Blog Archives
Effect of Chemotherapeutics and Tocopherols on MCF-7 Breast Adenocarcinoma and KGN Ovarian Carcinoma Cell Lines In Vitro
Figueroa D, Asaduzzaman M, Young F
Biomed Res Int. 2019 Jan 15;2019:6146972. doi: 10.1155/2019/6146972. eCollection 2019.
Abstract
The combination of doxorubicin and cyclophosphamide commonly used to treat breast cancer can cause premature ovarian failure and infertility. α–Tocopherol is a potent antioxidant whereas γ–tocopherol causes apoptosis in a variety of cancer models in vitro including breast cancer. We hypothesised that the combination of doxorubicin (Dox) and 4-hydroperoxycyclophosphamide (4-Cyc) would be more cytotoxic in vitro than each agent alone, and that α–tocopherol would reduce and γ–tocopherol would augment the cytotoxicity of the combined chemotherapeutics. Human MCF-7 breast cancer and KGN ovarian cells were exposed to Dox, 4-Cyc, combined Dox and 4-Cyc, α–tocopherol, γ–tocopherol, or a combination of Dox and 4-Cyc with α–tocopherol or γ–tocopherol. Cell viability was assessed using a crystal violet assay according to four schedules: 24h exposure, 24h exposure + 24h culture in medium, 24h exposure + 48h culture in medium, or 72h continuous exposure. Supernatants from each separate KGN culture experiment (n=3) were examined using an estradiol ELISA. Dox was cytotoxic to both MCF-7 and KGN cells, but 4-Cyc only killed MCF-7 cells. γ–Tocopherol significantly decreased MCF-7 but not KGN cell viability. The combined chemotherapeutics and γ–tocopherol were more cytotoxic to MCF-7 than KGN cells, and α–tocopherol reduced the cytotoxicity of the combined chemotherapeutics towards KGN ovarian cells, but not MCF-7 cells. The addition of both γ–tocopherol and α–tocopherol to the chemotherapeutic combination of Dox and cyclophosphamide has the potential to increase in vitro chemotherapeutic efficacy against breast cancer cells whilst decreasing cytotoxicity towards ovarian granulosa cells.
The effect of α-tocopherol and dithiothreitol in ameliorating emamectin benzoate cytotoxicity in human K562 cells involving the modulation of ROS accumulation and NF-κB signaling
Luan S, Muhayimana S, Xu J, Zhang X, Xiao C, Huang Q
Ecotoxicol Environ Saf. 2019 Jan 15;167:114-121. doi: 10.1016/j.ecoenv.2018.09.125. Epub 2018 Oct 10.
Abstract
Emamectin benzoate (EMB) toxicity contributes a potential risk to environment and human health. To investigate the effect of α-tocopherol(VitE) and dithiothreitol (DTT) in ameliorating EMB-induced cytotoxicity in human K562 cells, in vitro cultured human K562 cells were incubated with different concentrations of EMB in supplement with VitE and DTT when the cells were in the logarithmic phase. Next, the cell growth inhibition was evaluated using the MTT assay and cellular morphology observation. Reactive oxygen species (ROS) production was monitored using DCFH-DA probe and NF-κB signaling was determined using Western blotting. The results demonstrated that treatment with EMB (time- and concentration-dependent) showed significantly greater inhibition on K562 cell viability, heavier chromatin condensation and DNA fragmentation, and stronger suppression of NF-κB/p105 and p65/RelA expression of K562 cells than the control group (p < 0.01). The supplementation of VitE or DTT could help protect K562 cells against EMB-induced cytotoxicity by improving cell viability, preventing ROS accumulation and up-regulating NF-κB signaling through their ameliorating effects against oxidative stress induced by EMB. VitE had a stronger synergistic effect in limiting EMB cytotoxicity than DTT. Our findings indicate that VitE and DTT are potent antioxidants for human K562 cells, offering a promising means of ameliorating EMB cytotoxicity.
