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More recently, there has been a renewed push to identify natural remedies to fight prostate cancer.
Possible mechanisms of the anti-metastatic effects of the combination of luteolin (L), ellagic acid (E) and punicic acid (P) (L + E + P).
In 2013, another phase II clinical trial of PCa patients with rising PSA received 1 g (comparable to about 8 oz of PJ) or 3 g of PE daily for up to 18 months. Conflicts of InterestThe authors declare no conflict of interest.ReferencesAmerican Cancer Society. Europe’s drug regulator has approved the targeted melanoma drug Zelboraf (vemurafenib), expanding the treatment options available to nearly 160,000 people who are afflicted every year by the deadliest form of skin cancer. The European Medicines Agency’s approval of Zelboraf follows that of the United States Food and Drug Administration given in August, and Roche Holding AG, the drug’s Swiss maker, said it expects the European Commission to endorse the approval formally in February 2012.
The new medication is targeted for patients with tumors that have a mutation in a gene known as BRAF that allows melanoma cells to grow. Zelboraf is given as a twice-daily pill and is designed to be used alongside a companion diagnostic test, also from Roche, that identifies which patients have the BRAF genetic mutation. The European drugs watchdog said it backed Zelboraf for treating patients with the BRAF mutation who suffered from metastatic or unresectable melanoma—or melanoma that cannot be removed by surgery. Melanoma has a 90 percent survival rate when treated early, and because of its location on the skin’s surface, it is relatively easy to treat.
But melanoma’s invasive nature means that if left too long, it becomes highly aggressive: it can spread quickly to internal organs and the average survival rate is six to nine months. Only one-fourth of all people with metastatic or unresectable melanoma survive more than a year and less than 15 percent remain alive after five years. Thus, there is an urgent need for medicines to treat metastatic melanoma, which is also the sixth most common malignancy in men and seventh most common cancer in women. Related topics at this site; lung cancer and lung diseases, lung ailments and conditions, lung cancer photos, pictures and images, lung cancer signs, symptoms and prognosis. United Patients Group, the leading medical cannabis information and education site is dedicated to providing the most professional and safe resource for Medical Cannabis information.
Whether you have Cancer, Chronic Pain, MS, Arthritis or Anxiety, we are committed to helping you navigate this ever changing industry. Physicians can now learn about Medical Cannabis through our online CME courses in Cannabinoid Therapeutics. 5 of 88Cannabis Research - The Time is NowIt is well established that medical cannabis has been a successful treatment in the battle against cancer and dozens of other health conditions and diseases.
8 of 88Doctor, What Is The Dose Of My Cannabis Medicine?With the current information age, it is very easy to find dosing information for any drug online. 10 of 88UPG Kicks Off the Season of Giving By Spearheading Education and ResearchThis has been such an incredible year of growth and change for us here at United Patients Group. 14 of 88Could Cannabis Be a Safer Alternative to ADHD Drugs?As the school year gets underway, many children, teens, and college students will struggle with sitting in class and paying attention. 15 of 88The Entourage Effect: Why Whole Cannabis Is BetterWhether you smoke it, eat it, vaporize it, or ingest it as an oil, the medicinal cannabis you put in your body contains many chemicals that work together to make you feel better.
17 of 88The Role of the Nurse in Cannabis Dosing and AdministrationWith 23 states and the District of Columbia now allowing medical cannabis use, more and more patients are looking to cannabis as a treatment option. 19 of 88How Cannabis Helps LupusLupus is a chronic autoimmune disease in which your body can’t tell the difference between viruses, germs and bacteria and your body’s own healthy tissue. 20 of 88How Does Cannabis Help Menopause?Women of a certain age are all too familiar with the symptoms of menopause. 22 of 88"From Hospice to Healthy - Happy 82nd Birthday Dad!"Today marks yet another milestone for my father Stan Rutner – sometimes referred to as “The Miracle Man”. 27 of 88Hemp Utility Spans from Supplements to Batteries to BiofuelHemp is a remarkable plant that humans have used for thousands of years for everything from manufacturing to munchies to moisturizer to medicine. 28 of 88Cannabis Refugees: Why Anti-Marijuana Laws Are Uprooting LivesThe continued failure of the federal government to recognize the medicinal benefits of cannabis has created a refugee crisis. 29 of 88Why Nurses are Vital to the Medical Cannabis CommunityCannabis has been gaining momentum as a viable and safe medical treatment over the last several years.
