Distinct Epigenetic Reprogramming, Mitochondrial Patterns, Cellular Morphology and Cytotoxicity after Bee Venom Treatment

2021 ◽  
Vol 16 ◽  
Author(s):  
Selcen Çelik Uzuner ◽  
Esra Birinci ◽  
Sinan Tetikoğlu ◽  
Ceren Birinci ◽  
Sevgi Kolaylı
Keyword(s):  
Mitochondrial Dna ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Bee Venom ◽  
Cellular Morphology ◽  
Epigenetic Therapy ◽  
Copy Numbers ◽  
Mitochondrial Dna Copy Number ◽  
Dna Copy Numbers ◽  
The Impact

Background: Bee venom is a promising agent for use in cancer treatment due to its selective cytotoxic potential for cancer cells through apoptotic pathways. However, there is no evidence for changes in epigenome and mitochondrial DNA copy numbers after bee venom application. The purpose of this study was to determine the impact of bee venom on cytosine modifications and mitochondrial DNA copy number variation. Methods: A broad range of methods was applied to elucidate the impact of bee venom on neoplastic cells. These included MTT assay for detection of cytotoxicity, immunostaining of cytosine modifications and mitochondria, assessment of cellular morphology by flow cytometry and quantification of mitochondrial DNA copy numbers using QPCR. Results: Bee venom-induced cell death was selective for cancer cells, where it triggered a response characterised by alteration of cytosine modification. In contrast, normal cells were more resistant to DNA modifications. Furthermore, application of the venom resulted in variation of mitochondrial membrane permeability and mitochondrial DNA copy numbers, together with alterations in cell morphology manifesting as a reduced affected cell size. Conclusion: The study findings suggest that bee venom can be used as a selective DNA (de)methylating agent in cancer. Various agents (such as Decitabine and 5-azacytidine) have been synthesized and developed for use in cancer treatment, and a range of syntheses, and preparation and application methods have been described for these patented drugs. However, to the best of our knowledge, no previous research has investigated the use of bee venom or any component thereof for epigenetic therapy in cancer cells.

scholarly journals Sperm mitochondrial DNA copy numbers in normal and abnormal semen analysis: a systematic review and meta-analysis.

2021 ◽  
Author(s):  
Daria Popova ◽  
Priya Bhide ◽  
Francesco DAntonio ◽  
Purusotam Basnet ◽  
Ganesh Acharya
Keyword(s):  
Mitochondrial Dna ◽  
Sperm Motility ◽  
Semen Quality ◽  
Semen Analysis ◽  
Meta Analysis ◽  
Semen Parameters ◽  
Spermatozoa Motility ◽  
Standard Methodology ◽  
Copy Numbers ◽  
Dna Copy Numbers

Background: Normal mature sperm have a considerably reduced number of mitochondria which provide the energy required for progressive sperm motility. Literature suggests that disorders of sperm motility may be linked to abnormal sperm mitochondrial number and function. Objectives: To summarise the evidence from literature regarding the association of mitochondrial DNA copy numbers and semen quality with a particular emphasis on the spermatozoa motility. Search strategy: Standard methodology recommended by Cochrane. Selection criteria: All published primary research reporting on differences in mitochondrial DNA copy numbers between the sperm of males with a normal and abnormal semen analysis. Data collection and analysis: Using standard methodology recommended by Cochrane we pooled results using a random effects model and the findings were reported as a standardised mean difference. Main results: We included 10 trials. The primary outcome was sperm mitochondrial DNA copy numbers. A meta-analysis including five studies showed significantly higher mitochondrial DNA copy numbers in abnormal semen analysis as compared to normal semen analysis(SMD 1.08, 95% CI 0.74-1.43). Three other studies not included in the meta-analysis showed a significant negative correlation between mitochondrial DNA copy numbers and semen parameters. The quality of evidence was assessed as good to very good in 60% of studies. Conclusions: Our review demonstrates significantly higher mitochondrial DNA in human sperm cells of men with abnormal semen analysis in comparison to men with normal semen analysis. PROSPERO registration: CRD42019118841 Funding None received

scholarly journals Effect of bariatric surgery on circulating and urinary mitochondrial DNA copy numbers in obesity with or without diabetes

2020 ◽  
Vol 8 (1) ◽  
pp. e001372
Author(s):  
Mihae Seo ◽  
Hyoungnae Kim ◽  
Hyunjin Noh ◽  
Jin Seok Jeon ◽  
Dong Won Byun ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Mitochondrial Dna ◽  
Mitochondrial Dysfunction ◽  
Control Group ◽  
Copy Numbers ◽  
Patient Groups ◽  
Dna Copy Numbers ◽  
Nicotinamide Adenine Dinucleotide Dehydrogenase ◽  
Design And Methods ◽  
Obesity Patient

IntroductionRecent studies have suggested that extracellular circulating and urinary mitochondrial DNA (mtDNA) are associated with mitochondrial dysfunction in obesity and type 2 diabetes mellitus (T2DM). However, the changes to cell-free serum and urinary mtDNA after bariatric surgery in patients with obesity with T2DM have not been investigated to date.Research design and methodsWe prospectively recruited patients with obesity (n=18), and with obesity and T2DM (n=14) who underwent bariatric surgery, along with healthy volunteers (HV) as a control group (n=22). Serum and urinary mitochondrial nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND-1) and cytochrome-c oxidase 3 (mtCOX-3) copy numbers were measured using quantitative PCR (qPCR). The mtDNA copy numbers of patients with obesity (with and without T2DM) were followed up 6 months after surgery.ResultsThe copy numbers of urinary mtND-1 and mtCOX-3 in patients with obesity, with or without T2DM, were higher than those in the HVs. Moreover, urinary mtCOX-3 copy number increased in patients with obesity with T2DM compared with patients with obesity without T2DM (p=0.018). Meanwhile, serum mtCOX-3 copy numbers in HV were higher in both obesity patient groups (p=0.040). Bariatric surgery reduced urinary mtND-1 and mtCOX-3 copy numbers, as well as serum mtCOX-3 copy numbers only in patients with obesity with T2DM.ConclusionThese results suggest that T2DM induces greater kidney mitochondrial dysfunction in patients with obesity, which can be effectively restored with bariatric surgery.

