Расторопши: семена ранней потенциальных
СИЛИБИНИН ОБЛАДАЕТ СИЛЬНЫМ АНТИ-АНГИОГЕННЫХ ЭФФЕКТИВНОСТЬ ПРОТИВ РАКОВЫХ КЛЕТОК ПРЕДСТАТЕЛЬНОЙ
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- Бұл бет үшін навигация:
- Выводы
- PROSTATE CANCER CHEMOPREVENTION
СИЛИБИНИН ОБЛАДАЕТ СИЛЬНЫМ АНТИ-АНГИОГЕННЫХ ЭФФЕКТИВНОСТЬ ПРОТИВ РАКОВЫХ КЛЕТОК ПРЕДСТАТЕЛЬНОЙТаргетинг ангиогенеза считается важным элементом в предотвращении роста и прогрессии солидных опухолей, включая рак простаты. Силибинин сообщили ингибируют ангиогенез, снижение уровней экспрессии VEGF и опухоли плотности микрососудов в опухоли простаты (107,108,116). Это анти-ангиогенный потенциал был поддержан в исследовании мышей TRAMP где силибинин кормления привело к снижению экспрессии platelet endothelial cell adhesion molecule-1 (PECAM1)/CD-31, VEGF, VEGFR2, HIF-1α, и iNOS (117). Это выражение pattern соответствовало увеличение глюкозы и цитрата использовать вместе с сопутствующими снижение лактата, холестерина и фосфатидилхолина уровней предстательной железы опухоли силибинин кормили мышей TRAMP (128). Силибинин лечение LNCaP и PC3 простаты раковых клеток, подавляет их синтез HIF-1α как исходно, а также индуцированного гипоксией (129). ВыводыСилибинин, флавоноид антиоксидант, полученный из молочного чертополоха используется в течение тысячелетий для лечения различных недугов. В более поздние времена, как продукт длительного исторического использования и вышеупомянутые антиоксидант химии наряду с защитными свойствами выявлены в ряде других флавоноидов, силибинин исследована в ряде моделей рака. В этих исследованиях, силибинин был обнаружен и изъят многофакторного анти-рак эффективности, действующих на широкий спектр сигнальных и регуляторных механизмов в различных условиях. Особенно в отношении рака простаты, силибинин было показано, что изменения клеточной пролиферации, апоптоза, EMT, инвазия, метастазирование и ангиогенез. Эти эффекты силибинин имеют потенциал для воздействия на прогрессирование рака простаты, охватывающей полный спектр клиническим проявлением заболевания от начальных клеточных дисфункций в зачаточном поражений до продвинутого метастатических опухолей. Однако, дальнейшие исследования, чтобы подтвердить механизмов силибинин влияние на рак простаты микроокружения, а также для выяснения его эффективной доставки и клинического использования все еще необходимы. В совокупности данные, обеспечивает сильную поддержку обещание силибинин в качестве кандидата предстательной железы химические агента. PROSTATE CANCER CHEMOPREVENTIONCancer chemoprevention is a treatment regime centered on the use of chemical agents to reduce cancer risk. These agents may be derived either synthetically or from natural products and are intended for long-term use, generally limiting candidate agents to nontoxic compounds. The rationale for this modality is based on the multistage and often lengthy period of time required to accumulate the cellular damage necessary for carcinogenesis (i.e., dysfunctional proliferation, differentiation, apoptosis, etc.). This then provides an opportunity to inhibit or eliminate initiated cells or localized lesions prior to their development into a fully malignant tumor. This general concept of cancer chemoprevention can be subdivided into primary, secondary, and tertiary cancer chemoprevention depending on the stage of carcinogenesis that is being targeted. Primary chemoprevention focuses on the removal of the initiating cellular dysfunction/s to decrease or eliminate cancer incidence prior to cancer formation. This is an ideal clinical outcome as it has the greatest impact on reducing treatment costs, adverse effects to the patient, and ultimately, mortality due to cancer. Barring this outcome and premalignant lesions already formed, secondary chemoprevention seeks their arrest or elimination, thus slowing or reversing progression of these lesions into malignant ones. Finally, if the previous interventions have not or cannot be enacted and a primary tumor has formed, tertiary chemoprevention seeks to inhibit the progression of tumor into a metastatic cancer as well as to prevent the recurrence of this tumor if it has been treated. In short, a cancer chemoprevention strategy could be applicable to almost all stages of carcinogenesis including post-therapy. Prostate cancer is well suited for a cancer chemoprevention scheme for several reasons. One reason is the number of people afflicted by this disease. It is the most common cancer diagnosed in men in the United States, and there were approximately 241,740 new prostate cancer cases in 2012 alone (1). As a result, prostate cancer is also the second leading cause of mortality with an estimated 28,170 deaths in 2012 (1). Prostate cancer, when detected in advanced and metastatic stage, results in high mortality with almost three fourths of those diagnosed dying within 5 years; however, advances in early detection have resulted in an increase in the treatment of prostate cancer as early and localized disease (1). But the counted success of early detection serves as a double-edged sword as it also comes with a concomitant increase in aggressive intervention where less aggressive treatment