34 of 88Salicinium: A Homeopathic Cancer Treatment Method that Tricks Cancer CellsIn order to understand what salicinium does, you need to know how cancer cells operate. 35 of 88Enzymes and Cancer: An Alternative Treatment Worth Exploring?Here at United Patients Group, we are always searching for alternative treatments that can augment or supplement mainstream cancer treatments.
36 of 88New Research Shows Essential Oils Can Kill Cancer CellsChinese researchers tested ten essential oils against three kinds of tumors.
38 of 88Doctors Weigh In - Medical Cannabis Dosing: Why Less May Be MoreMany medical cannabis patients take an overly aggressive approach to treatment. 39 of 88At Least One Issue Has Bipartisan Support: MarijuanaPolitical polarization has been a major obstacle to Congress getting anything done for years now. 40 of 88Do You Know the Difference Between Ketogenic and Alkaline Diets?At UPG, we get a lot of questions about diets and how they could benefit people living with serious ailments. 42 of 88Are Cannabinoids as Effective as Albuterol for Treating Asthma?Ongoing research is proving cannabis-based medications effective for safely treating a wide spectrum of medical conditions. 43 of 88Don't Judge Your Strain by Its NameThey say you shouldn’t judge a book by its cover, but there’s not a lot of harm if you do—maybe you buy a boring book. 44 of 88Fighting Obesity and Diabetes with CannabisAlthough obesity is more prevalent in some demographics, it is lower in others—including regular users of cannabis. 45 of 88Cannabis Suppositories: Is the Posterior Superior?Suppositories are often the butt of many jokes and puns, but rectal administration of marijuana has many advantages. 46 of 88Is Cannabis the Solution to the Antibiotic-Resistant Staph and Superbug Crisis?In the United States, (MRSA) kills about 18,000 of the 94,000 people it infects each year.
47 of 88Is Cannabis a Gateway Drug or an Exit Drug?As we prepare to end the year, many people are thinking about which healthy changes they want to make in the new year. 48 of 88Continue Your Cannabis Education with United Patients GroupWe are thrilled to announce that United Patients Group is now offering online courses on a number of medical-cannabis-related topics. 50 of 88Fighting Depression Using Cannabis: Research shows less is more!The holiday season can be stressful for everyone. 51 of 88What Is Homeostasis and How Can Cannabis Help?We wish to thank everyone who attended our first cannabis patient conference, Medical Cannabis: The Science Behind the Hype.
53 of 88Top 5 Terpenes that Amplify the Healing Power of CannabisUnlike cannabinoids, terpenes are found in many plants; they’re the chemicals that give a plant its aroma and flavor. 55 of 88Why United Patients Group is considered, "The Virtual Hand of the Medical Marijuana Industry."We are often asked what we do for patients here at United Patients Group. 57 of 88Fibromyalgia: Big Pharma vs Medical CannabisThe estimated five million Americans coping with fibromyalgia are not use to hearing good news. 58 of 88How Cannabis Helps with Bipolar DisorderWhen we talk about the benefits of medical cannabis, we tend to focus on physical disorders: cancer, glaucoma, multiple sclerosis, etc. 59 of 88Should the Federal Government and FDA Be Sued for Murder?The federal government is allowing sick people to die when it knows that cannabis could save them. 60 of 88Why Decriminalization isn't Good EnoughTo say, “We have won once the Country decriminalizes cannabis,” would be to neglect her greater call.
61 of 88Cannabis Is More Than Skin DeepYou may have heard that your skin is your largest organ, and this is true.
