Розмарин и рак Rosmarinus officinalis & cancer Научные исследования
Evaluation of anti-cancer and immunomodulatory effects of carnosol in a Balb/c WEHI-164 fibrosarcoma model
жүктеу/скачать 2.03 Mb.
|
- Бұл бет үшін навигация:
- Author information
- Carnosol , радиационной и меланомы: трансляционные возможности.
- Результаты
- Carnosol, radiation and melanoma: a translational possibility.
- CONCLUSIONS
Evaluation of anti-cancer and immunomodulatory effects of carnosol in a Balb/c WEHI-164 fibrosarcoma model.Rahnama M1, Mahmoudi M, Zamani Taghizadeh Rabe S, Balali-Mood M, Karimi G, Tabasi N, Riahi-Zanjani B. Author information
AbstractAbstract Agents that destroy tumor cells and simultaneously boost host anti-tumor immunity are of keen interest in cancer therapy. In the present study, the effect of carnosol on anti-tumor immunity in a Balb/c mouse model of fibrosarcoma was evaluated. Carnosol was administered intraperitoneally daily (at 5 or 10 mg/kg/day, for 7 days) to tumor-bearing mice (i.e. 7 days after initial injection of tumor cells). Another group of tumor-bearing mice was treated with 20 mg cyclophosphamide/kg/d (positive control); a final group received vehicle only (vehicle control). After an initial measure on Day 0, tumor size was measured twice during the 7-day treatment period. One day after the final treatment with vehicle/carnosol (i.e. Day 7), the mice had their tumors measured and then were euthanized to permit their spleen and tumor to be harvested for isolation of, respectively, splenocytes and tumor-associated lymphocytes. Using these materials, spontaneous and mitogen-induced release of interleukin (IL)-4, IL-10, and interferon (IFN)-γ, lymphocyte proliferation, and the absolute numbers/relative percentages of splenic and tumor-associated T-regulatory (Treg) and other T-lymphocyte sub-sets were evaluated. The results showed that carnosol at both doses significantly suppressed tumor growth and caused depletion of splenic and tumor-associated Treg cells. It also caused relative (vs control mouse cell values) decreases in splenocyte spontaneous/inducible production of IL-4 and IL-10 and increases in IFNγ and cell proliferation. Carnosol at either dose did not cause changes in the percentages of CD4+ or CD8+ lymphocytes in the spleen or in tumor-associated lymphocyte populations. The observed increases in IFNγ, decreases in IL-10 and IL-4 production, and reductions in splenic/tumor-associated Treg cell levels might be signs reflecting the potential anti-tumor activity of carnosol. Based on the findings here, it is asserted that carnosol is a likely candidate - after more complete toxicologic evaluation - for eventual use as an anti-cancer therapeutic. Carnosol, радиационной и меланомы: трансляционные возможности.Сравнить генозащитных и радиопротекторное действие carnosol (COL) от повреждений, индуцированных ионизирующим излучением с аналогичными влияния различных антиоксидантных соединений. Методы:В генозащитных эффект был изучен с помощью данного теста для антимутагенная активность, в которой снижение частоты микроядер была оценена в цитокинез-блокированных клеток лимфоцитов человека. Радиопротекторный эффекты исследовали жизнеспособность клеток тест (МТТ) в PNT2 (нормальной простаты) и B16F10 (меланомы) клеточных линий, когда они вводили перед воздействием различных X-ray дозах (4, 6, 8, 10 и 0 гр). Результаты:Carnosol показывает значительное генозащитных мощность (p < 0,001) против излучения с фактором защиты 50 %, и снижению доз облучения фактор 4.3. Выживаемость клеток, полученных с COL, вводят до облучения 10 гр рентген показал фактором защиты 55,1 %, исключая 39 % радиационно-индуцированной гибели клеток в нормальных эпителиальных клетках простаты (PNT2) (p < 0,001). Однако, в клеточных линиях меланомы (B16F10) проанализированы, COL действовал не в качестве радиопротектора, но в качестве сенсибилизирующего агента повышение клеточной смерти на 34 % (p < 0,01) и производить аксессуар отношение 2.12. Выводы:Carnosol могут быть разработаны в качестве радиопротектора в опухолевых клетках. Однако, в B10F16 клетках меланомы, процесс меланогенеза активируется COL ведущих к перераспределению ферментативной остатки глутатиона и цистеина-лиазы производства, которые могли бы нарушить внутриклеточные окислительно-восстановительные системы обороны. Этот эффект проявляется как увеличение мощности ионизирующего излучения-индуцированного повреждения, и, таким образом, демонстрирует парадоксальное защитный эффект COL на клетках меланомы. Clin Transl Oncol. 2013 Sep;15(9):712-9. doi: 10.1007/s12094-012-0994-9. Epub 2013 Jan 29. Carnosol, radiation and melanoma: a translational possibility.Alcaraz M1, Achel DG, Olivares A, Olmos E, Alcaraz-Saura M, Castillo J.
To compare the genoprotective and radioprotective effect of carnosol (COL) against damage induced by ionizing radiation with similar effects produced by different antioxidant compounds. METHODS:The genoprotective effect was studied by means of the micronucleus test for antimutagenic activity in which the reduction in the frequency of micronuclei was evaluated in cytokinesis-blocked cells of human lymphocytes. The radioprotective effects were studied by cell viability test (MTT) in PNT2 (normal prostate) and B16F10 (melanoma) cell lines when they were administered before exposure to different X-ray doses (4, 6, 8, 10 and 0 Gy). RESULTS:Carnosol shows a significant genoprotective capacity (p < 0.001) against radiation with a protection factor of 50 %, and a dose-reduction factor of 4.3. Cell survival obtained with COL administered before exposure to 10 Gy of X-rays showed a protection factor of 55.1 %, eliminating 39 % of radiation-induced cell death in normal epithelial cells of prostate (PNT2) (p < 0.001). However, in the melanoma cell lines (B16F10) assayed, COL acted not as a radioprotector, but as a sensitizing agent increasing the cellular death by 34 % (p < 0.01) and producing an enhancement ratio of 2.12. CONCLUSIONS:Carnosol may be developed as a radioprotective agent in the non-tumoral cells. However, in the B10F16 melanoma cells, melanogenesis is activated by COL leading to redistribution of the enzymatic balances of glutathione and cysteine-lyase production, which could compromise the intracellular redox defence system. This effect appears as an increase in the capacity of ionizing radiation-induced damage, and thus exhibits a paradoxical protective effect of COL on melanoma cells. жүктеу/скачать 2.03 Mb. Достарыңызбен бөлісу:
|