Chemo-Preventive Effect of 1-Piperoyl Piperidine (Piperine) Is Mediated Through Intrinsic Signaling Mechanisms In Human Prostate Cancer Cells (Pc-3) In Vitro

Background: Prostate cancer is a heterogeneous disease and it is second deadliest malignancy in men and the most commonly diagnosed cancer among men. Current chemo-therapies are limited due to considerable side effects. Recently, many kinds of bioactive phytochemicals have contributed significantly to developing new therapies for chemo-resistant prostate cancer due to their structural diversity. Piperine, a natural alkaloid found in the fruit of black (Piper nigrum Linn) and long (Piper longum Linn), has shown antitumor activities toward various cancer cell lines. However, the antitumor effects of piperine on intrinsic and extrinsic signaling mechanisms in breast cancer has not been elucidated so far. Aim: The study aimed to assess the anticancer activity of piperine in human prostate cancer cells through intrinsic signaling pathways. Methodology: Prostate cancer (PC3) cells were treated with different concentrations of piperine (100 & 200µg/ml) to analyze Bcl-2, p53, case pase-3 and caspase-9 protein expression in PC-3 cells. Cell viability was done using MTT in order to find the optimal dose. Results: MTT assay exhibited that piperine showed cell death at the concentration of 100 and 200µg. It significantly decreased the mRNA and protein expression of anti-apoptotic proteins (Bcl-2 and p-Bcl-2) and increased the levels of p53, casepase-3 and 9 protein expression in both concentrations used. Conclusion: Our present findings show that piperine induces apoptosis in PC-3 cells by inhibition the expression of anti-apoptotic proteins with concomitant increase in the tumor suppressor proteins effectively. Hence, piperine can be considered as a potential phototherapeutic drug for the treatment of prostate cancer which may lead to clinical utility.

Immunomodulatory and antiangiogenic mechanisms of polymolecular botanical drug extract C5OSEW5050ESA OS derived from Orthosiphon stamineus

NuvastaticTM is a polymolecular botanical drug formulation containing a proprietary extract of a selected cultivar of Orthosiphon stamineus (OS) code name, C5OSEW5050ESA OS. The anti-angiogenic activity of C5OSEW5050ESA OS was explored by evaluating its activity towards a variety of angiogenesis modulators in vitro and in vivo. Multiplex immunoassays reveals that C5OSEW5050ESA OS inhibits Vascular Endothelial Growth factor (VEGF), Epidermal Growth Factor (EGF), Fibroblast Growth Factor (FGF), Interleukin 2 ( IL-2) & Interleukin 7 (IL-7), Nerve Growth Factor β (NGF-β) , Transforming Growth Factor -α (TGF-α) and Tumor Necrosis Factor- β (TNF-β). C5OSEW5050ESA OS also caused significant upregulation of interferon α (IFN-α), interferon β (IFN-β), interferon γ (IFN-γ) and Granulocyte-macrophage colony-stimulating factor (GM-CSF). C5OSEW5050ESA OS was found to inhibit endothelial cell proliferation and migration (92.6%) and disrupts the tube assembly (98.26%) for new blood vessel formation. The compound also inhibits neovascularisation in isolated rat aortic ring tissues (IC50 18.2 ± 2 µg/mL) and in chick chorioallantoic membrane assays (CAM) by 82.7%. In vivo matrigel plug assay treated with C5OSEW5050ESA OS shows inhibition of neovascularisation by 91.4± 3%. In conclusion, the study reveals that C5OSEW5050ESA OS has strong anti-angiogenic and immunomodulatory properties which may have significant clinical benefits in cancer therapy.