68 of 88Surprising New Cancer Killer: FrankincenseMost people associate frankincense with the story of the three wise men who visited the baby Jesus in Bethlehem. 70 of 88Heal Dental Problems Naturally with Oil PullingHere at United Patients Group, we’re always on the lookout for natural alternatives.
71 of 88Cannabis Infused Coconut Oil - How to and the benefits!Coconut oil has been growing in popularity among various groups of people for a while now. 73 of 88By Endorsing High-CBD Cannabis, New Legislation Will Do More Harm than GoodWord is out about the benefits of high-CBD medical cannabis.
74 of 88To Tell or Not To Tell?One question I come across often is “Should I tell my doctor?” My answer-it depends. 76 of 88United Patients Group - Seal of ApprovalWhat is a Seal of Approval and How Can I Get Approved?
77 of 88The Interesting Rise of Seniors within Medical MarijuanaMarijuana has been stereotypically associated with a younger crowd.
78 of 88Drug Testing 101Ronald Reagan passed an Executive Order in 1986 that mandated federal workers be drug-free on and off the job.
79 of 88Vitamin D and Breast CancerVitamin D regulates the flow of calcium into the bloodstream and is essential for normal bone development. 80 of 88Medical Marijuana: 10 Health Benefits That Legitimize LegalizationPrescription drugs kill about 100,000 people in the world each year.
83 of 88Medical Marijuana and Lyme Disease - Alexis' storyUnited Patients Group is happy to be here for all types of patients.


84 of 88Juicing For Life - Health Conditions and JuicingJuicing is the latest manifestation of a centuries-old health practice.
85 of 88Debunking MMJ DemographicsDespite society’s latest increase in approval over marijuana usage, stereotyping of marijuana users still exists. 86 of 88Field Guide to Marijuana and the WorkplaceSince the November election, we have been keeping a close eye on the legal status of medical and recreational-use marijuana. 87 of 88Naturopathic Medicine Naturopathic Medicine is a unique and distinct system of health care that emphasizes the use of prevention and natural therapeutics. 88 of 88How Cannabis Affects the BrainHumans have been smoking marijuana for nearly 5,000 years and it has been used to treat a whole range of different ailments and illnesses.
Men with early stage prostate cancer have several treatment options available to them including watchful waiting surgery and radiation therapy. Among men treated for prostate cancer those who received radiation therapy were more likely to develop bladder or rectal cancer according to a new study from the University of Michigan Comprehensive Cancer Center. Since its first isolation and identification in 1989, Hepatitis C virus (HCV), has caused significant disease burden to humans worldwide. Here, researchers at the University of Massachusetts Medical School found that the HCV virus can utilize host exosomes to transmit infection to naive liver cells, even in the presence of potent blocking anti-HCV receptor antibody treatments.
Exosomes are cell-derived vesicles that are present in many and perhaps all biological fluids, including blood, urine, and cultured medium of cell cultures.
In fact, their doctors give them drugs to get rid of the hormone because it can fuel the growth of breast cancer.
In a study presented at the 31st annual San Antonio Breast Cancer Symposium, he showed that for about a third of the 66 participants — women with metastatic breast cancer that had developed resistance to standard estrogen-lowering therapy — a daily dose of estrogen could stop the growth of their tumors or even cause them to shrink. Ellis believes that estrogen therapy offers an appealing alternative to chemotherapy for metastatic breast cancer that has become resistant to estrogen-lowering agents called aromatase inhibitors, such as exemestane, anastrazole and letrozole.
These drugs deplete the body of estrogen and are standard treatments for hormone-receptor positive breast cancers, which account for about 75 percent of breast cancer cases. IntroductionProstate cancer (PCa) is the second-leading cause of cancer-related deaths in men in the United States.
The current treatments include surgery, radiation, chemotherapy, androgen-deprivation therapy (ADT), immunotherapy, and targeted therapy. Possible mechanisms include increasing cell adhesion, decreasing cell migration and C–X–C motif chemokine 12 (CXCL12) chemotaxis, targeting hyaluronan and arachidonic acid pathway, and reducing matrix metalloproteinases (MMPs) production.
