Potential Contributions of Antioxidants to Cancer Therapy: Immunomodulation and Radiosensitization

Thyagarajan, Anita; Sahu, Ravi P.

doi:10.1177/1534735416681639

Cited by 115 publications

(76 citation statements)

References 87 publications

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“…Recently, the intake of antioxidants has been considered as a possible strategy to improve overall health (24,25). Antioxidants play important roles in redox signaling and redox status of cells and thereby the maintenance of cellular integrity and homeostasis (26). Also, several clinical trials have suggested that antioxidants benefit cancer therapy (27).…”

Section: Discussionmentioning

confidence: 99%

Peroxiredoxin V Inhibits Emodin-induced Gastric Cancer Cell Apoptosis via the ROS/Bcl2 Pathway

Jin

Sun

Liu

et al. 2019

In Vivo

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Background/Aim: Peroxiredoxin (Prx) protein family is aberrantly expressed in various cancers including gastric cancer. Among the six family members, Prx V has been known as an antioxidant enzyme which scavenges intracellular reactive oxygen species (ROS) and modulates cellular apoptosis. This study aimed at investigating the role of Prx V in apoptosis of gastric cancer cells. Materials and Methods: Stably constructed Prx V knockdown, over-expression and mock AGS cells (a human gastric adenocarcinoma cell line) were used to study the effect of Prx V on emodin-induced apoptosis by western blotting, cell viability, apoptosis and ROS detection assays. Results: Overexpression of Prx V significantly decreased emodin-induced cellular apoptosis and ROS levels compared to Mock and Prx V knockdown AGS cells. Also, overexpression of Prx V down-regulated the expression of proapoptotic proteins, Bad and cleaved PARP, and increased the expression of anti-apoptotic protein, Bcl2. Conclusion: Prx V suppresses AGS cell apoptosis via scavenging intracellular ROS and modulating apoptosis-related markers. Gastric cancer (GC) is one of the most common malignancies worldwide; unfortunately, the majority of GC patients is diagnosed at an advanced stage and die within 24 months after surgery because of recurrence and metastasis (1). The cure rate of gastric cancer is extremely low and the risk of treatment is large. It is well known that reactive oxygen species ROS levels are high in cancer cells compared to normal cells. ROS such as hydrogen peroxide, superoxide anions etc. are produced during mitochondria metabolism (2). Low levels of ROS can act as second messengers by participating in a variety of cellular physiological activities such as signal transduction, apoptosis, aging, proliferation and migration of cells. On the contrary, high levels of ROS have been recognized as driving factors in numerous diseases including cancer, aging, neurodegenerative disease, diabetes, cardiovascular disease, stroke, and asthma (3, 4), by inducing lipid, protein and DNA oxidation (5) thereby resulting in increased cellular apoptosis. On the other hand, there are cellular antioxidant mechanisms that clear excessive ROS (6, 7), such as superoxide dismutase (SOD), catalase (Cat), glutathione peroxidase (Gpx) and peroxiredoxin (Prxs). Prx V is a member of the Prxs family, which plays crucial roles in protecting cells from oxidative stress. Prxs are 1183 This article is freely accessible online.

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Section: Discussionmentioning

confidence: 99%

Peroxiredoxin V Inhibits Emodin-induced Gastric Cancer Cell Apoptosis via the ROS/Bcl2 Pathway

Jin

Sun

Liu

et al. 2019

In Vivo

View full text Add to dashboard Cite

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“…Antioxidants are known to mediate the key activities of cellular integrity maintenance and thus maintains the homeostasis of the host immune system. The genomic integrity of a cell is determined by the balance of pro-oxidants and the levels of antioxidants and an aberration in this balance can alter the normal cellular signaling cascades (Thyagarajan et al, 2018). Further, the alterations in the cellular signaling pathway can initiate the process of neocarcinogenesis (Monisha et al, 2017;Roy et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