Variations in Mitochondrial DNA Copy Numbers in MS Brains

2008 ◽  
Vol 35 (3) ◽  
pp. 283-287 ◽  
Author(s):  
Andrei Blokhin ◽  
Tamara Vyshkina ◽  
Samuel Komoly ◽  
Bernadette Kalman
Keyword(s):  
Mitochondrial Dna ◽  
Copy Numbers ◽  
Dna Copy Numbers

Effects of Micronucleus Frequencies and Mitochondrial DNA Copy Numbers among Benzene‐Exposed Workers in China

2020 ◽  
Vol 61 (3) ◽  
pp. 355-360 ◽  
Author(s):  
Anqi Li ◽  
Yuan Sun ◽  
Tongshuai Wang ◽  
Kan Wang ◽  
Tuanwei Wang ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Copy Numbers ◽  
Exposed Workers ◽  
Dna Copy Numbers

scholarly journals Deep sequencing shows that accumulation of potentially pathogenic mtDNA mutations rather than mtDNA copy numbers may be associated with early embryonic loss

2020 ◽  
Vol 37 (9) ◽  
pp. 2181-2188
Author(s):  
Licheng Ji ◽  
Tingting Liao ◽  
Juan Yang ◽  
Houming Su ◽  
Jianyuan Song ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Spontaneous Abortion ◽  
Missense Mutations ◽  
Mtdna Copy Number ◽  
Mtdna Mutations ◽  
Pathogenic Mutations ◽  
Copy Numbers ◽  
Significant Difference ◽  
Embryonic Loss ◽  
Dna Copy Numbers

Abstract Purpose To explore the relationship between mitochondrial DNA quantity and heteroplasmy and early embryonic loss. Methods A total of 150 villous samples from patients with spontaneous abortion (SA, n = 75) or induced abortion (IA, n = 75) were collected. qPCR and next-generation sequencing (NGS) were used to test mitochondrial DNA quantity and heteroplasmy. Missense mutations with a CADD score > 15 and heteroplasmy ≥ 70% were defined as potentially pathogenic mutations. Results With respect to mitochondrial DNA copy numbers, there was no significant difference between the SA and IA groups (median (IQR), 566 (397–791) vs. 614 (457–739); P = 0.768) or between the euploid and aneuploid groups (median (IQR), 516 (345–730) vs. 599 (423–839); P = 0.107). mtDNA copy numbers were not associated with spontaneous abortion using logistic regression analysis (P = 0.196, 95% CI 1.000–1.001). In addition, more patients harbored possibly pathogenic mtDNA mutations in their chorionic villi in the SA group (70.7%, 53/75) compared with the IA group (54.7%, 41/75; P < 0.05). However, there was no statistical difference between the euploid (80%, 24/30) and aneuploid groups (64.4%, 29/45; p = 0.147). Conclusion Early embryonic loss and the formation of aneuploidy were not related to mtDNA copy number. Patients with spontaneous abortion were more likely to have possibly pathogenic mutations in their mtDNA, and this may assist in purifying pathogenic mtDNA. However, whether the accumulation of these potentially morbific mtDNA mutations caused early embryonic loss requires further investigation.

scholarly journals Pomegranate Extract (POMx) Induces Mitochondrial Dysfunction and Apoptosis of Oral Cancer Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1117
Author(s):  
Sheng-Yao Peng ◽  
Li-Ching Lin ◽  
Shu-Rong Chen ◽  
Ammad A. Farooqi ◽  
Yuan-Bin Cheng ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mitochondrial Dna ◽  
Oral Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Atp Depletion ◽  
Mitochondrial Dna Copy Number ◽  
Polyphenolic Extract ◽  
Oral Cancer Cells ◽  
Gene Mrna

The anticancer effect of pomegranate polyphenolic extract POMx in oral cancer cells has rarely been explored, especially where its impact on mitochondrial functioning is concerned. Here, we attempt to evaluate the proliferation modulating function and mechanism of POMx against human oral cancer (Ca9-22, HSC-3, and OC-2) cells. POMx induced ATP depletion, subG1 accumulation, and annexin V/Western blotting-detected apoptosis in these three oral cancer cell lines but showed no toxicity to normal oral cell lines (HGF-1). POMx triggered mitochondrial membrane potential (MitoMP) disruption and mitochondrial superoxide (MitoSOX) generation associated with the differential downregulation of several antioxidant gene mRNA/protein expressions in oral cancer cells. POMx downregulated mitochondrial mass, mitochondrial DNA copy number, and mitochondrial biogenesis gene mRNA/protein expression in oral cancer cells. Moreover, POMx induced both PCR-based mitochondrial DNA damage and γH2AX-detected nuclear DNA damage in oral cancer cells. In conclusion, POMx provides antiproliferation and apoptosis of oral cancer cells through mechanisms of mitochondrial impairment.

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