Interplay Between Mitochondrial Peroxiredoxins and ROS in Cancer Development and Progression

Ismail, Tayaba; Kim, Youni; Lee, Hongchan; Lee, Dong‐Seok; Lee, Hyun‐Shik

doi:10.3390/ijms20184407

Cited by 103 publications

(76 citation statements)

References 196 publications

(239 reference statements)

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“…Certain types of PRDX, such as PRDX5, relate to progression of carcinogenic tumors and are overexpressed in cases of endometrial and ovarian cancer. These associations are certainly linked to intense oxidative stress-related events that characterize cancer pathobiology 87 . As well known, oxidative stress is harmful to sperm's fertilizing capacity 88 and seminal plasma PRDX expression is one of the strategies for sperm protection, as discussed above.…”

Section: Discussionmentioning

confidence: 99%

Protein signatures of seminal plasma from bulls with contrasting frozen-thawed sperm viability

Gomes

Park

Viana

et al. 2020

Sci Rep

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The present study investigated the seminal plasma proteome of Holstein bulls with low (LF; n = 6) and high (HF; n = 8) sperm freezability. The percentage of viable frozen-thawed sperm (%ViableSperm) determined by flow cytometry varied from-2.2 in LF to + 7.8 in HF bulls, as compared to the average %ViableSperm (54.7%) measured in an 860-sire population. Seminal proteins were analyzed by label free mass spectrometry, with the support of statistical and bioinformatics analyses. this approach identified 1,445 proteins, associated with protein folding, cell-cell adhesion, NADH dehydrogenase activity, ATP-binding, proteasome complex, among other processes. There were 338 seminal proteins differentially expressed (p < 0.05) in LF and HF bulls. Based on multivariate analysis, BSP5 and seminal ribonuclease defined the HF phenotype, while spermadhesin-1, gelsolin, tubulins, glyceraldehyde-3-phosphate dehydrogenase, calmodulin, ATP synthase, sperm equatorial segment protein 1, peroxiredoxin-5, secretoglobin family 1D and glucose-6-phosphate isomerase characterized the LF phenotype. Regression models indicated that %ViableSperm of bulls was related to seminal plasma peroxiredoxin-5, spermadhesin-1 and the spermadhesin-1 × BSP5 interaction (R 2 = 0.84 and 0.79; p < 0.05). This report is the largest dataset of bovine seminal plasma proteins. Specific proteins of the non-cellular microenvironment of semen are potential markers of sperm cryotolerance. Sperm cryopreservation, artificial insemination (AI) and in vitro fertilization followed by embryo transfer are among the most used assisted reproductive technologies (ARTs), allowing genetic selection of farm animals 1 , conservation of wild and endangered species 2 , successful pregnancies for infertile couples 3 and preservation of fertility in cancer patients 4. Successful implementation of ARTs depends on cost-effective and efficient cryopreservation of sperm cells. Cryopreservation protocols include the dilution of fresh semen with extender containing cryoprotectants, buffers and antibiotics, followed by freezing in liquid nitrogen. Freezing and thawing semen interferes with the structure of the sperm membranes, alters functions of membrane proteins and ion channels, causes premature capacitation and acrosome reaction and yields excessive reactive oxygen species 5. Additionally, cryopreservation reduces both sperm metabolism and mitochondrial activity and alters sperm chromatin structure 6. All these effects result in lower motility and fertilizing capacity of frozen-thawed sperm when compared to untreated cells. Despite substantial improvements of protocols for cryopreservation of sperm and development of new extenders, it is currently accepted that 40 to 50% of sperm are incapable of proper fertilization after freezing and thawing 1. Studies indicate that certain males with nearly identical sperm parameters measured in fresh ejaculates present contrasting sperm viability after cryopreservation 7 and some bulls with high reproductive performance in natural mating have poor ...

