ubiquinone and Lung-Neoplasms

Pancreatic adenocarcinoma (PDAC) and lung cancer are expected to represent the most common cancer types worldwide until 2030. Under typical conditions, mitochondria provide the bulk of the energy needed to sustain cell life. For that inhibition of mitochondrial complex ΙΙ (CΙΙ) and ubiquinone oxidoreductase with natural treatments may represent a promising cancer treatment option. A naturally occurring flavonoid with biological anti-cancer effects is chyrsin. Due to their improved bioavailability, penetrative power, and efficacy, chitosan-chrysin nano-formulations (CCNPs) are being used in medicine with increasing frequency. Chitosan (cs) is also regarded as a highly versatile and adaptable polymer. The cationic properties of Cs, together with its biodegradability, high adsorption capacity, biocompatibility, effect on permeability, ability to form films, and adhesive properties, are advantages. In addition, Cs is thought to be both safe and economical. CCNPs may indeed be therapeutic candidates in the treatment of pancreatic adenocarcinoma (PDAC) and lung cancer by blocking succinate ubiquinone oxidoreductase.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Chitosan; Flavonoids; Humans; Lung Neoplasms; Nanoparticles; Pancreatic Neoplasms; Succinate Dehydrogenase; Ubiquinone

Antrodia camphorata is an expensive mushroom that grows on the inner cavity of an endangered native tree of Taiwan namely Cinnamomum kanehirai Hayata. It is used as a traditional medicine in Taiwan and has several health benefits including free radical scavenging, anti-inflammatory, antimicrobial, hepatoprotective, neuroprotective, antidiabetic, and free radical-induced DNA damage protecting activities. Antroquinonol is a tetrahydro ubiquinone derivative found predominately in the mycelium of Antrodia camphorata, and is characterized by numerous biological and pharmacological activities. Several studies have revealed potential anticancer effects of antroquinonol in various carcinogenic models. Moreover, a phase II clinical trial is ongoing in the US and Taiwan to treat the lung cancer patients with this active compound. The present review aims at depicting a detailed view of the synthetic procedures of antroquinonol as well as deciphering its potential health benefits with a special emphasis on anticancer properties.

Topics: Animals; Antineoplastic Agents, Phytogenic; Antrodia; Cell Proliferation; DNA Damage; Humans; Lung Neoplasms; Ubiquinone

Targeting ferroptosis, a unique cell death modality triggered by unrestricted lipid peroxidation, in cancer therapy is hindered by our incomplete understanding of ferroptosis mechanisms under specific cancer genetic contexts. KEAP1 (kelch-like ECH associated protein 1) is frequently mutated or inactivated in lung cancers, and KEAP1 mutant lung cancers are refractory to most therapies, including radiotherapy. In this study, we identify ferroptosis suppressor protein 1 (FSP1, also known as AIFM2) as a transcriptional target of nuclear factor erythroid 2-related factor 2 (NRF2) and reveal that the ubiquinone (CoQ)-FSP1 axis mediates ferroptosis- and radiation- resistance in KEAP1 deficient lung cancer cells. We further show that pharmacological inhibition of the CoQ-FSP1 axis sensitizes KEAP1 deficient lung cancer cells or patient-derived xenograft tumors to radiation through inducing ferroptosis. Together, our study identifies CoQ-FSP1 as a key downstream effector of KEAP1-NRF2 pathway and as a potential therapeutic target for treating KEAP1 mutant lung cancers.

Topics: Apoptosis Regulatory Proteins; Ferroptosis; Humans; Kelch-Like ECH-Associated Protein 1; Lipid Peroxidation; Lung Neoplasms; Mitochondrial Proteins; NF-E2-Related Factor 2; Ubiquinone

