Original articleThe extract from Punica granatum (pomegranate) peel induces apoptosis and impairs metastasis in prostate cancer cells
Introduction
Cancer is the leading cause of death in the 21st century. According to American Cancer Society, prostate cancer is the most common form of cancer in male, accounting for 1 in 5 new cancer diagnoses in men and ranking the second leading cause of cancer related mortality [1]. Unfortunately, the majority of prostate cancer patients are diagnosed at a late stage with distant metastasis but its pathogenesis is not fully understood yet, resulting a high mortality [2], [3]. Thus, there is an urgent need to uncover the molecular mechanisms of prostate cancer (PCa) and to develop some novel and better therapeutic approaches.
Punica granatum (Pomegranate) is one member of Punicaceae. The peel juice and seed oil of the pomegranate fruit is an important source of antioxidants with known anti-cancer activities [4]. Numerous current researches have demonstrated that antioxidants in some fruits and vegetables can defend human cells from oxidative damage and prevent aging, resulting in a decreased incidence of tumors and infections [5]. There are plenty of bioactive components presented in pomegranate peel, such as tannins, flavonoids, polyphenols, anthocyanins, etc. [4]. They have been proposed to have various pharmacological activities, including anticancer activity.
Evasion of apoptosis is one hallmark of maybe all types of cancer [6]. Deregulation of apoptosis resulted in uncontrolled growth of cancer and development of resistance to treatment. Therefore, drugs that could restore cancer cell apoptosis may be effective against many types of cancer, making this a promising strategy to treat cancer [7]. On April 11, 2016, the U. S. Food and Drug Administration approved Venclexta for treating chronic lymphocytic leukemia (CML) patients. This is a Bcl2 inhibitor that specifically targeted to the apoptosis pathway.
It has been proved in earlier studies that pomegranate peel could inhibit prostate cancer growth by inducing cell apoptosis [8]. However, the mechanism of pomegranate peel induced apoptosis has not been delineated clearly yet. Metastasis is the main cause of PCa related mortality. Migration and invasion are two critical steps in metastasis. Numerous proteins are involved in the metastasis cascades. Among them, matrix metalloproteinases could destruct the integraty of extracellular matrix in the microenvironment to facilitate metastasis [9], [10]. It’s still unknown whether pomegranate peel extract (PoPx) could inhibit PCa metastasis cascades. Hence, this study is aimed to investigate the effects of PoPx on PCa cells and provide evidence for the further application of PoPx in inhibiting PCa growth and metastasis. The effects of PoPx were assessed on several PCa cells and the preliminary molecular mechanism was explored in our study.
Section snippets
Preparation of pomegranate peel extract (PoPx)
Pomegranate peel of Tunisia soft-seed pomegranate was purchased from Yuzhuang Ecological Green Industry Co. (Qianxi County, Guizhou Province, China). The preparation of pomegranate peel extract was done as previously described with minor modifications. Firstly, 400 g fresh peel was cut into pieces of 0.5 cm in size and extracted with a combination of 1550 mL ethanol and 480 mL H2O followed by soaking for 2 h at 60 °C. The crude extracts were then filtered and concentrated under vacuum to produce a
Analysis of punicalagin and ellagic acid in PoPx by HPLC and MS
PoPx was comprehensively analyzed by the combination of HPLC and MS. The prepared PoPx sample was firstly analyzed by using the optimized HPLC method and the component were matched by the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine (Version 2012A). As shown in Fig. 1A, the main constituents of PoPx were determined as punicalagin (PC, peak 1 and peak 2) and ellagic acid (EA, peak 3) by comparing their retention time with standard substance. The
Discussion
Prostate cancer is a big threat to male and lacks effective treatment option. And a lot of pharmaceutical companies and institutes are trying to find novel drugs to treat this devastating disease. Numerous research reports that natural compounds from plants can trigger apoptosis in a lot of cancer cells with different histologic origin [18]. This inspires us to investigate the pharmacological activities of extracts from pomegranate peels on prostate cancer.
Dysregulation of apoptosis is a
References (35)
- et al.
Evaluation of antioxidant properties of pomegranate peel extract in comparison with pomegranate pulp extract
Food Chem.
(2006) - et al.
Hallmarks of cancer: the next generation
Cell
(2011) - et al.
Gene therapy of cancer with interferon: lessons from tumor models and perspectives for clinical applications
Semin. Cancer Biol.
(2000) - et al.
Punica granatum (pomegranate) leaves extract induces apoptosis through mitochondrial intrinsic pathway and inhibits migration and invasion in non-small cell lung cancer in vitro
Biomed. Pharmacother.
(2016) - et al.
Advances in wound-healing assays for probing collective cell migration
J. Lab. Autom.
(2012) - et al.
Ursolic acid sensitizes prostate cancer cells to TRAIL-mediated apoptosis
Biochim. Biophys. Acta
(2013) - et al.
Pyrogallol-induced calf pulmonary arterial endothelial cell death via caspase-dependent apoptosis and GSH depletion
Food Chem. Toxicol.
(2010) - et al.
Pathway of programmed cell death in HeLa cells induced by polymeric anti-cancer drugs
Biomaterials
(2011) - et al.
Disruption of mitochondrial function during apoptosis is mediated by caspase cleavage of the p75 subunit of complex I of the electron transport chain
Cell
(2004) - et al.
Baicalein protects Human melanocytes from H2O2-induced apoptosis via inhibiting mitochondria-dependent caspase activation and the p38 MAPK pathway
Free Radic. Biol. Med.
(2012)
Mechanisms of caspase activation and inhibition during apoptosis
Mol. Cell
Pomegranate peel extract polyphenols induced apoptosis in human hepatoma cells by mitochondrial pathway
Food Chem. Toxicol.
Gene therapy of cancer with interferon: lessons from tumor models and perspectives for clinical applications
Semin. Cancer Biol.
S1P induced changes in epithelial ovarian cancer proteolysis, invasion, and attachment are mediated by Gi and Rac
Gynecol. Oncol.
Association of promoter polymorphisms in MMP2 and TIMP2 with prostate cancer susceptibility in North India
Arch. Med. Res.
Cancer statistics
CA: Cancer J. Clin.
A novel biomarker for staging human prostate adenocarcinoma: overexpression of matriptase with concomitant loss of its inhibitor, hepatocyte growth factor activator inhibitor-1
Cancer Epidemiol. Biomarkers Prev.
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These authors contribute equally to this study.