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Section: Discussionmentioning

confidence: 99%

Protein signatures of seminal plasma from bulls with contrasting frozen-thawed sperm viability

Gomes

Park

Viana

et al. 2020

Sci Rep

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“…There are six subtypes of Prxs (Prx I-VI) found in mammals [147]. PRXs participate in the occurrence and development of tumors by regulating the level of redox inside and outside the mitochondria [148]. Prx1 was observed to be significantly increased in ESCC clinical tissue samples [149].…”

Section: Targeting the Prx Antioxidant System In Hncmentioning

confidence: 99%

ROS-Mediated Therapeutic Strategy in Chemo-/Radiotherapy of Head and Neck Cancer

Huang

Pan

2020

Oxidative Medicine and Cellular Longevity

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Head and neck cancer is a highly genetic and metabolic heterogeneous collection of malignancies of the lip, oral cavity, salivary glands, pharynx, esophagus, paranasal sinuses, and larynx with five-year survival rates ranging from 12% to 93%. Patients with head and neck cancer typically present with advanced stage III, IVa, or IVb disease and are treated with comprehensive modality including chemotherapy, radiotherapy, and surgery. Despite advancements in treatment modality and technique, noisome recurrence, invasiveness, and resistance as well as posttreatment complications severely influence survival rate and quality of life. Thus, new therapeutic strategies are urgently needed that offer enhanced efficacy with less toxicity. ROS in cancer cells plays a vital role in regulating cell death, DNA repair, stemness maintenance, metabolic reprogramming, and tumor microenvironment, all of which have been implicated in resistance to chemo-/radiotherapy of head and neck cancer. Adjusting ROS generation and elimination to reverse the resistance of cancer cells without impairing normal cells show great hope in improving the therapeutic efficacy of chemo-/radiotherapy of head and neck cancer. In the current review, we discuss the pivotal and targetable redox-regulating system including superoxide dismutases (SODs), tripeptide glutathione (GSH), thioredoxin (Trxs), peroxiredoxins (PRXs), nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/keap1), and mitochondria electron transporter chain (ETC) complexes and their roles in regulating ROS levels and their clinical significance implicated in chemo-/radiotherapy of head and neck cancer. We also summarize several old drugs (referred to as the non-anti-cancer drugs used in other diseases for a long time) and small molecular compounds as well as natural herbs which effectively modulate cellular ROS of head and neck cancer to synergize the efficacy of conventional chemo-/radiotherapy. Emerging interdisciplinary techniques including photodynamic, nanoparticle system, and Bio-Electro-Magnetic-Energy-Regulation (BEMER) therapy are promising measures to broaden the potency of ROS modulation for the benefit of chemo-/radiotherapy in head and neck cancer.

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“…Although the connection among reactive oxygen species (ROS) and cancer was suggested in the 1980s [1], in the last years, the scientific community has driven their attention to cellular oxidative stress for treating cancer [2][3][4]. ROS homeostasis is required for normal cell survival and proper cell 2 of 16 signaling, and the excessive production of ROS is considered as an important molecular hallmark for carcinogenesis [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Novel N,N′-Disubstituted Acylselenoureas as Potential Antioxidant and Cytotoxic Agents

et al. 2020

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Selenium compounds are pivotal in medicinal chemistry for their antitumoral and antioxidant properties. Forty seven acylselenoureas have been designed and synthesized following a fragment-based approach. Different scaffolds, including carbo- and hetero-cycles, along with mono- and bi-cyclic moieties, have been linked to the selenium containing skeleton. The dose- and time-dependent radical scavenging activity for all of the compounds were assessed using the in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assays. Some of them showed a greater radical scavenging capacity at low doses and shorter times than ascorbic acid. Therefore, four compounds were evaluated to test their protective effects against H2O2-induced oxidative stress. One derivative protected cells against H2O2-induced damage, increasing cell survival by up to 3.6-fold. Additionally, in vitro cytotoxic activity of all compounds was screened against several cancer cells. Eight compounds were selected to determine their half maximal inhibitory concentration (IC50) values towards breast and lung cancer cells, along with their selectivity indexes. The breast cancer cells turned out to be much more sensitive than the lung. Two compounds (5d and 10a) stood out with IC50 values between 4.2 μM and 8.0 μM towards MCF-7 and T47D cells, with selectivity indexes greater than 22.9. In addition, compound 10b exhibited dual antioxidant and cytotoxic activities. Although further evidence is needed, the acylselenourea scaffold could be a feasible frame to develop new dual agents.

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Interplay Between Mitochondrial Peroxiredoxins and ROS in Cancer Development and Progression

Cited by 103 publications

References 196 publications

Protein signatures of seminal plasma from bulls with contrasting frozen-thawed sperm viability

Protein signatures of seminal plasma from bulls with contrasting frozen-thawed sperm viability

ROS-Mediated Therapeutic Strategy in Chemo-/Radiotherapy of Head and Neck Cancer

Novel N,N′-Disubstituted Acylselenoureas as Potential Antioxidant and Cytotoxic Agents

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