Coenzyme Q10 (CoQ10) is a ubiquitous molecule in living organisms serving as a cofactor in energy production. Epidemiological studies have reported low CoQ10 levels being associated with an increased risk of various cancers. We conducted the first study to evaluate the association of CoQ10 concentrations with lung cancer risk.. A nested case-control study including 201 lung cancer cases and 395 matched controls from the Southern Community Cohort Study was conducted. Plasma CoQ10 levels were measured using high-performance liquid chromatography with photo-diode array detection. Conditional logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between plasma CoQ10 levels and lung cancer risk.. Plasma CoQ10 concentration was inversely associated with the risk of lung cancer. After adjusting for age, sex, race, and socioeconomic status, the OR (95% CI) comparing the third to first tertile was 0.57 (0.36-0.91, P for trend = 0.02). Further adjustments for smoking, alcohol, chronic obstructive pulmonary disease, and body mass index attenuated the point estimate slightly (OR = 0.60, 95% CI = 0.34-1.08, P for trend = 0.11), comparing third to first tertiles. Stratified analyses identified a significant inverse association between plasma CoQ10 levels and lung cancer risk in current smokers, but not in former/never smokers. The association was more evident in cases who were diagnosed within 1 year of blood draw than in cases diagnosed after 1 year.. Low plasma CoQ10 was significantly associated with increased lung cancer risk, particularly among current smokers. The stronger association seen shortly following the blood draw suggests that CoQ10 may be related to disease progression.

Topics: Biomarkers, Tumor; Case-Control Studies; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Poverty; Prognosis; Prospective Studies; Risk Factors; Southeastern United States; Ubiquinone; Vitamins

Lung and breast cancer are the leading causes of mortality in women worldwide. The discovery of molecular alterations that underlie these two cancers and corresponding drugs has contributed to precision medicine. We found that CCND2 is a common target in lung and breast cancer. Hypermethylation of the

Topics: Antineoplastic Agents; Biomarkers, Tumor; Breast Neoplasms; Cell Movement; Cell Proliferation; Cyclin D2; DNA Methylation; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Prognosis; Promoter Regions, Genetic; Proportional Hazards Models; RNA, Messenger; Ubiquinone

Amitriptyline, a tricyclic antidepressant, has been proposed as an antitumoral drug in oxidative therapy. Its pro-apoptotic effects, mediated by high reactive oxygen species generation, have been already described. In this study we analysed the effect of amitriptyline on the biosynthesis of coenzyme Q

Topics: Amitriptyline; Cell Line, Tumor; Dose-Response Relationship, Drug; Humans; Kinetics; Lung Neoplasms; Reactive Oxygen Species; Ubiquinone

Oxidative damage is a major contributing factor to carcinogenesis and obstructive disorders in lungs. Current evidence suggests that the inflammatory processes yield to oxidative mechanisms, which underlie COPD, lung cancer, and obstructive sleep apnea syndrome (OSAS). This study aimed to evaluate the oxidative damage in these diseases by evaluating the oxidative and antioxidant biomarkers.. Malondialdehyde, 8-oxo-7,8-dihydro-2'-deoxyguanosine, and coenzyme Q10 levels were evaluated in the blood samples of subjects with COPD, lung cancer, and OSAS by high-pressure liquid chromatography.. A total of 111 participants (35 females, 76 males) with OSAS (n = 29), COPD (n = 26), and lung cancer (n = 28) and healthy controls (n = 28) were included in the study. The malondialdehyde and coenzyme Q10 levels were significantly higher in all 3 diseases when compared with controls (P < .01), whereas 8-oxo-7,8-dihydro-2'-deoxyguanosine levels were only significantly higher than in healthy controls in subjects with lung cancer (P = .005). The highest levels of malondialdehyde and coenzyme Q10 were determined in subjects with OSAS and lung cancer, respectively. The highest 8-oxo-7,8-dihydro-2'-deoxyguanosine levels were also observed in subjects with lung cancer, but the differences of this biomarker with other diagnoses were not statistically significant (P = .56).. Oxidative damage was observed in all 3 diagnoses, and, as a response to oxidative stress, antioxidant mechanisms were also active in these diseases. Malondialdehyde and 8-oxo-7,8-dihydro-2'-deoxyguanosine were found to be efficiently usable in the evaluation of oxidative damage in chronic respiratory diseases. (ClinicalTrials.gov registration NCT02406053.).

