Расторопши: семена ранней потенциальных
Preventive and Therapeutic implications of silibinin anti-metastatic efficacy
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- Conclusions and Future directions
Preventive and Therapeutic implications of silibinin anti-metastatic efficacySilibinin has a long history of human use and is devoid of side effects even when acute or chronic doses of silibinin are administered in animals and humans [56,68,69]. Various traditional toxicological tests have confirmed the non-toxic nature of silibinin and its safety profile [56,68]. In fact, rodent LD50 values for silibinin have never been achieved. Currently, close to dozen clinical trials are in progress examining the liver protective as well as other therapeutic benefits of silibinin. Now there are enough pre-clinical evidences that establish silibinin as an ‘antimetastatic agent’. These studies have shown that silibinin targets migratory/invasive and metastatic behavior of a wide-variety of cancer cells. Silibinin is reported to act through pleiotropic mechanisms including targeting of EMT-related events, inhibiting proteases expression and MAPK signaling, as well as adversely affecting the tumor microenvironment. These studies advocate greater use of silibinin in the clinical management of advanced metastatic stage of the disease. Silibinin could be potentially used as a preventing agent in patients diagnosed at early localized stage of the disease. Based upon its efficacy in pre-clinical studies, it is reasonable to expect that silibinin treatment would inhibit EMT in localized cancer cells, thereby prevent the metastatic progression of the disease. Since silibinin also possesses strong anti-angiogenic characteristics, it is expected to inhibit cancer growth but should also prevent the progression of micro-metastases that remain undiagnosed or under-diagnosed; thereby silibinin could prevent or delay the growth of metastatic lesions. Our completed pre-clinical studies have shown that silibinin is also effective against metastatic progression of cancer even when used as therapeutic agent; therefore silibinin should also be tested in clinic to treat advance stage of the cancer. In preventive studies, silibinin should be administered for a reasonable period of time before expecting a clinical outcome; however, in therapeutic settings, it should be administered through intravenous route to achieve a high systemic dose with the expectation that clinical outcomes could be measured in reasonably shorter duration. In this regard, it is important to emphasize here that the bioavailability of oral silibinin has been reasonably enhanced through its formulation with phosphatidylcholine and lately with nanoparticles. Intravenous injectable silibinin formulation (silibinin-Legalon) is already available and used recently against mushroom poisoning-related liver toxicity with successful outcomes, further suggesting that clinical benefits of silibinin against cancer metastasis should be exploited in near future. Conclusions and Future directionsMetastasis is a multistep and multifunctional biological event and is considered the final and most-life threatening stage of cancer progression. The high morbidity and mortality related to cancer metastasis are due to lack of effectiveness of current therapeutic regimes; alternatively, the use of nutraceutical agents has been suggested for the prevention and treatment of advance cancers. Nutraceutical agent silibinin has shown remarkable anti-metastatic efficacy against many cancers in various pre-clinical models. The anti-metastatic efficacy of silibinin has been reported through pleiotropic mechanisms including the inhibition of EMT in caner cells. However, more studies are still needed to further confirm the anti-EMT and anti-metastatic effect of silibinin in wide variety of human cancer cells under in vivo conditions. Furthermore, silibinin should be tested in the metastatic models, which more closely represent human metastatic disease condition. In future, there should also be greater emphasis on to understand the role of tumor microenvironment in metastasis initiation and progression as well as how silibinin affects these interactions. Overall, it is reasonable to anticipate that in the near future silibinin would be an important non-toxic nutraceutical agent in the management of metastatic cancers. Молекулярные механизмы ингибирования photocarcinogenesis, силимарин, фитохимических из расторопши пятнистой (Silybum marianum L. Gaertn.) (Обзор). Изменения в образе жизни за последние несколько десятилетий, в том числе большую часть времени Провел на свежем воздухе и использование автозагара устройств для косметических целей физических лиц, привели к росту заболеваемости солнечного ультрафиолетового (УФ) излучения-индуцированных кожных заболеваний, в том числе риск раковых заболеваний кожи. Солнечного УФ-излучения считаются наиболее распространенных канцерогенов окружающей среды и хронического воздействия на кожу УФ приводит к плоскоклеточного и базально-клеточного рака и меланомы в человеческой популяции. Различные фитохимические вещества, как сообщается, имеют существенные анти-канцерогенные деятельности, потому что их антиоксидантными и противовоспалительными свойствами. Силимарин - один из них и широко изучены для кожи свойствами возможностей. Силимарин, flavanolignan, добывается из плодов и семян расторопши (Silybum marianum L. Gaertn.), и было показано, что химические эффекты против photocarcinogenesis в мыши опухоль моделей. Местное лечение силимарин ингибирует photocarcinogenesis у мышей с точки зрения частоты опухолевых заболеваний, опухоли кратности и рост опухолей. Широкого спектра in vivo механистические исследования, проведенные в различных мышиных моделях показали, что силимарин обладает антиоксидантными, противовоспалительными и иммуномодулирующими свойствами, которые привели к предотвращению photocarcinogenesis в мышей. Данный обзор обобщает и обновляет свойствами потенциал силимарин с особым акцентом на его in vivo механизм действия. Предполагается, что силимарин может выгодно дополнить солнцезащитный крем защиты, и может быть полезно для лечения кожных заболеваний, связанных с солнечного УФ излучения-индуцированного воспаления, оксидативного стресса и иммуномодулирующим действием. Int J Oncol. 2010 May;36(5):1053-60. жүктеу/скачать 2.54 Mb. Достарыңызбен бөлісу:
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