Unraveling the Potential Role of Glutathione in Multiple Forms of Cell Death in Cancer Therapy

Glutathione is the principal intracellular antioxidant buffer against oxidative stress and mainly exists in the forms of reduced glutathione (GSH) and oxidized glutathione (GSSG). The processes of glutathione synthesis, transport, utilization, and metabolism are tightly controlled to maintain intracellular glutathione homeostasis and redox balance. As for cancer cells, they exhibit a greater ROS level than normal cells in order to meet the enhanced metabolism and vicious proliferation; meanwhile, they also have to develop an increased antioxidant defense system to cope with the higher oxidant state. Growing numbers of studies have implicated that altering the glutathione antioxidant system is associated with multiple forms of programmed cell death in cancer cells. In this review, we firstly focus on glutathione homeostasis from the perspectives of glutathione synthesis, distribution, transportation, and metabolism. Then, we discuss the function of glutathione in the antioxidant process. Afterwards, we also summarize the recent advance in the understanding of the mechanism by which glutathione plays a key role in multiple forms of programmed cell death, including apoptosis, necroptosis, ferroptosis, and autophagy. Finally, we highlight the glutathione-targeting therapeutic approaches toward cancers. A comprehensive review on the glutathione homeostasis and the role of glutathione depletion in programmed cell death provide insight into the redox-based research concerning cancer therapeutics.

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Bioactive Compounds: Multi-Targeting Silver Bullets for Preventing and Treating Breast Cancer

Cancers ◽

10.3390/cancers11101563 ◽

2019 ◽

Vol 11 (10) ◽

pp. 1563 ◽

Cited By ~ 9

Author(s):

Nethaji Muniraj ◽

Sumit Siddharth ◽

Dipali Sharma

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Cancer Cells ◽

Bioactive Compounds ◽

Cancer Therapeutics ◽

The Body ◽

Cancer Drug ◽

Metastatic Progression ◽

Normal Cells ◽

Cancer Drug Discovery

Each cell in our body is designed with a self-destructive trigger, and if damaged, can happily sacrifice itself for the sake of the body. This process of self-destruction to safeguard the adjacent normal cells is known as programmed cell death or apoptosis. Cancer cells outsmart normal cells and evade apoptosis and it is one of the major hallmarks of cancer. The cardinal quest for anti-cancer drug discovery (bioactive or synthetic compounds) is to be able to re-induce the so called “programmed cell death” in cancer cells. The importance of bioactive compounds as the linchpin of cancer therapeutics is well known as many effective chemotherapeutic drugs such as vincristine, vinblastine, doxorubicin, etoposide and paclitaxel have natural product origins. The present review discusses various bioactive compounds with known anticancer potential, underlying mechanisms by which they induce cell death and their preclinical/clinical development. Most bioactive compounds can concurrently target multiple signaling pathways that are important for cancer cell survival while sparing normal cells hence they can potentially be the silver bullets for targeting cancer growth and metastatic progression.

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Revisiting Mitochondria Scored Cancer Progression and Metastasis

Cancers ◽

10.3390/cancers13030432 ◽

2021 ◽

Vol 13 (3) ◽

pp. 432

Author(s):

Rohit Gundamaraju ◽

Wenying Lu ◽

Rishya Manikam

Keyword(s):

Cell Death ◽

Cancer Cells ◽

Cancer Progression ◽

Cancer Biology ◽

Translational Regulation ◽

Focal Point ◽

Cancer Therapeutics ◽

Cancer Stemness ◽

The Warburg Effect

The Warburg effect has immensely succored the study of cancer biology, especially in highlighting the role of mitochondria in cancer stemness and their benefaction to the malignancy of oxidative and glycolytic cancer cells. Mitochondrial genetics have represented a focal point in cancer therapeutics due to the involvement of mitochondria in programmed cell death. The mitochondrion has been well established as a switch in cell death decisions. The mitochondrion’s instrumental role in central bioenergetics, calcium homeostasis, and translational regulation has earned it its fame in metastatic dissemination in cancer cells. Here, we revisit and review mechanisms through which mitochondria influence oncogenesis and metastasis by underscoring the oncogenic mitochondrion that is capable of transferring malignant capacities to recipient cells.

