Dr. Ron’s Research Review – May 10, 2017

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This week’s research review focuses on Thymax, gross thymic extract

 

A study published in Anticancer Research showed that Thymax (gross thymic extract) induces apoptosis in human breast cancer (MCF-7) cells in vitro through the mitochondrial pathway. (Ghoneum et al., 2008)

Another study published in Anticancer Research showed that Thymax activates human monocyte-derived dendritic cells (DCs) in vitro. Thymax activated DCs to secrete interleukin (IL)-12p40 and IL-6 cytokines and inhibited IL-10 production. Additionally, Thymax caused the up-regulation of CD80 and CD86 in DCs, leading to an increase in CD4(+) T-cells, which subsequently induced secretion of interferon-gamma (IFN-gamma). Thus, Thymax is an immune-activating compound. (Ghoneum et al., 2009a)

A study published in In Vivo showed that Thymax corrected age-associated functional decline in murine immune cells. Treatment with Thymax resulted in: i) a significant increase in the percentages of DCs (1.6-fold), B-cells (7-fold) and T-cells (5-fold) over the control (p<0.05); ii) an increase in the percentages of activation markers (CD25 and CD69) of CD4(+) and CD8(+) T-cells; and iii) an enhancement in NK activity. Thymax showed no adverse side-effects. Thymax might have a role in reversing immune dysfunction in the elderly. (Ghoneum et al., 2009b)

 

Dr. Ron

 


Articles

 

Gross thymic extract, Thymax, induces apoptosis in human breast cancer cells in vitro through the mitochondrial pathway.
            (Ghoneum et al., 2008) Download
Previous studies have shown that thymic extracts possess antitumor and antimetastatic properties, but the mechanisms are not completely understood. Therefore, in this study the ability of the gross thymic extract Thymax to induce apoptosis in human breast cancer cell line (MCF-7) cells in vitro was evaluated. Tumor cells were cultured with different concentrations of Thymax for 24 h and the apoptotic response was assessed by propidium iodide and TUNEL assays. Activation of caspases and changes in mitochondrial membrane potential (MMP) were monitored by flow cytometry and the expression of Bcl-2 and Bax was determined by Western blot analysis. Thymax induced apoptosis in monolayer MCF-7 cells in a dose-dependent manner; at concentrations of 2.5, 5 and 10% (v/v) it caused 9%, 10% and 25% apoptosis, respectively, as compared to 6% for control cancer cells without treatment. The induction of apoptosis by Thymax was associated with activation of caspases 8 and 9, and the addition of a pan caspase inhibitor partially inhibited Thymax-induced apoptosis by 20%. In addition, the MMP was decreased significantly at Thymax concentrations of 5%-20%, which was associated with a decrease in the protein expression of Bcl-2 and an increase in Bax. These results suggest that Thymax exerts its effects via the mitochondrial pathway of apoptosis and may represent a new class of adjuvants for the treatment of breast cancer.

Activation of human monocyte-derived dendritic cells in vitro by Thymax, a gross thymic extract.
            (Ghoneum et al., 2009a) Download
BACKGROUND:  We have recently demonstrated that Thymax, a gross thymic extract, induces an apoptotic effect against human breast cancer cells. In this study, the ability of Thymax to activate human dendritic cells (DCs) and the DC-directed T-cell response was examined in an in vitro culture model of peripheral blood mononuclear cells. MATERIALS AND METHODS:  The level of costimulatory molecules (CD40, CD80, CD83, CD86) and T-cell proliferation were analyzed by flow cytometry. Cytokine secretion was measured by ELISA. RESULTS:  Thymax activated DCs to secrete interleukin (IL)-12p40 and IL-6 cytokines and inhibited IL-10 production. Additionally, Thymax caused the up-regulation of CD80 and CD86 in DCs, leading to an increase in CD4(+) T-cells, which subsequently induced secretion of interferon-gamma (IFN-gamma). CONCLUSION:  Taken together, the data showed that Thymax activated DCs and, consequently, Th1 cells. Thus, Thymax is an immune-activating compound that needs to be evaluated extensively for its possible therapeutic properties.

Phenotypic correction of Age-associated functional decline in murine immune cells by Thymax, a thymic extract.
            (Ghoneum et al., 2009b) Download
BACKGROUND:  We have recently demonstrated that Thymax, a gross thymic extract, induces the functional activity of human dendritic cells (DCs) in vitro. In this study, the role of Thymax in phenotypic correction of age-associated functional decline in immune cells in mice was evaluated. MATERIALS AND METHODS:  C57BL/6 mice (13 months old) were treated with Thymax orally (20% v/v) for 4 weeks. Different splenic cell types, dendritic cells (DCs), B-cells, T-cells and natural killer (NK) cells, were analyzed using flow cytometry. RESULTS:  Treatment with Thymax resulted in: i) a significant increase in the percentages of DCs (1.6-fold), B-cells (7-fold) and T-cells (5-fold) over the control (p<0.05); ii) an increase in the percentages of activation markers (CD25 and CD69) of CD4(+) and CD8(+) T-cells; and iii) an enhancement in NK activity. Thymax showed no adverse side-effects. CONCLUSION:  Thymax might have a role in reversing immune dysfunction in the elderly.

 

References

Ghoneum, M, et al. (2008), ‘Gross thymic extract, Thymax, induces apoptosis in human breast cancer cells in vitro through the mitochondrial pathway.’, Anticancer Res, 28 (3A), 1603-9. PubMed: 18630518
Ghoneum, M, Y Seto, and S Agrawal (2009a), ‘Activation of human monocyte-derived dendritic cells in vitro by Thymax, a gross thymic extract.’, Anticancer Res, 29 (11), 4367-71. PubMed: 20032380
Ghoneum, M, L Tolentino, and Y Seto (2009b), ‘Phenotypic correction of Age-associated functional decline in murine immune cells by Thymax, a thymic extract.’, In Vivo, 23 (6), 895-902. PubMed: 20023230