Last update 01 Nov 2024

ROS1 x BAX x Bcl-2

Last update 01 Nov 2024

Basic Info

Related Targets

ROS1BAXBcl-2

Drugs associated with ROS1 x BAX x Bcl-2

Bcl-2 modulators/BAX modulators/ROS1 inhibitors(Jiangsu University of Science & Technology)

Target

BAX x Bcl-2 x ROS1

Mechanism

BAX modulators [+2]

Active Org.

Jiangsu University of Science & Technology

Originator Org.

Jiangsu University of Science & Technology

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with ROS1 x BAX x Bcl-2

100 Translational Medicine associated with ROS1 x BAX x Bcl-2

0 Patents (Medical) associated with ROS1 x BAX x Bcl-2

419

Literatures (Medical) associated with ROS1 x BAX x Bcl-2

01 Nov 2024·Toxicology

Alendronate sodium induces G1 phase arrest and apoptosis in human umbilical vein endothelial cells by inhibiting ROS-mediated ERK1/2 signaling

Article

Author: Shao, Yi-Ting ; Chen, Zheng ; Tu, Shao-Qin ; Hou, Yu-Luan ; Mai, Zhi-Hui ; Wang, Yu-Xuan ; Chen, Lin ; Ai, Hong ; Wei, Jia-Ming ; Zhang, Sai ; Feng, Yi

Bisphosphonates are potent bone resorption inhibitors, among which alendronate sodium (ALN) is commonly prescribed for most osteoporosis patients, but long-term application of ALN can cause bisphosphonate-related osteonecrosis of jaw (BRONJ), the pathogenesis of which remains unclear. Previous studies have suggested that bisphosphonates cause jaw ischemia by affecting the biological behavior of vascular endothelial cells, leading to BRONJ. However, the impacts of ALN on vascular endothelial cells and its mechanism remain unclear. The purpose of this work is to assess the influence of ALN on human umbilical vein endothelial cells (HUVECs) and clarify the molecular pathways involved. We found that high concentration of ALN induced G1 phase arrest in HUVECs, demonstrated by downregulation of Cyclin D1 and Cyclin D3. Moreover, high concentration of ALN treatment showed pro-apoptotic effect on HUVECs, demonstrated by increased levels of the cleaved caspase-3, the cleaved PARP and Bax, along with decreased levels of anti-apoptotic protein Bcl-2. Further experiments showed that ERK1/2 phosphorylation was decreased. Additionally, ALN provoked the build-up of reactive oxygen species (ROS) in HUVECs, leading to ERK1/2 pathway suppression. N-acetyl-L-cysteine (NAC), a ROS scavenger, efficiently promoted the ERK1/2 phosphorylation and mitigated the G1 phase arrest and apoptosis triggered by ALN in HUVECs. PD0325901, an inhibitor of ERK1/2 that diminishes the ERK1/2 phosphorylation enhanced the ALN-induced G1 phase arrest and apoptosis in HUVECs. These findings show that ALN induces G1 phase arrest and apoptosis through ROS-mediated ERK1/2 pathway inhibition in HUVECs, providing novel insights into the pathogenic process, prevention and treatment of BRONJ in individuals receiving extended use of ALN.

01 Nov 2024·Translational Oncology

Oxazine drug-seed induces paraptosis and apoptosis through reactive oxygen species/JNK pathway in human breast cancer cells

Article

Author: Ahn, Kwang Seok ; Lobie, Peter E ; Alharbi, Sulaiman Ali ; Yang, Jirui ; Pandey, Vijay ; Chinnathambi, Arunachalam ; Venkantesha, Keerthikumara ; Kim, Na Young ; Swamynayaka, Ananda ; Nagaraja, Omantheswara ; Basappa, Basappa ; Sukhorukov, Alexey ; Dukanya, Dukanya ; Madegowda, Mahendra ; Girimanchanaika, Swamy S ; Sethi, Gautam ; Vishwanath, Divakar ; Basappa, Shreeja

Small molecule-driven JNK activation has been found to induce apoptosis and paraptosis in cancer cells. Herein pharmacological effects of synthetic oxazine (4aS, 7aS)-3-((4-(4‑chloro-2-fluorophenyl)piperazin-1-yl)methyl)-4-phenyl-4, 4a, 5, 6, 7, 7a-hexahydrocyclopenta[e] [1,2]oxazine (FPPO; BSO-07) on JNK-driven apoptosis and paraptosis has been demonstrated in human breast cancer (BC) MDA-MB231 and MCF-7 cells respectively. BSO-07 imparted significant cytotoxicity in BC cells, induced activation of JNK, and increased intracellular reactive oxygen species (ROS) levels. It also enhanced the expression of apoptosis-associated proteins like PARP, Bax, and phosphorylated p53, while decreasing the levels of Bcl-2, Bcl-xL, and Survivin. Furthermore, the drug altered the expression of proteins linked to paraptosis, such as ATF4 and CHOP. Treatment with N-acetyl-cysteine (antioxidant) or SP600125 (JNK inhibitor) partly reversed the effects of BSO-07 on apoptosis and paraptosis. Advanced in silico bioinformatics, cheminformatics, density Fourier transform and molecular electrostatic potential analysis further demonstrated that BSO-07 induced apoptosis and paraptosis via the ROS/JNK pathway in human BC cells.

01 Nov 2024·Science of The Total Environment

High fluoride aggravates cadmium-mediated nephrotoxicity of renal tubular epithelial cells through ROS-PINK1/Parkin pathway

Article

Author: Liu, Jiaqi ; Zhao, Zhenqin ; Li, Dashuan ; Sun, Lu ; Zhang, Cheng ; Zhang, Qinghai ; Yang, Chaolian ; Sun, Dali

Fluoride (F) and cadmium (Cd) as well known environmental pollutants can cause nephrotoxicity to damage human health, while the joint toxicity of F and Cd to the renal tubular epithelial cells remains still elusive. The interactive influence between F and Cd in oxidative stress, apoptosis, and mitochondrial autophagy of renal tubular epithelial cells was explored. Cells were submitted to varying concentrations with of NaF (1, 5, 10, and 15 μg/mL) combined with CdCl₂·2.5H₂O (1 μg/mL) for 12 h. Following this, the combined cytotoxicity was assessed. Our results show that different doses of F had varying effects on Cd-mediated nephrotoxicity, with a synergistic effect observed in the high F (15 μg/mL) co-treated with Cd. In response to the Cd induction, the high F treatment resulted in the formation of multiple autophagosomes and notably increased the levels of LDH, ROS, and MMP. It also elevated the MDA contents while decreasing the activities of SOD, GSH-Px, and CAT. Additionally, it yielded a higher Bax/Bcl-2 ratio, which further promotes the apoptotic process. The treatment also disturbed energy metabolism, resulting in a reduction of both ATP and ADP. Furthermore, autophagy-related genes and proteins, including PINK1, Parkin, LC3A, LC3B, and SQSTM1, were significantly improved. In brief, high F of 15 μg/mL aggravated Cd-mediated nephrotoxicity of renal tubular epithelial cells via the ROS-PINK1/Parkin pathway.

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