Inhibition of Matrix Metalloproteinases (MMPs)The association of matrix proteolysis and cancer has long been demonstrated, and destruction of the basement membrane, an ECM structure that underlies epithelia, is a well-established hallmark of malignant invasion [42,43] (Figure 3). Possible mechanisms include increasing cell adhesion, decreasing cell migration and CXCL12 chemotaxis, inhibiting proliferation, inhibiting angiogenesis, and inhibiting epithelial-mesenchymal transition (EMT). Every year, around 60,000 people are affected by this cancer, and 15,000 people die from it.
Experts Say No.The idea behind cannabis testing is to keep patients safe from contaminants. Gupta, "California Has Been a Refuge for Cannabis Patients for Nearly Two Decades"California has been a refuge for cannabis patients for eighteen years. Sanjay Gupta Sets Record Straight on CannabisWhen one of America’s most trusted and prominent doctors changed his stance in favor of marijuana last month, we at United Patients Group did a collective back-flip.
Manystudies have suggested that Saw Palmetto could help maintain prostate health with relatively few side Prostate Cancer Symptoms Fever effects*. Support what is prostate infection treatment proper urinary function with Ultimate Prostate Formula which contains saw palmetto shown to support prostate and urinary health.* Prostate problems increase as men reach age 40 and older but younger Prostate Cancer Symptoms Fever men are nt Prostate Cancer Symptoms Fever immune to unhealthy prostate glands.
At the moment the common screening for prostate cancer is through a digital rectal exam ultrasound exam or PSA (Prostate-specific antigen) blood test. So far, there is no vaccine against HCV, and neutralizing antibody therapies to block receptor–mediated transmission of HCV to liver cells have so far achieved limited therapeutic benefits.
Additionally, we identified alternative treatment strategies that can block host exosomes from transmitting HCV infection. Exosomes contain various molecular constituents of their cell of origin, including proteins and RNA.
Louis — he has demonstrated that estrogen therapy can help control metastatic breast cancer. All material provided on this website is provided for informational or educational purposes only. Pomegranate fruit from the tree Punica granatum has been used for centuries for medicinal purposes and is described as “nature’s power fruit”. The American Cancer Society has estimated that a total of 233,000 new cases will be diagnosed and 29,480 men will die of PCa in 2014 [1]. The pomegranate fruit is derived from the tree Punica granatum, is edible and is cultivated in Mediterranean countries, Afghanistan, India, China, Japan, Russia, and some parts of the United States [10,11]. MMPs are a family of highly homologous Zn2+ endopeptidases that collectively cleave extracellular matrix (ECM) molecules [44].
The prostate cancer by age statistics management of early-stage prostate cancer remains controversial especially for tumours detected with PSA testing.[12] The existing evidence is A decision to use this technique takes into account several prognostic factors including Gleason score PSA level and TNM classification. HIFU prostate cancer treatment is the latest alternative for men with unifocal or independent prostate cancer. 100% of all proceeds we raise from our events and raffles go to the Prostate Cancer Foundation.
The safety of Viadur (leuprolide acetate implant) was evaluated in 131 patients with prostate cancer treated for up to 24 months in two clinical if prostate cancer metastasis trials. Surgery (radical prostatectomy): An incision is made in the lower abdomen or through the perneum (between the anus and the scrotum) and the prostate is This technique was developed as an alternative to surgery for patients who have recurrent cancer in the prostate after radiation treatments. This study provides novel insights to an alternative mechanism of HCV transmission that can compromise anti-HCV immune therapies and proposes potential therapeutic approaches to block exosome-mediated transmission of HCV infection.
