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Life Extension Magazine

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Pomegranate, magnesium-L-threonate (MgT), Vitamin D, Male sexual health, AND Microbiome health

June 2018


Paraoxonase 1 (PON1) as a marker of short term death in breast cancer recurrence.

OBJECTIVE: To relate paraoxonase (PON1) activity to survival time and short term death in breast cancer recurrence. DESIGN AND METHODS: PON1 activity was measured by its rate of hydrolysis of two different substrates, paraoxon (PON) and phenylacetate (ARE) in 50 patients with recurrence of breast cancer. Results were compared between patients surviving more than one year after the analysis (22) and those who died within one year (28). RESULTS: In a logistic regression analysis, ARE was negatively associated with early death (OR=0.10 [0.02-0.58], p=0.0109). PON did not reach significance (OR=0.43 [0.17-1.11], p=0.0826). In a multiple logistic regression analysis model, ARE was independently associated with early death (OR=0.12 [0.02-0.98], p=0.0476), besides interval time between diagnosis and recurrence (OR=0.54 [0.27-1.07], p=0.0781) and undernutrition (OR=3.95 [0.81-19.19], p=0.0883). CONCLUSION: Paraoxonase is a potential marker of survival in patients with breast cancer recurrence.

J Clin Biochem. 2012 Nov;45(16-17):1503-5.

Serum paraoxonase and arylesterase activities in patients with epithelial ovarian cancer.

OBJECTIVE: The HDL-associated paraoxonase and arylesterase activities play a role in decreasing oxidative stress, which is known to contribute to cancer development. The aim of this study was to evaluate serum paraoxonase and arylesterase activities and lipid hydroperoxide (LOOH) levels in patients with newly-diagnosed epithelial ovarian cancer. MATERIALS: Serum paraoxonase and arylesterase activities, total free sulfhydryl (-SH) levels and LOOH levels were measured in patients with epithelial ovarian cancer (n=24) and controls (n=29). RESULTS: Serum paraoxonase activity and arylesterase activity, as well as -SH levels were significantly lower (p=0.003, p<0.001 and p<0.001, respectively) in patients with epithelial ovarian cancer compared to controls, while LOOH levels were significantly higher (p<0.001). A significant inverse correlation was found between the stage, grade and CA-125 level of ovarian cancer and paraoxonase activity (rho=-0.630, p=0.001 and rho=-0.601, p=0.002 and rho=-0.436, p=0.033, respectively), arylesterase activity (rho=-0.601, p=0.002 and rho=-0.713, p<0.001 and rho=-0.580, p=0.003, respectively), and -SH levels (rho=-0.642, p=0.001 and rho=-0.637, p=0.001 and rho=-0.530, p=0.008, respectively). In contrast, there was a positive correlation between LOOH and the stage, grade and CA-125 level of ovarian cancer (rho=0.565, p=0.004 and rho=0.479, p=0.018 and rho=0.642, p=0.001). CONCLUSION: Our results suggest that diminished paraoxonase and arylesterase activity, -SH levels and increased LOOH levels are associated with particular stage, grade and CA-125 level of ovarian cancer.

Gynecol Oncol. 2009 Mar;112(3):481-5.

Serum 8-isoprostane levels and paraoxonase 1 activity in patients with stage I multiple myeloma.

OBJECTIVE: Multiple myeloma (MM) is a plasma cell malignancy comprising 15% of hematological malignancies. Many studies have assessed the relationship between free radicals and tumor progression or cancer risk. We aimed to evaluate the antioxidant activity of paraoxonase 1 (PON1), arylesterase (ARE), and 8-isoprostane in patients with stage I MM. MATERIALS AND METHODS: Spectrophotometric assays of serum PON1 and ARE activities in addition to serum 8-isoprostane level were performed in 34 patients newly diagnosed with stage I MM as compared to 35 age- and sex-matched individuals who comprised the healthy control group. RESULTS: A significant reduction was found in the activities of PON1 and ARE (for both, P < 0.001) in the patient group. The ratio of PON1/high-density lipoprotein was significantly lower in the MM patient group than in the control group (P < 0.001), while 8-isoprostane levels compared with the control group were significantly higher (P < 0.001), observations that may indicate an increase in oxidative stress in stage I MM patients. CONCLUSION: A decrease in PON1 activity and increase in 8-isoprostane serum activities in patients may indicate the importance of lipid peroxidation in MM disease. Oxidative stress and especially lipid peroxidation could reduce the antioxidant activity of PON1 and ARE in MM patients and could be considered as factors in the pathogenesis of MM disease.

Redox Rep. 2016 Sep;21(5):204-8.

Paraoxonase and arylesterase activities in patients with papillary thyroid cancer.

