Search

Many cancer cells critically rely on antioxidant systems for cell survival and are vulnerable to further oxidative impairment triggered by agents generating reactive oxygen species (ROS). Therefore, the classical design and development of inhibitors that target antioxidant defense enzymes such as thioredoxin reductase (TrxR) can be a promising anticancer strategy. Herein, it is shown that a gold(I) complex containing an oleanolic acid derivative (4 b) induces apoptosis of ovarian cancer A2780 cells by activating endoplasmic reticulum stress (ERS). It can inhibit TrxR enzyme activity to elevate ROS, mediate ERS and mitochondrial dysfunction, and finally leads to cell cycle arrest and apoptosis of A2780 cells. Notably, this complex inhibits A2780 xenograft tumor growth accompanied by increased ERS level and decreased TrxR activity in tumor tissues., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: As a key enzyme of m6A methylation modification, methyltransferase-like 14 (METTL14) is involved in many physiological and pathophysiological processes. This study aims to explore the effect of METTL14 on the viability of osteosarcoma cells and explain the underlying molecular mechanism. Methods: We detected the content of METTL14 in osteosarcoma tissue by qRT-PCR and Western blot. Experiments such as transwell, EdU, and CCK-8 have demonstrated the effect of METTL14 on osteosarcoma cell activity. In addition, the regulation of caspase-3 by METL14 was determined by Western blot. We used caspase-3 inhibitor to further reverse the effect of METTL14 on osteosarcoma cell apoptosis. Results: We found that the expression of METTL14 in osteosarcoma cells was reduced compared with normal tissues. METTL14 overexpression significantly reduced the proliferation, migration, invasion and apoptosis of osteosarcoma cells. Inhibition of METL14 showed the opposite result. We have demonstrated that METTL14 finally achieves apoptosis by activating caspase-3. Conclusion: We have demonstrated that METTL14 has effects on osteosarcoma cell proliferation, migration, and invasion and promotes cell apoptosis by activating caspase-3, which may become a potential therapeutic target for osteosarcoma. [ABSTRACT FROM AUTHOR]

Many cancer cells critically rely on antioxidant systems for cell survival and are vulnerable to further oxidative impairment triggered by agents generating reactive oxygen species (ROS). Therefore, the classical design and development of inhibitors that target antioxidant defense enzymes such as thioredoxin reductase (TrxR) can be a promising anticancer strategy. Herein, it is shown that a gold(I) complex containing an oleanolic acid derivative (4 b) induces apoptosis of ovarian cancer A2780 cells by activating endoplasmic reticulum stress (ERS). It can inhibit TrxR enzyme activity to elevate ROS, mediate ERS and mitochondrial dysfunction, and finally leads to cell cycle arrest and apoptosis of A2780 cells. Notably, this complex inhibits A2780 xenograft tumor growth accompanied by increased ERS level and decreased TrxR activity in tumor tissues. [ABSTRACT FROM AUTHOR]

Tafazzin has been found to be associated with tumor progression. Mitochondrial homeostasis regulates cancer cell viability and metastasis. However, the roles of Tafazzin and mitochondrial homeostasis in thyroid cancer have not been explored. The aim of our study is to investigate the influences of Tafazzin on thyroid cancer apoptosis with a focus on mitochondrial fission. Our results indicated that Tafazzin deletion induced death in thyroid cancer via apoptosis. Biological analysis demonstrated that mitochondrial stress, including mitochondrial bioenergetics disorder, mitochondrial oxidative stress, and mitochondrial apoptosis, was activated by Tafazzin deletion. Furthermore, we found that Tafazzin affected mitochondrial stress by triggering inverted formin 2 (INF2)‐related mitochondrial fission. The loss of INF2 sustained mitochondrial function and promoted cancer cell survival. Molecular investigation illustrated that Tafazzin regulated INF2 expression via the JNK signaling pathway; moreover, the blockade of JNK prevented Tafazzin‐mediated INF2 expression and improved cancer cell survival. Taken together, our results highlight the key role of Tafazzin as a master regulator of thyroid cancer viability via the modulation of INF2‐related mitochondrial fission and the JNK signaling pathway. These findings defined Tafazzin deletion and INF2‐related mitochondrial fission as tumor suppressors that act by promoting cancer apoptosis via the JNK signaling pathway, with potential implications for new approaches to thyroid cancer therapy. [ABSTRACT FROM AUTHOR]