It is becoming increasingly clear that exosomes have specialized functions and play a key role in, for example, coagulation, intercellular signaling, and waste management. Numerous studies have supported a role for MMPs in tumor invasion and metastasis [45,46,47]. The statistically significant prolongation of PSA doubling time and the lack of metastatic progression in any of the patients in both of these studies, strongly suggests the potential of PJ for treatment of PCa.Although extremely promising, a major drawback of these two clinical trials was the absence of a proper placebo control group. Men run the risk of testicular hrinkage reduced lower back pain prostate problems sperm count impotence baldness and enlarged prostate. The treatments for prostate cancer including surgery and radiation can result in serious life-changing side effects including imotence and incontinence as well as more critical complications including death. The Prostate Cancer Treatment Guide lists treatment descriptions survival hematuria in prostate cancer rates side effects and other important information associated with prostate cancer.
This report provides elemental information and data relating to the clinical trials on Hormone-Sensitive Prostate Cancer. Evidence suggests that small host extracellular vesicles (exosomes) can mediate receptor-independent transfer of genetic material between cells, though their role in HCV transmission remains uncertain. They possess strong antioxidant, anti-inflammatory, anti-atherogenic effects, and some studies have suggested that they also may have anti-tumorigenic properties [12,13,14,15]. It has previously been shown that arachidonic acid (AA) turnover can be an indicator of invasiveness and metastasis [31]. MMPs-2, -7, -9 and -11 have all been shown to contribute to tumor progression in studies using MMP-deficient mice [48]. A recent randomized double blind study showed that men with PCa prior to radical prostatectomy were given PE daily for up to 4 weeks. Patients who develop t-NEPC have an aggressive clinical course often develop visceral or lytic bone metastases responds only transiently to One of them that has been shown to block DHT is saw palmetto extract. I was hoping he would be in Stage I so they could either treat it with the wait and see approach or radiation therapy.
More recently, we have shown that three components of PJ, luteolin, ellagic acid and punicic acid together, have similar inhibitory effects on prostate cancer growth, angiogenesis and metastasis. In fact, the antioxidant activity of pomegranates has been shown to be higher than that of red wine or green tea, two dietary substances that are showing promise in preclinical prostate cancer models and in patients with PCa [16].
The rate of AA turnover in prostate tumor cells is 10-fold higher than its rate in the surrounding normal cells [32]. Other studies have shown that MMP-9 was exclusively expressed by malignant prostate tissue and, in particular, by tumors that exhibit aggressive and metastatic phenotypes [49,50]. Men on dutasteride had a 23% overall lower risk of being diagnosed with biopsy detectable prostate cancer when compared to men on placebo due to a It is found in low levels in normal men and is not elevated with other forms of cancer. Saw palmetto, botanically known as Serenoa repens or as sabal palm in Europe, is a magnificent palm An excess of DHT is believed one of the primary causes of prostate problems as well as the cause of Maximum urinary flow was significantly higher in the treatment group compared to the placebo Prostate cancer usually occurs in older men.
However, over time, the cancer develops ways to bypass hormone dependence, becoming highly aggressive, castration-resistant prostate cancer (CRPC) that metastasizes to the lung, liver and bone [2,3].


In this review we discuss data on the effects of PJ and PE on PCa cells in cell culture, in animal models and in clinical trials as well as specific components of the pomegranate fruit and how they have been used to study the mechanisms involved in prostate cancer progression. AA is released from membrane phospholipids by phospholipase A2 (PLA2) and is metabolized into prostaglandins and thromboxanes via the cyclooxygenase (COX) system [33]. It has also been shown that inhibitors of both PLA2 and COX were able to reduce the production of MMP-2 from PCa cells, indicating that the anti-invasive effect of blocking AA metabolism through the COX pathway is associated with the inhibition of MMPs in tumor progression [41].
The level of 8-hydroxy-2-deoxyguanosine (8-OHdG), an oxidative stress biomarker, was compared between patients in treatment and placebo group.
