Расторопши: семена ранней потенциальных

Discussion

PTEN mutation in some cancer cells was found with distant metastases or tumor invasions, suggesting that PTEN mutation is a late-stage event that may contribute to an invasive and metastatic tumor phenotype.³⁵ A prominent phosphorylation of Bad was observed also, thus suggesting that pro-apoptotic Bad protein was inactivated. It is conceivable that phosphorylated Bad may play a role in the survival of cancer cells and that dephosphorylation by Akt inhibitor may induce cancer cells to undergo apoptosis. Bad phosphorylation may be closely related to aberrant survival, namely, carcinogenesis. In various types of human malignant tumors, an elevated Akt activation has been demonstrated and the mechanisms for Akt activation have been shown to depend on the types of tumors. For example, ovarian carcinomas and endometrial carcinoma have shown to increase Akt activation due to a high frequency of PTEN inactivation.^18,36 In 2005, an article offered new insights into the regulation of the PTEN/AKT pathway and the mechanisms of resistance to tumor genesis. This article also suggested that inhibitors of the AKT pathway should be tested and potentially be developed as new therapeutic agents.³⁷ In the present study, we found that silymarin can inhibit AKT pathway by increasing PTEN. Finally, if the anti-apoptotic protein Bad is inactivated it may directly trigger caspase-dependant cell death.

Silymarin at concentrations of 24–48μg/mL induced apoptotic death by inhibiting Akt activity³⁸ or the p53-dependent pathway,³⁹ decreasing cell viability by 40–20%.³⁸ In contrast to silymarin, silibinin caused cell cycle arrest in the G1 phase in human colon carcinoma HT-29 cells and inhibited cell proliferation rate at concentrations of 75–100μg/mL (about 150–200μM)³³ that is higher than the effective dose of silymarin (<48μg/mL). Also, suppression of growth in human colorectal carcinoma (SW480) by silibinin has been observed at concentrations of 200μM.⁴⁰ It is clear that silymarin has higher potency than silibinin to induce apoptotic cell death. Silibinin is a compound purified from silymarin. However, direct increase of PTEN gene by silymarin is still not observed in silibinin-treated cells. Our study shows that increased expression of PTEN by silibinin is diminished within 4h, but the effect of silymarin continued until the end of experiment. The result of cytotoxicity assays also reflects that silymarin has higher potency than silibinin to induce apoptotic cell death. This point was not mentioned before. However, the pharmacokinetic factors may be important and more in vivo studies are warranted to understand the stability and bioavailability of silymarin for the clinical applications.

Silybin A, silybin B, isosilybin A, isosilybin B, silydianin, silychristin, and isosilychristin were other components isolated from silymarin and they were used to screen the effect on prostate cancer cells.⁷ Then, isosilybin B (one of the active components) was found to cause cell cycle arrest.⁴¹ This may explain why silymarin is more effective for inducing cancer cell apoptosis.

In conclusion, the present study shows, for the first time, that silymarin has a higher potency than silibinin to induce apoptotic cell death in oral cancer. Also, silymarin inhibits the Akt signaling pathway by increasing PTEN expression in FaDu cells and directly affects Bcl-2 family members without other factors. These results provide a rationale for the development of silymarin as a therapeutic agent for oral cancer.


Химические и анти-рак эффективности силибинин против роста и прогрессирования легочного рака.

Использование системного химиотерапевтических препаратов и молекулярно-направленной терапии в лечении больных с местно-распространенным или метастатическим раком легких, рак имеет свои ограничения из-за связанного острая и кумулятивная доза ограничения токсичности и приобретения лекарственной устойчивости. Профилактические и лечебные вмешательства диетическое агентов, в том числе нутрицевтики, которые не являются токсичными, экономически эффективных и физиологически-биологически, формирующиеся подходы в легких рак управления. В связи с этим, силибинин, естественный flavonolignan, были тщательно опробованы, для профилактики и контроля роста легких рак через широкий in vitro и in vivo. Успешные исследования до сих пор, было установлено, что силибинин является эффективным как в одиночку, так и в комбинации с другими агентами (например, химиотерапевтические и эпигенетические агентов) существенно тормозит рост легких раковых клеток. In vivo, его последствия были показаны, чтобы быть опосредовано через ингибирование пролиферации, ангиогенеза и эпигенетических событий, связанных с. Таким образом, настоящий обзор фокусируется на охватывающей эффективность и механизмы силибинин против легких рак.