanisms of action and prediction of response to oxaliplatin in colorectal cancer cells

2004 ◽  
Vol 91 (11) ◽  
pp. 1931-1946 ◽  
Author(s):  
D Arango ◽  
A J Wilson ◽  
Q Shi ◽  
G A Corner ◽  
M J Arañes ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Mechanisms Of Action ◽  
Prediction Of Response ◽  
Colorectal Cancer Cells

scholarly journals Hyperthermia has Consistently Improved the Efficacy of Radiotherapy and Chemotherapy for Many Types of Cancers

2019 ◽  
Vol 1 (1) ◽  
pp. 01-05
Author(s):  
Kokkula Pavan Kumar ◽  
Prasad Garrepally
Keyword(s):  
Cancer Treatment ◽  
Cancer Cells ◽  
Mechanisms Of Action ◽  
Tumor Initiation ◽  
Large Role ◽  
Conventional Radiotherapy ◽  
Different Types

Cancer stem-like cells (CSCs) are a subset of cancer cells that are resistant to conventional radiotherapy and chemotherapy. As such, CSCs have been recognized as playing a large role in tumor initiation and recurrence. Although hyperthermia is broadly used in cancer treatment either alone or in combination with radio- or chemo-therapy, its potential to target CSCs is not well understood. In this review, we discuss different types of hyperthermia and potential mechanisms of action in cancer treatment, particularly in regards to killing CSCs.

scholarly journals Inhibition of Autophagy by Deguelin Sensitizes Pancreatic Cancer Cells to Doxorubicin

2016 ◽  
Author(s):  
Xiao-Dong Xu ◽  
Yan Zhao ◽  
Min Zhang ◽  
Rui-Zhi He ◽  
Xiu-Hui Shi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Combined Treatment ◽  
Protective Role ◽  
Pancreatic Cancer Cells ◽  
Effective Therapeutic Strategy ◽  
Cancer Experience

Pancreatic cancer is the fourth most common cause of cancer mortality worldwide. Furthermore, patients with pancreatic cancer experience limited benefit from current chemotherapeutic approaches because of drug resistance. Therefore, an effective therapeutic strategy for patients with pancreatic cancer is urgently required. Deguelin is a natural chemopreventive drug that exerts potent antiproliferative activity in solid tumors by inducing cell death. However, the molecular mechanisms underlying this activity have not been fully elucidated. Here we show that deguelin blocks autophagy and induces apoptosis in pancreatic cancer cells in vitro. Autophagy induced by doxorubicin plays a protective role in pancreatic cancer cells, and suppressing autophagy by chloroquine or silencing autophagy protein 5 enhanced doxorubicin-induced cell death. Similarly, inhibition of autophagy by deguelin also chemosensitized pancreatic cancer cell lines to doxorubicin. These findings suggest that deguelin has potent anticancer effects against pancreatic cancer and potentiates the anti-cancer effects of doxorubicin. These findings provide evidence that combined treatment with deguelin and doxorubicin represents an effective strategy for treating pancreatic cancer.

Emerging Therapeutic Targets in Oncologic Photodynamic Therapy

2019 ◽  
Vol 24 (44) ◽  
pp. 5268-5295 ◽  
Author(s):  
Gina Manda ◽  
Mihail E. Hinescu ◽  
Ionela V. Neagoe ◽  
Luis F.V. Ferreira ◽  
Rica Boscencu ◽  
...  
Keyword(s):  
Cell Death ◽  
Photodynamic Therapy ◽  
Singlet Oxygen ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Molecular Networks ◽  
Systems Medicine ◽  
Therapeutic Tools

Background:Reactive oxygen species sustain tumorigenesis and cancer progression through deregulated redox signalling which also sensitizes cancer cells to therapy. Photodynamic therapy (PDT) is a promising anti-cancer therapy based on a provoked singlet oxygen burst, exhibiting a better toxicological profile than chemo- and radiotherapy. Important gaps in the knowledge on underlining molecular mechanisms impede on its translation towards clinical applications.Aims and Methods:The main objective of this review is to critically analyse the knowledge lately gained on therapeutic targets related to redox and inflammatory networks underlining PDT and its outcome in terms of cell death and resistance to therapy. Emerging therapeutic targets and pharmaceutical tools will be documented based on the identified molecular background of PDT.Results:Cellular responses and molecular networks in cancer cells exposed to the PDT-triggered singlet oxygen burst and the associated stresses are analysed using a systems medicine approach, addressing both cell death and repair mechanisms. In the context of immunogenic cell death, therapeutic tools for boosting anti-tumor immunity will be outlined. Finally, the transcription factor NRF2, which is a major coordinator of cytoprotective responses, is presented as a promising pharmacologic target for developing co-therapies designed to increase PDT efficacy.Conclusion:There is an urgent need to perform in-depth molecular investigations in the field of PDT and to correlate them with clinical data through a systems medicine approach for highlighting the complex biological signature of PDT. This will definitely guide translation of PDT to clinic and the development of new therapeutic strategies aimed at improving PDT.

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