might have better served the patient. This is the second factor making prostate cancer a candidate for chemoprevention, situations where adverse side-effects develop in patients as a consequence of treating prostate cancer especially in cases where perhaps they were not necessary. There are a host of treatment options, and each to varying degrees carries the risk of adverse effects. Among these, the principle risks are urinary incontinence, bowel issues, and impotence. In one study, normalized by only reporting patients with normal function prior to treatment, upwards of 58% of patients reported minor to major urinary dysfunction and 27% reported bowel problems 3 years following radical prostatectomy (2). In addition, a whopping 94% reported some sexual dysfunction of which two thirds of these were reported as severe issues. In another study following the effects of radical prostatectomy 2 years following treatment, almost 49% of patients reported urinary issues ranging from complete lack of control to frequent or occasional leakage (3). Similarly, 60% of patients reported severe sexual dysfunction (3). In patients treated with radiation, it was found that urinary issues were only reported in 17% of cases but bowel issues increased in number to 66% of patients and sexual dysfunction remained high at 74% reporting mild or major issues 3 years following treatment (2). Finally, the enormous cost of treating prostate cancer highlights the benefits of the chemoprevention approach. In the USA, an estimated 11.85 billion dollars were spent in 2010 on direct health care costs alone (4). This cost is predicted to grow as a combination of increasing cancer incidence, improved early diagnosis, increasing life expectancy, and higher priced treatments gaining acceptance. In fact, this last factor is estimated to have increased prostate cancer health care costs by more than 350 million dollars from just 2002 to 2005 (5). As this sum only reflects the direct health care costs, it does not include lost worker productivity due to infirmity or death. In addition, the stress of diagnosis (whether it is accurate or a false positive) and the fear of disease recurrence place a heavy burden on the mental well-being of the patient. For these reasons, chemoprevention whereby prostate cancer might be prevented from developing or at least from progressing to a symptomatic level would be ideal to aid in lowering these costs while improving the quality of life of a large number of potential sufferers. As there is such a clear benefit in reducing the burden of prostate cancer, both societal as well as individual, several classes of agents have been brought forth as potential chemopreventive agents. One agent of interest is finasteride, a synthetic type II 5-α-reductase (5αR) inhibitor used in the treatment of male pattern baldness. The mechanism of action of 5αR is to inhibit androgen receptor (AR) induced signaling by inhibiting the conversion of testosterone into dihydrotestosterone, a higher affinity ligand of AR. As androgen-AR signaling is an important factor in the development and progression of prostate cancer, this activity has the potential to reduce or reverse the development of the disease. In a large-scale study, finasteride was shown to reduce incidence of prostate cancer, but consistent with the long-term response of prostate cancers to other AR-ablating compounds, the tumors that did arise despite finasteride treatment more frequently had high Gleason scores, which is associated with high mortality (6,7). Other potential chemopreventive compounds have been derived from natural products often identified based on their historic usage and more specifically food products based partially on ease of clinical translation. Green tea is one such product, its active ingredient believed to be a mixture of catechins (polyphenols with antioxidant properties), most commonly derived from the plant Camellia sinensis (8,9). Green tea has been associated with decreased overall risk of cancer and a high intake was found to be associated with a lower incidence of prostate cancer in men (9,10). Oral administration of green tea catechins reduced PSA levels (9). Another natural product, soy, contains a mixture of isoflavones exerting antioxidant properties. Soy consumption has been associated with a decreased risk of prostate cancer (11), which might be a result of reported inhibition of signaling pathways including AR, Akt, NF-κB, mitogen-activated protein kinases (MAPKs), and Notch signaling (12,13). The tomato (Solanum lycopersicum) contains a compound called lycopene which is a carotenoid with strong antioxidant property. Elevated lycopene consumption is associated with low prostate cancer risk (10,14). Another fruit, pomegranate (Punica granatum) contains a mixture of polyphenolic compounds that act as antioxidants which have been shown to delay prostate cancer growth in patients diagnosed with prostate cancer (15). A specific polyphenolic antioxidant agent that has been extensively studied for its chemopreventive properties is silibinin. жүктеу/скачать 2.54 Mb. Достарыңызбен бөлісу:
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