In addition to the hormone ablation, chemotherapy is available today to treat CRPC, but it is not very effective because PCa cells divide slowly and, like with prostatectomy, the treatments are aggressive and have many side effects [4]. PE lowered the level of 8-OHdG but the difference was not statistically significant, suggesting the need for larger and longer studies in the future [103].More recently, results from a double-blind, placebo-controlled randomized trial using an oral capsule containing a blend of pomegranate, green tea, broccoli and turmeric showed that the supplement delayed PCa progression as indicated by slower increases in PSA levels. We also discuss the effects of specific components of the pomegranate fruit and how they have been used to study the mechanisms involved in prostate cancer progression and their potential to be used in deterring prostate cancer metastasis.
FDA approved sipuleucel-T (Provenge®) is an autologous cellular immunotherapy to treat metastatic PCa. HA is frequently localized in the stroma of solid tumors, facilitating cell migration, tumor invasion and metastasis [56,57].
In the clinical trial on which this approval was granted, the median overall survival rate of patients who received sipuleucel-T improved by only 4.5 months. Also, the expression of cytosolic PLA2 was increased in androgen-independent PCa cells [39,40]. HA interacts with cell surfaces through binding to specific cell-surface receptors, such as hyaluronan-mediated motility receptor (HMMR), to induce the transduction of a range of intracellular signals leading to numerous cellular responses, including those that involve tyrosine kinases, protein kinase C, focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinase, nuclear factor-?B and RAS, as well as cytoskeletal components [58]. In addition, inhibitors which selectively inhibit PLA2 or COX in the prostaglandin synthesis pathway were capable of inhibiting human PCa cell invasion [41]. Previous studies have revealed that the expression level of HMMR was highly stimulated in CRPC cells [59,60,61]. Novel androgen receptor (AR) antagonists such as enzalutamide (Xtandi®) and androgen biosynthesis inhibitors such as abiraterone (Zytiga®), have shown great promise as androgen deprivation therapies to prolong overall survival rate among patients with metastatic PCa [6,7]. These results suggest that AA metabolism plays a role in human PCa cell invasion and implicates the involvement of PLA2 and COX in a specific invasion associated signal cascade. A study using microarray analysis of gene profiles in prostate epithelium obtained from 50 PCa patients showed that major components of the HMMR signaling pathway, such as RhoA-activated kinase (ROK), were consistently overexpressed in metastatic PCa cells [60]. Another novel drug, Cabozantinib, is a potent dual inhibitor of the tyrosine kinases c-MET and vascular endothelial growth factor receptor 2 (VEGFR2), and has been shown to reduce or stabilize metastatic bone lesions in CRPC patients [8,9]. Furthermore, it has been shown that PE significantly reduced the expression level of PLA2 in PC3 cells [30].
Recently, we showed that PJ or a combination of its components luteolin (L), ellagic acid (E) and punicic acid (P) decreased cell migration, which is an important cellular process in metastasis of PC3 cells, and the inhibitory effect was mediated via down-regulating the expression of HMMR [23,62]. Chemotherapy and targeted therapies: Are we making progress in castrate-resistant prostate cancer?
Taken together these findings suggest that PE may suppress PCa cell invasion through blocking the AA metabolism pathway. Therefore, these findings suggest that the anti-metastatic effect of PJ and of L + E + P also occur via targeting HA signaling pathways in PCa cells. Specific Components of Pomegranate with Known Effects on PCaThe pomegranate fruit can be divided into three major anatomical components: the juice, the pericarp and the seeds. These discrete components of the pomegranate fruit have been found to exert anti-proliferative and anti-invasive effects on PCa cells [30]. The juice and pericarp contain a rich complement of two types of polyphenolic components which have attracted interest for recent research: anthocyanins which give the juice its red color [74], such as delphinidin, cyanidin and pelargonidin, and hydrolyzable tannins, such as the punicalagin and gallagic acid [13,75,76]. In Vivo EvidencePromising evidence also come from in vivo studies using mouse xenograft tumor models. Other polyphenolic components of possible interest include kaempferol, quercetin and luteolin [75,77,78]. In these studies, human PCa cells were transplanted, either subcutaneously or orthotopically, into immunocompromised mice that do not reject human cells.
The seed oil, which is comprised of 65%–80% conjugated fatty acids, also contains many compounds of interest with known antioxidant and anti-cancer activities [79].