An Investigation on the Therapeutic Potential of Butein, A Tretrahydroxychalcone Against Human Oral Squamous Cell Carcinoma

Bordoloi

Monisha

Roy

et al. 2019

Asian Pac J Cancer Prev

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Background: Oral squamous cell carcinoma (OSCC) is one of the most predominant cancers in India. With advances in the field of oncology, a number of therapies have emerged; however, they are minimally effective. Consequently, there is a need to develop safe and effective regimens for the treatment of OSCC. Butein, a tetrahydroxychalcone has been found to exhibit potent antioxidant, anti-inflammatory, and also anti-tumor effects against several cancer types. However, its effect on OSCC is not studied yet. Methods: The effect of butein on the viability, apoptosis, migration and invasion of OSCC cells was evaluated using MTT, colony formation, PI/FACS, live and dead, scratch wound healing, and matrigel invasion assays. Further Western blot analysis was done to evaluate the expression of different proteins involved in the regulation of cancer hallmarks. Results: This is the first report exemplifying the anti-cancer effect of butein against OSCC. Our results showed that butein exhibited potent anti-proliferative, cytotoxic, anti-migratory, and anti-invasive effects in OSCC cells. It suppressed the expression of NF-κB and NF-κB-regulated gene products such as COX-2, survivin and MMP-9 which are involved in the regulation of different processes like proliferation, survival, invasion, and metastasis of OSCC cells. Conclusion Collectively, these results suggest that butein has immense potential in the management of OSCC. Nonetheless, in vivo validation is critical before moving to clinical trials.

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“…The inhibition of GSH synthesis by a specific glutaminase (GLS) inhibitor and the simultaneous treatment with hydrogen peroxide resulted in a high apoptosis rate in ccRCC (58). Hence, additional administrationof antioxidants during (chemotherapeutic) cancer treatment have been frequently shown to have no or even pro-tumor effects (59,60). High GSH levels in RCC, which protect the tumor from increased ROS stress, should therefore be therapeutically exploited by reducing the antioxidant levels, of GSH, and increasing ROS stress at the same time to a level where healthy cells can still survive, but tumorous cells are forced into apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Papillary renal cell carcinomas rewire glutathione metabolism and are deficient in anabolic glucose synthesis

Alahmad

Paffrath

Clima

et al. 2019

Preprint

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Papillary renal cell carcinoma (pRCC) is a malignant kidney cancer with a prevalence of 7-20% of all renal tumors. Proteome and metabolome profiles of 19 pRCC and patient-matched healthy kidney controls were used to elucidate the regulation of metabolic pathways and the underlying molecular mechanisms. Glutathione (GSH), a main reactive oxygen species (ROS) scavenger, was highly increased and can be regarded as a new hallmark in this malignancy. Isotope tracing of pRCC derived cell lines revealed an increased de novo synthesis rate of GSH, based on glutamine consumption. Furthermore, rewiring of the main pathways involved in ATP and glucose synthesis was observed at the protein level. In contrast, transcripts encoding for the respiratory chain were not regulated, which prompts for non-genetic profiling. The molecular characteristics of pRCC are increased GSH synthesis to cope with ROS stress, deficient anabolic glucose synthesis, and compromised oxidative phosphorylation, which could potentially be exploited in innovative anti-cancer strategies.

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Potential Contributions of Antioxidants to Cancer Therapy: Immunomodulation and Radiosensitization

Cited by 115 publications

References 87 publications

Peroxiredoxin V Inhibits Emodin-induced Gastric Cancer Cell Apoptosis via the ROS/Bcl2 Pathway

Peroxiredoxin V Inhibits Emodin-induced Gastric Cancer Cell Apoptosis via the ROS/Bcl2 Pathway

An Investigation on the Therapeutic Potential of Butein, A Tretrahydroxychalcone Against Human Oral Squamous Cell Carcinoma

Papillary renal cell carcinomas rewire glutathione metabolism and are deficient in anabolic glucose synthesis

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