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Antioxidants; Biomarkers; Case-Control Studies; Deoxyguanosine; Female; Humans; Lung Neoplasms; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Sleep Apnea, Obstructive; Ubiquinone

Mitochondrial dysregulation is closely associated with excessive reactive oxygen species (ROS) production. Altered redox homeostasis has been implicated in the onset of several diseases including cancer. Mitochondrial DNA (mtDNA) and proteins are particularly sensitive to ROS as they are in close proximity to the respiratory chain (RC). Mitoquinone (MitoQ), a mitochondria-targeted redox agent, selectively damages breast cancer cells possibly through damage induced via enhanced ROS production. However, the effects of MitoQ and other triphenylphosphonium (TPP+) conjugated agents on cancer mitochondrial homeostasis remain unknown. The primary objective of this study was to determine the impact of mitochondria-targeted agent [(MTAs) conjugated to TPP+: mitoTEMPOL, mitoquinone and mitochromanol-acetate] on mitochondrial physiology and mtDNA integrity in breast (MDA-MB-231) and lung (H23) cancer cells. The integrity of the mtDNA was assessed by quantifying the degree of mtDNA fragmentation and copy number, as well as by measuring mitochondrial proteins essential to mtDNA stability and maintenance (TFAM, SSBP1, TWINKLE, POLG and POLRMT). Mitochondrial status was evaluated by measuring superoxide production, mitochondrial membrane depolarization, oxygen consumption, extracellular acidification and mRNA or protein levels of the RC complexes along with TCA cycle activity. In this study, we demonstrated that all investigated MTAs impair mitochondrial health and decrease mtDNA integrity in MDA-MB-231 and H23 cells. However, differences in the degree of mitochondrial damage and mtDNA degradation suggest unique properties among each MTA that may be cell line, dose and time dependent. Collectively, our study indicates the potential for TPP+ conjugated molecules to impair breast and lung cancer cells by targeting mitochondrial homeostasis.

Topics: Breast Neoplasms; DNA, Mitochondrial; Female; Humans; Lung Neoplasms; Mitochondria; Mitochondrial Membranes; Mitochondrial Proteins; Organophosphorus Compounds; Oxidation-Reduction; Oxidative Stress; Small Cell Lung Carcinoma; Superoxides; Ubiquinone

Antroquinonol a derivative of Antrodia camphorata has been reported to have antitumor effects against various cancer cells. However, the effect of antroquinonol on cell signalling and survival pathways in non-small cell lung cancer (NSCLC) cells has not been fully demarcated. Here we report that antroquinonol treatment significantly reduced the proliferation of three NSCLC cells. Treatment of A549 cells with antroquinonol increased cell shrinkage, apoptotic vacuoles, pore formation, TUNEL positive cells and increased Sub-G1 cell population with respect to time and dose dependent manner. Antroquinonol treatment not only increased the Sub-G1 accumulation but also reduced the protein levels of cdc2 without altering the expression of cyclin B1, cdc25C, pcdc2, and pcdc25C. Antroquinonol induced apoptosis was associated with disrupted mitochondrial membrane potential and activation of Caspase 3 and PARP cleavage in A549 cells. Moreover, antroquinonol treatment down regulated the expression of Bcl2 proteins, which was correlated with the decreased PI3K and mTOR protein levels without altering pro apoptotic and anti apoptotic proteins. Results from the microarray analysis demonstrated that antroquinonol altered the expression level of miRNAs compared with untreated control in A549 cells. The data collectively suggested the antiproliferative effect of antroquinonol on NSCLC A549 cells, which provides useful information for understanding the anticancer mechanism influenced by antroquinonol and is the first report to suggest that antroquinonol may be a promising chemotherapeutic agent for lung cancer.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Membrane Potentials; MicroRNAs; Phosphatidylinositol 3-Kinases; Signal Transduction; TOR Serine-Threonine Kinases; Ubiquinone

Early diagnosis and prevention is very important for lung cancer patients. Previous studies have emphasized that the level of coenzyme Q10 (CoQ10), present primarily in mitochondria, decreases with age and is low in patients with chronic diseases. Our goal was to find out if there is any relationship between lung cancer and CoQ10 and lipid peroxidation levels.. Blood samples from lung cancer patients were collected. Total and oxide CoQ10 levels, 8-OHdG (product of DNA damage), and malondialdehyde (MDA) levels (lipid peroxidation) were analyzed with high performance liquid chromatography (HPLC).. The MDA level (P<0.001) and DNA damage rate (8-OHdG) (P<0.001) was higher in cancer patients than in the control group; in contrast, theCoQ10 enzyme level was significantly lower (P<0.001).. The results suggest that the aforementioned parameters can be useful for lung cancer risk assessment.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers, Tumor; Case-Control Studies; Deoxyguanosine; DNA Damage; Humans; Lipid Peroxidation; Lung Neoplasms; Malondialdehyde; Mitochondria; Oxidative Stress; Risk Assessment; Ubiquinone