Oral administration of ellagitannin-enriched PE not only inhibited LAPC4 xenograft tumor growth in SCID mice [84] but also inhibited tumor-associated angiogenesis [85]. Mouse LAPC4 xenograft tumors are initially androgen-dependent and respond to castration but subsequently become androgen-independent after several weeks [27].
Ellagic acid was shown to possess anti-tumorigenic activities on lung, cervical, colon, breast and prostate cancer cells [86,87,88]. Cabozantinib (xl184), a novel met and vegfr2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Recently it was shown that ellagic acid and its metabolite urolithin A synergistically inhibited cell growth and induced apoptosis in DU145 and PC3 cells [89]. Another advantage of transgenic models is that mice are immunocompetent, hence the tumor microenvironment can be more accurately simulated. It has recently been found that PE inhibits tumor growth in a transgenic adenocarcinoma mouse prostate (TRAMP) model [29]. Using a Matrigel invasion assay, it was shown that luteolin inhibits invasion of PC3 cells via increasing the expression of E-cadherin [93]. TRAMP mice were fed orally with two doses of PE, equivalent to 250 and 500 mL of PJ, and examined for tumor growth [29]. It is established that decreased expression of E-cadherin, one important cell-cell adhesion molecule [94,95], results in a loss of cell-cell adhesion and increased cell invasion [96]. These investigators found that PE not only inhibited tumor growth but also enhanced the overall survival of the treated mice. It was found that luteolin increased the expression of E-cadherin, and that knockdown of E-cadherin reversed the effect of luteolin on invasion of PC3 cells; in addition, intraperitoneal administration of luteolin three times a week reduced lung metastasis of PC3 xenograft tumors in nude mice [93].
Cabozantinib in patients with advanced prostate cancer: Results of a phase II randomized discontinuation trial.
In addition, luteolin has been shown to inhibit PCa tumor growth via targeting angiogenesis. After primary xenograft PC3 tumors have developed in nude mice, it was found that intraperitoneal administration of luteolin for 16 days not only inhibited tumor growth, but also reduced the number of blood vessels in the tumor [97].Punicic acid, the major component of pomegranate seed oil (70%–80%), has been shown to possess anti-cancer effects on PCa. Possible mechanisms of the effects of pomegranate on PCa tumor growth are summarized in Figure 2.
It inhibits cell growth of androgen-dependent LNCaP cells stimulated by DHT and inhibited DHT-stimulated androgen receptor nuclear accumulation as well as the expression of androgen receptor-dependent genes [81]. These investigators also found that punicic acid induced apoptosis via a caspase-dependent pathway in LNCaP cells.Recently, we showed that luteolin (L), ellagic acid (E) and punicic acid (P), individually and in combination, additively affect processes important for metastasis.
L + E + P in equal amounts inhibits the growth of hormone-dependent and -independent PCa cells, their migration and their chemotaxis towards CXCL12, a factor that is important in PCa metastasis [62]. The combination of these components also increases the expression of cell adhesion genes and decreases expression of genes involved in cell cycle control and cell migration.
We have also shown similar anti-metastatic effects of L + E + P on breast cancer cells [98].Based on these results in cell culture, we investigated whether L + E + P inhibits PCa metastasis in vivo.
We used a SCID mouse model in which luciferase-expressing human PCa cells were injected ectopically in the region of the prostate. One advantage of this model is that tumor growth and metastasis can be monitored by bioluminescence imaging. We found that L + E + P significantly inhibited PC-3M-luc primary tumor growth and that none of the tumors treated with L + E + P metastasized. One disadvantage of using this model to study metastasis is the relative low metastasis incidence in untreated mice.
Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. We also showed that L + E + P decreased human endothelial cell migration and adhesion, disrupted endothelial tube formation and inhibited the production of the angiogenic factors IL-8 or VEGF by the tumors [100]. The possible mechanisms of the anti-metastatic effects of L + E + P are summarized in Figure 4. Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer.
Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer.



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