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Preparing Professionals in Cancer Therapy

Evolving Corporate Education Strategies for Developing Countries ◽

10.4018/978-1-4666-2845-8.ch015 ◽

2012 ◽

pp. 200-208

Author(s):

Shiv Shanker Pandey ◽

Vivek Ambastha ◽

Budhi Sagar Tiwari

Keyword(s):

Cancer Research ◽

Cell Death ◽

Cancer Therapy ◽

Programmed Cell Death ◽

Cancer Cells ◽

Western World ◽

Medical Oncologists ◽

Broad Interest ◽

Major Target

Cancer is currently the second biggest cause of death in the Western world. Cancer cells escape the normal process of programmed cell death i.e., fail to die on schedule. The ability of cancer cells to avoid programmed cell death and continue to proliferate is one of the fundamental hallmarks of cancer and is a major target of cancer therapy development. Universities and research institutes are playing a major role in progress of cancer research. The aim of this study is to attract graduates of different disciplines towards cancer research and bring together researchers from different disciplines with an interest in the role of programmed cell death in cancer therapy and exploitation of programmed cell death research for therapeutic targeting of cancer. In spite of this, it is of broad interest to make a bridge or to start collaborations in between basic researchers and medical oncologists as well as for pharmaceutical companies i.e., aim of this study is to bridging the gap between knowledge and its action or application.

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Faculty Opinions recommendation of New Arabidopsis thaliana cytochrome c partners: a look into the elusive role of cytochrome c in programmed cell death in plants.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718104360.793488383 ◽

2013 ◽

Author(s):

Daniel Gallie

Keyword(s):

Arabidopsis Thaliana ◽

Cell Death ◽

Cytochrome C ◽

Programmed Cell Death

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The role of programmed cell death ligand-1/ programmed cell death-1 (PD-L1/PD-1) in HPV-induced cervical cancer and potential for their use in blockade therapy

Current Medicinal Chemistry ◽

10.2174/0929867327666200128105459 ◽

2020 ◽

Vol 27 ◽

Cited By ~ 1

Author(s):

Lifang Zhang ◽

Yu Zhao ◽

Quanmei Tu ◽

Xiangyang Xue ◽

Xueqiong Zhu ◽

...

Keyword(s):

Cervical Cancer ◽

Cell Death ◽

Programmed Cell Death ◽

Immune Escape ◽

Hypoxia Inducible Factor ◽

Hpv Infection ◽

Advanced Cervical Cancer ◽

Cervical Carcinogenesis ◽

Programmed Cell Death 1

Background: Cervical cancer induced by infection with human papillomavirus (HPV) remains a leading cause of mortality for women worldwide although preventive vaccines and early diagnosis have reduced morbidity and mortality. Advanced cervical cancer can only be treated with either chemotherapy or radiotherapy but outcomes are poor. The median survival for advanced cervical cancer patients is only 16.8 months. Methods: We undertook a structural search of peer-reviewed published studies based on 1). Characteristics of programmed cell death ligand-1/programmed cell death-1(PD-L1/PD-1) expression in cervical cancer and upstream regulatory signals of PD-L1/PD-1 expression, 2). The role of the PD-L1/PD-1 axis in cervical carcinogenesis induced by HPV infection and 3). Whether the PD-L1/PD-1 axis has emerged as a potential target for cervical cancer therapies. Results: One hundred and twenty-six published papers were included in the review, demonstrating that expression of PD-L1/PD-1 is associated with HPV-caused cancer, especially with HPV 16 and 18 which account for approximately 70% of cervical cancer cases. HPV E5/E6/E7 oncogenes activate multiple signaling pathways including PI3K/AKT, MAPK, hypoxia-inducible factor 1α, STAT3/NF-kB and MicroRNAs, which regulate PD-L1/PD-1 axis to promote HPV-induced cervical carcinogenesis. The PD-L1/PD-1 axis plays a crucial role in immune escape of cervical cancer through inhibition of host immune response. creating an "immune-privileged" site for initial viral infection and subsequent adaptive immune resistance, which provides a rationale for therapeutic blockade of this axis in HPV-positive cancers. Currently, Phase I/II clinical trials evaluating the effects of PD-L1/PD-1 targeted therapies are in progress for cervical carcinoma, which provide an important opportunity for the application of anti-PD-L1/anti-PD-1 antibodies in cervical cancer treatment. Conclusion: Recent research developments have led to an entirely new class of drugs using antibodies against the PD-L1/PD-1 thus promoting the body’s immune system to fight the cancer. The expression and roles of the PD-L1/ PD-1 axis in the progression of cervical cancer provide great potential for using PD-L1/PD-1 antibodies as a targeted cancer therapy.

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