Tocotrienols and Cancer: From the State of the Art to Promising Novel Patents
Fontana F, Raimondi M, Marzagalli M, Moretti RM, Marelli MM, Limonta P
Recent Pat Anticancer Drug Discov. 2019 Jan 15. doi: 10.2174/1574892814666190116111827. [Epub ahead of print]
Abstract
BACKGROUND:
Tocotrienols (TTs) are vitamin E derivatives naturally occurring in several plants and vegetable oils. Like Tocopherols (TPs), they comprise four isoforms, α, β, γ and δ, but unlike TPs, they present an unsaturated isoprenoid chain. Recent studies indicate that TTs provide important health benefits, including neuroprotective, anti-inflammatory, anti-oxidant, cholesterol lowering and immunomodulatory effects. Moreover, they have been found to possess unique anti-cancer properties.
OBJECTIVE:
The purpose of this review is to present an overview of the state of the art of TTs role in cancer prevention and treatment, as well as to describe recent patents proposing new methods for TTs isolation, chemical modification and use in cancer prevention and/or therapy.
METHODS:
Recent literature and patents focusing on TTs anti-cancer applications have been identified and reviewed, with special regard to their scientific impact and novelty.
RESULTS:
TTs have demonstrated a significant anti-cancer activity in multiple tumor types, both in vitro and in vivo. Furthermore, they have shown synergistic effects when given in combination with standard anti-cancer agents or other anti-tumor natural compounds. Finally, new purification processes and transgenic sources have been designed in order to improve TTs production, and novel TTs formulations and synthetic derivatives have been developed to enhance their solubility and bioavailability.
CONCLUSION:
The promising anti-cancer effects shown by TTs in several preclinical studies may open new opportunities of therapeutic interventions in different tumors. Thus, clinical trials aimed at confirming TTs chemopreventive and tumor-suppressing activity, particularly in combination with standard therapies, are urgently needed.
Association Between Vitamin E and Cancer Affected by Genetics
Kathryn Hall, Ph.D., MPH, from the Division of Preventative Medicine at Brigham, was quoted as saying, “Observational studies of people taking vitamin E have reported benefits, and studies in animal models have suggested a protective effect, but when vitamin E supplements were brought into placebo-controlled clinical trials, the results were null. This made it easy to assume that vitamin E just doesn’t work. But what we’ve found is that it may have been protective in some and not in others, and that genetic variation is linked to these outcomes.
COMT gene modifies chemopreventive effects of vitamin E
Vitamin E supplementation may reduce the risk for cancer but only in individuals harboring a particular allele of the catechol-O-methyltransferase (COMT) gene, suggests an analysis of two randomized trials.
Tocotrienol-Rich Fraction (TRF) Treatment Promotes Proliferation Capacity of Stress-Induced Premature Senescence Myoblasts and Modulates the Renewal of Satellite Cells: Microarray Analysis
Lim JJ, Wan Zurinah WN, Mouly V, Norwahidah AK
Oxid Med Cell Longev. 2019 Jan 10;2019:9141343. doi: 10.1155/2019/9141343. eCollection 2019.
Abstract
Human skeletal muscle is a vital organ involved in movement and force generation. It suffers from deterioration in mass, strength, and regenerative capacity in sarcopenia. Skeletal muscle satellite cells are involved in the regeneration process in response to muscle loss. Tocotrienol, an isomer of vitamin E, was reported to have a protective effect on cellular aging. This research is aimed at determining the modulation of tocotrienol-rich fraction (TRF) on the gene expressions of stress-induced premature senescence (SIPS) human skeletal muscle myoblasts (CHQ5B). CHQ5B cells were divided into three groups, i.e., untreated young control, SIPS control (treated with 1 mM hydrogen peroxide), and TRF-posttreated groups (24 hours of 50 μg/mL TRF treatment after SIPS induction). The differential gene expressions were assessed using microarray, GSEA, and KEGG pathway analysis. Results showed that TRF treatment significantly regulated the gene expressions, i.e., p53 (RRM2B, SESN1), ErbB (EREG, SHC1, and SHC3), and FoxO (MSTN, SMAD3) signalling pathways in the SIPS myoblasts compared to the SIPS control group (p < 0.05). TRF treatment modulated the proliferation capacity of SIPS myoblasts through regulation of ErbB (upregulation of expression of EREG, SHC1, and SHC3) and FoxO (downregulation of expression of MSTN and SMAD3) and maintaining the renewal of satellite cells through p53 signalling (upregulation of RRM2B and SESN1), MRF, cell cycle, and Wnt signalling pathways.