The effect of oral ubiquinone (Q10) intake on the in vivo response of tumors to single dose radiotherapy was examined. The human small-cell lung cancer (SCLC) line CPH 054A, which is sensitive to relatively low doses of X-radiation, was grown as subcutaneous transplants in the flanks of nude nu/nu mice. When macroscopical growth was established, groups of mice received either 10, 20 or 40 mg/kg Q10 in 30 mL soy oil intragastrically daily on 4 consecutive days. Controls received either 30 mL of pure soy oil or nothing. Three h after the last dose half of the tumors in each group received a single radiation dose of 5 Gy, using a 300 kV therapeutic unit. The macroscopic growth pre- and posttreatment was analyzed according to a transformed Gompertz algorithm using the software program GROWTH. Treatment with Q10 or soy oil alone had no effect on tumor growth compared with untreated controls. Groups of tumors that received Q10 and radiotherapy had a significantly lower specific growth delay (SGD) than the radiotherapy-only groups. This effect was significant at 40 mg/kg and borderline at 20 mg/kg, whereas at 10 mg/kg no radioprotection was seen. We conclude that systemic Q10 reduces the response to single dose tumor irradiation inxenotransplanted human SCLC tumors.

Topics: Animals; Carcinoma, Small Cell; Humans; Lung Neoplasms; Mice; Mice, Nude; Neoplasm Transplantation; Transplantation, Heterologous; Tumor Cells, Cultured; Ubiquinone

Platelet aggregation, plasma beta-thromboglobulin (beta-TG) concentration and coenzyme Q10 content in serum and platelets were measured in 45 patients with unresectable carcinoma of the lung and in 7 patients with metastatic pulmonary tumor before and after receiving chemotherapy. A significant increase in the plasma beta-TG concentration in cancer patients (47.4 +/- 18.7 ng/ml) was observed (p less than 0.001) compared to the controls (30.3 +/- 9.2 ng/ml). Serum coenzyme Q10 content was lower in cancer patients (0.42 +/- 0.19 micrograms/ml) (p less than 0.05) compared to the controls (0.57 +/- 0.24 micrograms/ml). The reason of decrease in serum coenzyme Q10 content in cancer patients was difficult to explain. No significant difference of the coenzyme Q10 content in platelets (1 X 10(8) cells) was observed either cancer patients (12.5 +/- 2.8 ng) or the controls (12.6 +/- 2.1 ng). No significant correlation was noted among platelet aggregation, plasma beta-TG concentration and coenzyme Q10 content in serum and platelets. Administration of either vindesine or KW2083 did not influence the coenzyme Q10 content in platelets. These results suggest that ATP synthetic pathway by oxidative phosphorylation in platelet be maintained in cancer patients, although a significant increase of plasma beta-TG concentration appears to be associated with an acceleration in the metabolic turnover of platelet.

Topics: Adult; Aged; beta-Thromboglobulin; Blood Platelets; Chromatography, High Pressure Liquid; Coenzymes; Collagen; Epinephrine; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Platelet Aggregation; Platelet Count; Ubiquinone; Vinblastine; Vindesine

Cardiotoxicity induced by adriamycin and protective effect by coenzyme Q10 were studied in 80 closely-followed patients receiving chemotherapy with adriamycin. Serial electrocardiograms were recorded immediately before and after the administration of adriamycin each times. The electrocardiographic parameters (heart rate, P-Q duration, QRS-duration, QRS voltage and QTc-duration) were analyzed. In patients treated with adriamycin alone, QTc-duration was prolonged significantly. On the other hand, in patients treated with adriamycin plus coenzyme Q10, QTc-duration was not significantly prolonged. This Suggests that coenzyme Q10 may reduce negative inotropic action induced by adriamycin. Further, the QRS voltage was also significantly decreased in patients treated with adriamycin alone, but was not decreased in patients treated with adriamycin plus coenzyme Q10. These findings suggest that some electrocardiographic changes due to adriamycin may be prevented by coenzyme Q10.

