As attempt to explain the cytotoxic activity achieved by the tested compounds in the in vitro study, molecular simulation was done to reveal the activity of the tested compounds against four different proteins (CDK2, CYP19, JAK2, and BCL2) which are highly implicated in cancer regulation and progression.
Notably, the results also indicated that GA enhanced the anticancer effects of cisplatin in the inhibition of cancer cell proliferation and the induction of cell apoptosis following elevated Bax expression and suppressed Bcl‑2 expression.
The cellular effects of internalized miRNA-15a on the oncogene protein BCL-2 were investigated at two different concentrations (N/P = 10 and 5), and a reduction of the BCL-2 level was detected at a low concentration (i.e., N/P = 10). miRNA-15a is considered an ideal cancer therapy molecule due to its activity on multiple transcription factors, and the elucidation of the correlation between the concentration of delivered miRNA-15a and the down-/up-regulation of the BCL-2 level, documented for the first time in this work, could be an important contribution to guide its clinical application.
Members of the B-cell lymphoma 2 (BCL2) family of proteins are central regulators of apoptosis, and resistance to apoptosis is one of the hallmarks of cancer.
A carbazole-piperazine hybrid molecule ECPU-0001 was designed and synthesized as a potent BCL-2 targeting agent with effective anticancer cancer activity.
Furthermore, TMPRSS4 promoted cancer cell survival and drug resistance, and both compounds enhanced anoikis sensitivity as well as reduced bcl-2 and survivin levels.
Structure-based pharmacophore modeling aided in the identification of PUMA inhibitors, structure based approach with high throughput screening for the development of Bcl-2 inhibitors, to derive the most relevant protein-protein interactions, anti mitotic agents; I-Kappa-B Kinase β (IKK- β) inhibitor, screening of new class of aromatase inhibitors that can be important targets in cancer therapy.
Connexin 43 (Cx43) protein and its cell-communication channels have been assigned tumor suppressor functions while the anti-apoptotic Bcl-2 (B-cell lymphoma-2) protein has been associated with negative prognostic significance in cancer.
The high values of the obtained classification rates demonstrate that the information provided in this work would be useful to design new drugs with selective inhibitory activities toward Bcl-2 or Bcl-x<sub>L</sub> proteins for more effective treatment of cancer.
As a crucial oncogene, B cell lymphoma-2 (BCL-2) could promote cancer cell survival by inhibiting apoptosis via suppressing activation of proapoptotic proteins, such as BAX and BAK.
Expression correlation analyses between STAB1 and cancer drug targets suggested that patients in the STAB1<sup>low</sup> group are more sensitive to the BCL2 inhibitor venetoclax, and we confirmed it in cell lines.
In this study, the effect of doxorubicin, flavonoid extract of white Morus alba leaf (MFE) and a combination of doxorubicin and flavonoid extract on Bax and Bcl2 levels and caspase 3 activity of cancer A-172 GBM cell line was investigated.
Due to the importance of the BCL-2-regulated apoptosis pathway in cancer development and drug resistance, it is of interest to establish which proteins are most important for melanoma cell survival, though the outcomes of previous studies have been conflicting.
Here we revisit this area and examine the progress and current status of small molecule Bcl-2 inhibitor development, demonstrating the Bcl-2 family as a valid target for cancer therapy and providing successful examples for the discovery of inhibitors that target protein-protein interactions.
It also significantly enhances the apoptotic associated and inhibits the cancer cell proliferative markers expression (p53, Bax, Bcl-2, cleaved caspase 3, cyclin-D1).