Formononetin and Dihydroartemisinin Act Synergistically to Induce Apoptosis in Human Acute Myeloid Leukemia Cell Lines

Objective: Enhanced cell survival and drug resistance in tumor cells have been linked to the overexpression of antiapoptoticmembers of the Bcl-2 family proteins, including Bcl-2 and Mcl-1. The aim of this study was to explore theimpact of formononetin and dihydroartemisinin combination on the growth and apoptosis of acute myeloid leukemia(AML) cells.Materials and Methods: In this experimental study, the cell survival and cell proliferation were tested by MTT assay andtrypan blue staining. The evaluation of cell apoptosis was conducted using Hoechst 33342 staining and a colorimetricassay to measure caspase-3 activity. To determine the mRNA levels of Mcl-1, Bcl-2, Bax, and Cyclin D1, a quantitativereal-time polymerase chain reaction (qRT-PCR) was performed.Results: We showed that treatment with either formononetin or dihydroartemisinin alone, led to significant decreasein the cell survival and growth, and triggered apoptosis in U937 and KG-1 AML cell lines. Moreover, treatment witheach of the compounds alone significantly decreased the mRNA levels of Mcl-1, Bcl-2 and Cyclin D1 mRNA, while, theexpression level of Bax mRNA was enhanced. Combination of two compounds showed a synergistic anti-cancer effect.Conclusion: The anti-leukemic potential of formononetin and dihydroartemisinin is exerted through the effect on cellcycle progression and intrinsic pathway of apoptosis. Therefore, they can be considered as a potential anti-leukemicagent alone or along with existing chemotherapeutic drugs

Frequency of IL-10+CD19+ B cells in patients with prostate cancer compared to patients with benign prostatic hyperplasia

Background: The function of the immune system in prostate cancer (PC) might promote carcinogenesis. PC is a common cancer in men. Regulatory B cells (Bregs) are a new subtype of B cells that have suppressive roles in the immune system. Interleukin-10 (IL-10) is a dominant mediator of immune suppression released by Bregs. Objective: The purpose of this research was to examine the frequency of CD19+IL10+ B cells and IL-10 mRNA expression in patients with PC compared to patients with benign prostatic hyperplasia (BPH). Methods: Forty paraffin tissue samples from patients with PC and 32 paraffin tissue samples from patients with BPH were entered in this study. The immunohistochemistry staining was used to evaluate the pattern expression of CD19 and IL-10 markers. IL-10 mRNA expression in fresh tissue was determined by real time-polymerase chain reaction (RT-PCR). Results: The frequency of CD19+IL-10+ B cells and IL-10 mRNA expression in PC patients were significantly higher than patients with BPH. Also, there was no meaningful relationship between the frequency of IL-10+CD19+ B cells and gleason scores in patients with PC. Conclusions: Our findings suggested that frequency of IL-10+CD19+ B cells correlates with progressive stage of PC

Frequency of IL-10+CD19+ B cells in patients with prostate cancer compared to patients with benign prostatic hyperplasia

Background: The function of the immune system in prostate cancer (PC) might promote carcinogenesis. PC is a common cancer in men. Regulatory B cells (Bregs) are a new subtype of B cells that have suppressive roles in the immune system. Interleukin-10 (IL-10) is a dominant mediator of immune suppression released by Bregs. Objective: The purpose of this research was to examine the frequency of CD19+IL10+ B cells and IL-10 mRNA expression in patients with PC compared to patients with benign prostatic hyperplasia (BPH). Methods: Forty paraffin tissue samples from patients with PC and 32 paraffin tissue samples from patients with BPH were entered in this study. The immunohistochemistry staining was used to evaluate the pattern expression of CD19 and IL-10 markers. IL-10 mRNA expression in fresh tissue was determined by real time-polymerase chain reaction (RT-PCR). Results: The frequency of CD19+IL-10+ B cells and IL-10 mRNA expression in PC patients were significantly higher than patients with BPH. Also, there was no meaningful relationship between the frequency of IL-10+CD19+ B cells and gleason scores in patients with PC. Conclusions: Our findings suggested that frequency of IL-10+CD19+ B cells correlates with progressive stage of PC

Dual Targeting of Anti-Apoptotic Proteins Enhances Chemosensitivity of the Acute Myeloid Leukemia Cells

BACKGROUND: Acute myeloid leukemia (AML) is a type of blood cancer characterized by fast cellular proliferation. Myeloid cell leukemia-1 (Mcl-1) and survivin, as anti-apoptotic proteins, are involved in cancer growth and resistance to chemotherapy. The aim of this study was to examine the combination effect of Mcl-1 and survivin specific siRNAs on chemosensitivity of the human HL-60 AML cells. METHODS: SiRNAs transfection was performed by using Lipofectamine™2000 reagent. The mRNA expression was analyzed by real-time quantitative PCR. The apoptosis analysis was measured by ELISA cell death assay. RESULTS: siRNAs markedly suppressed mRNA expression levels of Mcl-1 and survivin in a time-dependent manner, resulting in reduction of leukemic cell proliferation and enhanced spontaneous cell death. Surprisingly, Mcl-1 siRNA and survivin siRNA synergistically enhanced the cell toxic effects of etoposide. Furthermore, down-regulation of Mcl-1 and survivin significantly enhanced the apoptotic effect of etoposide. CONCLUSIONS: Our investigation suggests that suppression of Mcl-1 and survivin by siRNA can effectually inhibit cell growth and overcome chemoresistance of AML cells. Therefore siRNAs may be an important adjuvant in chemotherapy for AML patients

Comparing the frequency of CD33(+) pSTAT3(+) myeloid-derived suppressor cells and IL-17(+) lymphocytes in patients with prostate cancer and benign prostatic hyperplasia

Prostate cancer (PCa) is one of the most epidemic types of cancer in men. The tumor microenvironment (TME) of PCa is involved in the emergence of immunosuppressive factors such as myeloid-derived suppressor cells (MDSC), which regulate the immune system by several mechanisms, including interleukin (IL)-10 production. On the other hand, IL-17(+) helper T cells (Th17) induce MDSCs and chronic inflammation in TME by producing IL-17. This study demonstrated that the frequency of CD33(+) pSTAT3(+) MDSC and IL-17(+) lymphocyte as well as IL-10 messenger RNA (mRNA) expression were significantly higher in the PCa patients than in the benign prostatic hyperplasia (BPH) group. Moreover, there was no significant relationship between the frequency of CD33(+) pSTAT3(+) MDSC, and IL-17(+) lymphocyte with Gleason scores in the PCa group. We suggested that the higher frequency of CD33(+) pSTAT3(+) MDSC and IL-17(+) lymphocyte and the more frequent expression of IL-10 mRNA in PCa patients may play roles in tumor progression from BPH to PCa