Insights into the Role of Oxidative Stress in Ovarian Cancer

Ding, Dan-Ni; Xie, Liangzhen; Shen, Ying; Li, Jia; Guo, Ying; Fu, Yaoyao; Liu, Fang-Yuan; Han, Feng-Juan

doi:10.1155/2021/8388258

Cited by 27 publications

(25 citation statements)

References 244 publications

(308 reference statements)

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“…Studies have shown that when detached cancer cells are treated with platinum chemotherapy, they experience a stress state and surge of ROS formation [29]. However, the strong redox regulation ability of cancer cells ensures that cancer cells can withstand harsh conditions to survive [30]. Ferroptosis is a form of RCD caused by uncontrolled redox homeostasis.…”

Section: Discussionmentioning

confidence: 99%

ACSL1-induced ferroptosis and platinum resistance in ovarian cancer by increasing FSP1 N-myristylation and stability

Zhang

Deng

et al. 2023

Cell Death Discov.

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Reprogramming of lipid metabolism, which modulates energy utilization and cell signaling, maintains cell survival and promotes cancer metastasis in cancer cells. Ferroptosis is a type of cell necrosis caused by an overload of lipid oxidation, which has been demonstrated to be involved in cancer cell metastasis. However, the mechanism by which fatty acid metabolism regulates the anti-ferroptosis signaling pathways is not fully understood. The formation of ovarian cancer spheroids helps to counteract the hostile microenvironment of the peritoneal cavity with low oxygen, shortage of nutrients, and subjected to platinum therapy. Previously, we demonstrated that Acyl-CoA synthetase long-chain family member 1 (ACSL1) promotes cell survival and peritoneal metastases in ovarian cancer, but the mechanism is still not well elucidated. In this study, we demonstrate that the formation of spheroids and under exposure to platinum chemotherapy increased the levels of anti-ferroptosis proteins as well as ACSL1. Inhibition of ferroptosis can enhance spheroid formation and vice versa. Genetic manipulation of ACSL1 expression showed that ACSL1 reduced the level of lipid oxidation and increased the resistance to cell ferroptosis. Mechanistically, ACSL1 increased the N-myristoylation of ferroptosis suppressor 1 (FSP1), resulting in the inhibition of its degradation and translocation to the cell membrane. The increase in myristoylated FSP1 functionally counteracted oxidative stress-induced cell ferroptosis. Clinical data also suggested that ACSL1 protein was positively correlated with FSP1 and negatively correlated with the ferroptosis markers 4-HNE and PTGS2. In conclusion, this study demonstrated that ACSL1 enhances antioxidant capacity and increases ferroptosis resistance by modulating the myristoylation of FSP1.

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Section: Discussionmentioning

confidence: 99%

ACSL1-induced ferroptosis and platinum resistance in ovarian cancer by increasing FSP1 N-myristylation and stability

Zhang

Deng

et al. 2023

Cell Death Discov.

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“…Oxidative stress tolerance is a significant factor in ovarian carcinogenesis at several stages of the disease, including its onset, development, invasion, and metastasis [ 89 ]. Moreover, oxidative stress control has been considered one of the noteworthy therapeutic targets in OC.…”

Section: Phenolic Acids Involved In the Regulation Of Molecular Targetsmentioning

confidence: 99%

“…PCA also showed inhibition of cancer cell proliferation and apoptosis induction via reduced Bcl-2 expression, increased Bax level, activated JNK/p38 MAPK and Fas/FasL pathways, and had an inhibitory effect on genes associated with inflammation [ 84 , 87 , 88 ]. Oxidative stress control is one of the striking therapeutic targets in OC [ 89 ]. Hence, the antioxidant effect by PCA indicates its therapeutic efficacy against OC, and multiple clinical trials are already registered to evaluate its effectiveness in ovarian cancer [ 90 , 91 ].…”