OBJECTIVE: The aim of this study was to evaluate paraoxonase-1 (PON1) activities and oxidative stress status, and the changes in their levels after total thyroidectomy in patients with papillary thyroid cancer (PTC). MATERIALS AND METHODS: Twenty-five patients with PTC and 27 healthy controls were enrolled in the study. Blood samples were obtained from the PTC patients before and 3 months after the operation. Preoperative and postoperative serum samples from PTC patients and healthy controls were analyzed for paraoxonase (PON), arylesterase (ARE) activities, and lipid hydroperoxide (LOOH) and -SH (total free sulfhydryl) levels. RESULTS: The preoperative PON, ARE and -SH levels of the patients with PTC were significantly lower compared to those of the control group (p = 0.033, p < 0.001, p = 0.002, respectively), while LOOH levels were significantly higher (p < 0.001). The levels of PON and ARE decreased significantly in patients with PTC after the operation (p = 0.038, p = 0.023, respectively), while LOOH and -SH levels remained unchanged (p = 0.117, p = 0.487, respectively). PON and ARE levels showed a positive correlation with -SH (r = 0.211, p = 0.065; r = 0.471, p < 0.001, respectively) and a negative correlation with LOOH (r = - 0.391, p < 0.001, r = - 0.486, p < 0.001, respectively). CONCLUSION: Serum PON1 activity is decreased in patients with PTC, and serum PON1 is positively correlated with -SH, a well-known antioxidant, and negatively correlated with LOOH, an oxidant. PON1 activity is significantly decreased after total thyroidectomy.

Scand J Clin Lab Invest. 2015 May;75(3):259-64.

Measurement of serum paraoxonase activity and MDA concentrations in patients suffering with oral squamous cell carcinoma.

BACKGROUND: Oxidative stress is associated with many diseases including cancer. Oral squamous cell carcinoma (OSCC) is a prevalent cancer involving oral cavity. We evaluate the activity of paraoxonase 1 (PON1) in serum samples of subjects suffering from OSCC along with malondialdehyde (MDA) levels, a marker for oxidative stress. Antioxidant status in OSCC may reflect the role of oxidative imbalance in the disease. METHODS: Forty-five patients suffering with OSCC and 30 healthy controls were selected for the study. Serum paraoxonase (PON) and arylesterase (ARE) activities were measured in subjects suffering from OSCC and their healthy counterparts. To examine the status of lipid peroxidation, MDA concentrations were estimated and a correlation was determined between PON activities and MDA concentrations. MDA expression in cancer and normal adjacent tissue was studied through immunohistochemical (IHC) analysis. Total reactive oxygen species (ROS) level was determined in serum from normal and diseased subjects. Our results revealed that both PON and ARE activities of PON1 were significantly decreased in OSCC patients. Serum MDA concentrations were inversely correlated to PON activity. Immunohistochemical analysis showed a higher expression of MDA in cancerous tissue. Total ROS levels were found to be significantly elevated in cancer subjects. CONCLUSIONS: Along with other antioxidants, PON levels may act as an indicator of oxidative stress in cancer.

Clin Chim Acta. 2014 Mar 20;430:38-42

Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer.

Prostate cancer is the most common invasive malignancy and the second leading cause of cancer-related deaths among U.S. males, with a similar trend in many Western countries. One approach to control this malignancy is its prevention through the use of agents present in diet consumed by humans. Pomegranate from the tree Punica granatum possesses strong antioxidant and antiinflammatory properties. We recently showed that pomegranate fruit extract (PFE) possesses remarkable antitumor-promoting effects in mouse skin. In this study, employing human prostate cancer cells, we evaluated the antiproliferative and proapoptotic properties of PFE. PFE (10-100 microg/ml; 48 h) treatment of highly aggressive human prostate cancer PC3 cells resulted in a dose-dependent inhibition of cell growth/cell viability and induction of apoptosis. Immunoblot analysis revealed that PFE treatment of PC3 cells resulted in (i) induction of Bax and Bak (proapoptotic); (ii) down-regulation of Bcl-X(L) and Bcl-2 (antiapoptotic); (iii) induction of WAF1/p21 and KIP1/p27; (iv) a decrease in cyclins D1, D2, and E; and (v) a decrease in cyclin-dependent kinase (cdk) 2, cdk4, and cdk6 expression. These data establish the involvement of the cyclin kinase inhibitor-cyclin-cdk network during the antiproliferative effects of PFE. Oral administration of PFE (0.1% and 0.2%, wt/vol) to athymic nude mice implanted with androgen-sensitive CWR22Rnu1 cells resulted in a significant inhibition in tumor growth concomitant with a significant decrease in serum prostate-specific antigen levels. We suggest that pomegranate juice may have cancer-chemopreventive as well as cancer-chemotherapeutic effects against prostate cancer in humans.

Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14813-8