| Source: HalifaxProj (inhibit) |
| Type: |
| The proteasome is a crucial component of the cellular machinery responsible for degrading ubiquitinated proteins, which are proteins tagged for destruction. This process is essential for maintaining cellular homeostasis, regulating the cell cycle, and controlling various signaling pathways. Many cancer cells exhibit increased expression of proteasome subunits. This upregulation can enhance the proteasome's capacity to degrade proteins, including those that regulate cell cycle progression and apoptosis, thereby promoting tumor growth and survival. Proteasome inhibitors act by blocking the activity of the proteasome, a crucial cellular complex responsible for degrading most intracellular proteins. -The proteasome is responsible for degrading ubiquitin-tagged proteins, including misfolded, damaged, or regulatory proteins. By inhibiting the proteasome’s function, these proteins accumulate within the cell. -Accumulated proteins can lead to increased cellular stress, particularly in the endoplasmic reticulum (ER) where misfolded proteins build up. This stress can trigger the unfolded protein response (UPR), which, if unresolved, may lead to apoptosis (programmed cell death). -It is well known that ROS plays an important role in proteasome inhibition-induced cell death. Inhibitor Drugs: bortezomib (Velcade) and carfilzomib Natural Product Inhibitors: -Gambogic Acid: -Lactacystin: Origin: Isolated from the bacterium Streptomyces lactacystinaeus. -Epoxomicin is a highly selective and potent inhibitor of the proteasome. Its structure has informed the design of synthetic drugs such as carfilzomib. -Syringolin A -Tyropeptins -EGCG -Withania somnifera (commonly known as Ashwagandha). -Celastrol Origin: Derived from plants of the Tripterygium genus (commonly known as Thunder God Vine). |
| Prostate Cancer: Alterations in genes such as ERG, SPOP, MYC, androgen receptor (AR), and CHD1, drive PCa progression. TP53 is the most commonly mutated gene in human cancer. HH↑, GLI-1↑, SHH↑ P53↓ The loss of p53 and/or other tumor suppressor genes, reduced capacity for DNA repair, the dysfunction of telomerase activity, and changes in the pathways that govern the growth of cells also mediate the progression of Pca. It has been well documented that Ca2+ influx and MDR1 upregulation are highly associated with GEM metabolism in human pancreatic carcinoma. Increased Growth factor IGF-1/IGF-1R axis activation mediated by both PI3K/Akt or RAF/MEK/ERK system and AR expression remains important in the development and progression of prostate cancer. It has been demonstrated that prostate cancer cells are relatively sensitive to heat stress. Long non-coding RNA MALAT1 has been reported as an oncogenic target in multiple types of cancers, including PC. |
| 5171- | Ash, | The tumor proteasome is a primary target for the natural anticancer compound Withaferin A isolated from "Indian winter cherry" |
| - | vitro+vivo, | Pca, | LNCaP | - | vitro+vivo, | Pca, | PC3 |
| 2013- | CAP, | Capsaicin, a component of red peppers, inhibits the growth of androgen-independent, p53 mutant prostate cancer cells |
| - | in-vitro, | Pca, | PC3 | - | in-vitro, | Pca, | LNCaP | - | in-vitro, | Pca, | DU145 | - | in-vivo, | NA, | NA |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
Filter Conditions: Pro/AntiFlg:% IllCat:% CanType:22 Cells:% prod#:% Target#:262 State#:% Dir#:1
wNotes=0 sortOrder:rid,rpid