What dictates how vitamin E supplements affect cancer risk?
There is a longstanding debate as to whether taking vitamin E supplements increases or decreases a person’s risk of developing cancer. A new study suggests that both outcomes are a possibility and also explains why.
Improvement of Serum Biochemical Parameters and Hematological Indices Through α-Tocopherol Administration in Dietary Oxidized Olive Oil Induced Toxicity in Rats
Zeb A, Khan AA
Front Nutr. 2019 Jan 10;5:137. doi: 10.3389/fnut.2018.00137. eCollection 2018.
Abstract
Dietary oxidized olive oil, alone or in combination with different doses of α-tocopherol, were given to Swiss albino rats for 30 days; in order to determine its role in oxidative stress and fatty liver, induced by the oxidized olive oils. Serum biochemical parameters and hematological indices of blood were analyzed. The liver was analyzed for histopathological changes, lipid peroxidation, and polar triacylglycerols composition. Results revealed that there was a significant decline in the serum total cholesterol, triglycerides, LDL, glucose and ALT; while a significant increase occurred in the serum HDL levels through the supplementation of α-tocopherol in male and female rats. Hematological parameters were almost in the normal reference range in the groups that were fed α-tocopherol, alone or in combination with oxidized oil, while being significantly altered by the oxidized olive oil. There were acute hepatitis and necrosis in the liver with no fatty changes after feeding with oxidized olive oil, along with varying doses of α-tocopherol. Higher amounts of polar compounds were present in female rats (15.2-93.1 μg/g) compared to male rats (12.2-82.3%) that correspond to the supplementation of α-tocopherol in combination with oxidized oil. Lipid oxidation in liver was minimized by tocopherol, while an increase occurred in the accumulation of oxidized lipids in the liver. These findings revealed that tocopherol is beneficial against the oxidized oil induced biochemical and hematological changes and lipid peroxidation but causes fatty accumulation in the liver. Therefore, the role of tocopherol in patients with fatty liver disease may be considered, as tocopherol may increase the chance of survival.
The effects of omega-3 fatty acids and vitamin E co-supplementation on gene expression related to inflammation, insulin and lipid in patients with Parkinson’s disease: A randomized, double-blind, placebo-controlled trial
Tamtaji OR, Taghizadeh M, Aghadavod E, Mafi A, Dadgostar E, Daneshvar Kakhaki R, Abolhassani J, Asemi Z
Clin Neurol Neurosurg. 2019 Jan;176:116-121. doi: 10.1016/j.clineuro.2018.12.006. Epub 2018 Dec 8.
Abstract
OBJECTIVE:
This study was conducted to evaluate the effects of omega-3 fatty acids and vitamin E co-supplementation on gene expression related to inflammation, insulin and lipid in subjects with Parkinson’s disease (PD).
PATIENTS AND METHODS:
This randomized, double-blind, placebo-controlled clinical trial was performed in 40 subjects with PD. Participants were randomly allocated into two groups to take either 1000 mg/day of omega-3 fatty acids from flaxseed oil plus 400 IU/day of vitamin E supplements or placebo (n = 20 each group) for 12 weeks. Gene expression related to inflammation, insulin and lipid were quantified in peripheral blood mononuclear cells (PBMC) of PD patients with RT-PCR method.
RESULTS:
After the 12-week intervention, compared with the placebo, omega-3 fatty acids and vitamin E co-supplementation downregulated gene expression of tumor necrosis factor alpha (TNF-α) (P = 0.002) in PBMC of subjects with PD. In addition, omega-3 fatty acids and vitamin E co-supplementation upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) (P = 0.03), and downregulated oxidized low-density lipoprotein receptor (LDLR) (P = 0.002) in PBMC of subjects with PD compared with the placebo. We did not observe any significant effect of omega-3 fatty acids and vitamin E co-supplementation on gene expression of interleukin-1 (IL-1) and IL-8 in PBMC of patients with PD.
CONCLUSIONS:
Overall, omega-3 fatty acids and vitamin E co-supplementation for 12 weeks in PD patients significantly improved gene expression of TNF-α, PPAR-γ and LDLR, but did not affect IL-1 and IL-8.