Section: Summary and Future Perspectivesmentioning

confidence: 99%

Phenolic Acids-Mediated Regulation of Molecular Targets in Ovarian Cancer: Current Understanding and Future Perspectives

et al. 2023

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Cancer is a global health concern with a dynamic rise in occurrence and one of the leading causes of mortality worldwide. Among different types of cancer, ovarian cancer (OC) is the seventh most diagnosed malignant tumor, while among the gynecological malignancies, it ranks third after cervical and uterine cancer and sadly bears the highest mortality and worst prognosis. First-line treatments have included a variety of cytotoxic and synthetic chemotherapeutic medicines, but they have not been particularly effective in extending OC patients’ lives and are associated with side effects, recurrence risk, and drug resistance. Hence, a shift from synthetic to phytochemical-based agents is gaining popularity, and researchers are looking into alternative, cost-effective, and safer chemotherapeutic strategies. Lately, studies on the effectiveness of phenolic acids in ovarian cancer have sparked the scientific community’s interest because of their high bioavailability, safety profile, lesser side effects, and cost-effectiveness. Yet this is a road less explored and critically analyzed and lacks the credibility of the novel findings. Phenolic acids are a significant class of phytochemicals usually considered in the nonflavonoid category. The current review focused on the anticancer potential of phenolic acids with a special emphasis on chemoprevention and treatment of OC. We tried to summarize results from experimental, epidemiological, and clinical studies unraveling the benefits of various phenolic acids (hydroxybenzoic acid and hydroxycinnamic acid) in chemoprevention and as anticancer agents of clinical significance.

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“…This condition leads to destructive biochemical processes for the cell and is one of the causes of many diseases. Currently, overproduction of ROS is associated with oncological [ 57 , 58 ], mental [ 59 , 60 ], neurodegenerative [ 61 ], and cardiovascular diseases [ 62 ], type 2 diabetes mellitus [ 63 ], chronic obstructive pulmonary disease [ 64 ], autoimmune diseases [ 65 , 66 ], the aging process [ 67 ], osteoporosis [ 68 ], asthma [ 69 ], and gastrointestinal disorders [ 70 ].…”

Section: Reactive Oxygen and Nitrogen Species (Rons) Formation And Ox...mentioning

confidence: 99%

Essential Protective Role of Catalytically Active Antibodies (Abzymes) with Redox Antioxidant Functions in Animals and Humans

Tolmacheva

Nevinsky

2022

IJMS

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During the life of aerobic organisms, the oxygen resulting from numerous reactions is converted into reactive oxygen species (ROS). Many ROS are dangerous due to their high reactivity; they are strong oxidants, and react with various cell components, leading to their damage. To protect against ROS overproduction, enzymatic and non-enzymatic systems are evolved in aerobic cells. Several known non-enzymatic antioxidants have a relatively low specific antioxidant activity. Superoxide dismutases, catalase, glutathione peroxidase, glutathione S-transferase, thioredoxin, and the peroxiredoxin families are the most important enzyme antioxidants. Artificial antibodies catalyzing redox reactions using different approaches have been created. During the past several decades, it has been shown that the blood and various biological fluids of humans and animals contain natural antibodies that catalyze different redox reactions, such as classical enzymes. This review, for the first time, summarizes data on existing non-enzymatic antioxidants, canonical enzymes, and artificial or natural antibodies (abzymes) with redox functions. Comparing abzymes with superoxide dismutase, catalase, peroxide-dependent peroxidase, and H2O2-independent oxidoreductase activities with the same activities as classical enzymes was carried out. The features of abzymes with the redox activities are described, including their exceptional diversity in the optimal pH values, dependency and independence on various metal ions, and the reaction rate constants for healthy donors and patients with different autoimmune diseases. The entire body of evidence indicates that abzymes with redox antioxidant activities existing in the blood for a long time compared to enzymes are an essential part of the protection system of humans and animals from oxidative stress.

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Insights into the Role of Oxidative Stress in Ovarian Cancer

Cited by 27 publications

References 244 publications

ACSL1-induced ferroptosis and platinum resistance in ovarian cancer by increasing FSP1 N-myristylation and stability

ACSL1-induced ferroptosis and platinum resistance in ovarian cancer by increasing FSP1 N-myristylation and stability

Phenolic Acids-Mediated Regulation of Molecular Targets in Ovarian Cancer: Current Understanding and Future Perspectives

Essential Protective Role of Catalytically Active Antibodies (Abzymes) with Redox Antioxidant Functions in Animals and Humans

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