Topics: Coenzymes; Doxorubicin; Electrocardiography; Female; Gastrointestinal Neoplasms; Heart; Heart Rate; Humans; Leukemia; Lung Neoplasms; Lymphoma; Male; Middle Aged; Neoplasms; Time Factors; Ubiquinone

An unique combination treatment for cancer patients has been attempted in our department. The treatment consists of 500 rad irradiation of cobalt 60 on the first day and drip infusion of mixture of 50mg adriamycin, 500mg cyclophosphamide and 500mg 5-fluorouracil on the next day. This combination therapy was repeated every 3 weeks. The myocardial intoxication may be a great problem in this therapy. Investigation was performed in 40 cancer patients in order to clarify of Coenzyme Q10 (CoQ10) could show any protecting effect upon the possible myocardial intoxication. All patients were divided into 2 groups; one with CoQ10 of 20 patients, who received CoQ10 of 90mg/day orally and the other without CoQ10 of 20 patients. In the group without CoQ10, cardiothoracic ratio (CTR) and pulse rate increased significantly in all patients and on ECG low voltage of QRS complex was seen in 2 cases, changes of ST-segment, T-wave and appearance of arrhythmia were more than frequent in the group without CoQ10 than that with CoQ10. It is concluded that CoQ10 is effective for protecting the myocardium in this cancer therapy.

Topics: Adult; Aged; Breast Neoplasms; Coenzymes; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Electrocardiography; Female; Fluorouracil; Heart; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Thyroid Neoplasms; Ubiquinone

Pretreatment for four days with coenzyme Q10 (CoQ10) significantly lowered the acute toxicity in female C3H/HeNCrlBR mice given moderately lethal (15.0 and 20.0 mg/kg) i.p. doses of adriamycin as well as in male ICR/Hla mice given 12.5 mg/kg i.p. adriamycin. In both strains of mice, CoQ10 pretreatment did not protect the mice at higher i.p. adriamycin dose levels. When adriamycin was administered by the clinically-used i.v. route, CoQ10 pretreatment did not reduce acute toxicity at moderately lethal doses in either strain. At higher i.v. adriamycin dose levels, CoQ10 pretreatment significantly enhanced acute toxicity. CoQ10 pretreatment did not alter the antitumor effectiveness of adriamycin (i.p. or i.v.) against the Dunn osteosarcoma.

Topics: Animals; Body Weight; Doxorubicin; Female; Lung Neoplasms; Male; Mice; Mice, Inbred C3H; Sarcoma, Experimental; Ubiquinone

Effect of BCG, coenzyme Q10, or their combination on ATPase activity in spleen lymphocytes of tumor-bearing rats was investigated in relation to changes in the content of individual coenzyme Q homologs in these cells. Contents of both coenzyme Q9 and Q10 in spleen lymphocytes significantly decreased in the late stage of Donryu rats bearing Sato lung carcinoma. Oligomycin-sensitive ATPase activity in spleen lymphocytes was also significantly depressed in this stage. The depressed, oligomycin-sensitive ATPase activity was significantly recovered by a 3-time intramuscular administration of coenzyme Q10 emulsified with ethanol and saline, and the decreased contents of coenzymes Q9 and Q10 were slightly restored by this treatment. This enzyme activity was also significantly recovered by an intravenous administration of BCG, and was elevated more by the combined treatment with BCG and the emulsified coenzyme Q10. These results suggest that the combined treatment with BCG and emulsified coenzyme Q10 can contribute to the improvement of the depressed bioenergetics in lymphocytes of tumor-bearing animals, and that this combined effect of BCG and emulsified coenzyme Q10 might be based on the combination of their individual activating effect on lymphocytes.

Topics: Adenosine Triphosphatases; Animals; BCG Vaccine; Cells, Cultured; Lung Neoplasms; Lymphocytes; Male; Neoplasms, Experimental; Rats; Rats, Inbred Strains; Spleen; Ubiquinone