scholarly journals Resveratrol Derivative, Trans-3, 5, 4 ′ -Trimethoxystilbene Sensitizes Osteosarcoma Cells to Apoptosis via ROS-Induced Caspases Activation

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Yu Feng ◽  
Jacob Clayton ◽  
Wildman Yake ◽  
Jinke Li ◽  
Weijia Wang ◽  
...  

Numerous studies have shown that resveratrol can induce apoptosis in cancer cells. Trans-3, 5, 4 ′ -trimethoxystilbene (TMS), a novel derivative of resveratrol, is a more potent anticancer compound than resveratrol and can induce apoptosis in cancer cells. Herein, we examined the mechanisms involved in TMS-mediated sensitization of human osteosarcoma (143B) cells to TNF-related apoptosis-inducing ligand- (TRAIL-) induced apoptosis. Our results showed that cotreatment with TSM and TRAIL activated caspases and increased PARP-1 cleavage in 143B cells. Decreasing cellular ROS levels using NAC reversed TSM- and TRAIL-induced apoptosis in 143B cells. NAC abolished the upregulated expression of PUMA and p53 induced by treatment with TRAIL and TSM. Silencing the expression of p53 or PUMA using RNA interference attenuated TSM-mediated sensitization of 143B cells to TRAIL-induced apoptosis. Knockdown of Bax also reversed TSM-induced sensitization of 143B cell to TRAIL-mediated apoptotic cell death. These results indicate that cotreatment with TRAIL and TSM evaluated intracellular ROS level, promoted DNA damage, and activated the Bax/PUMA/p53 pathway, leading to activation of both mitochondrial and caspase-mediated apoptosis in 143B cells. Orthotopic implantation of 143B cells in mice also demonstrated that cotreatment with TRAIL and TSM reversed resistance to apoptosis in cells without obvious adverse effects in normal cells.


BMC Cancer ◽  
2011 ◽  
Vol 11 (1) ◽  
Author(s):  
David J Taylor ◽  
Christine E Parsons ◽  
Haiyong Han ◽  
Arul Jayaraman ◽  
Kaushal Rege


1998 ◽  
Vol 34 (6) ◽  
pp. 434-435 ◽  
Author(s):  
Chari A. Bachman ◽  
Daniel A. Bills ◽  
Shyamal K. Majumdar


1998 ◽  
Vol 274 (6) ◽  
pp. G1061-G1067 ◽  
Author(s):  
Hitoshi Sawaoka ◽  
Sunao Kawano ◽  
Shingo Tsuji ◽  
Masahiko Tsujii ◽  
Edhi S. Gunawan ◽  
...  

To clarify the role of mitogen-inducible cyclooxygenase (COX-2) in the development of malignant tumors, we investigated the effects of COX-2 inhibitors on the growth of gastric cancer xenografts in nude mice in vivo. MKN45 gastric cancer cells (5 × 106cells/animal) that overexpress COX-2 were inoculated subcutaneously into athymic mice. NS-398, a specific COX-2 inhibitor, or indomethacin, a nonspecific COX-2 inhibitor, was administered orally to animals every day for 20 days. These drugs reduced the tumor volume significantly. Immunohistochemistry using bromodeoxyuridine, nick end labeling, and electron microscopy showed that NS-398 induced apoptosis in cancer cells in a dose-dependent manner and inhibited cancer cell replication slightly. Indomethacin also induced apoptosis and suppressed replication of tumor cells. There was a significant negative correlation between tumor volume and apoptotic cell number within the tumor. These results are consistent with the hypothesis that COX-2 inhibitors suppress growth of gastric cancer xenografts mainly by inducing apoptosis and suppressing replication of the neoplastic cells. It follows that COX-2 plays an important role in the development of gastric cancer.





2012 ◽  
Vol 13 (12) ◽  
pp. 15343-15359 ◽  
Author(s):  
Ewelina Szliszka ◽  
Dagmara Jaworska ◽  
Małgorzata Ksek ◽  
Zenon Czuba ◽  
Wojciech Król


Molecules ◽  
2020 ◽  
Vol 25 (1) ◽  
pp. 207 ◽  
Author(s):  
Yi-Yue Wang ◽  
Jun Hyeok Kwak ◽  
Kyung-Tae Lee ◽  
Tsegaye Deyou ◽  
Young Pyo Jang ◽  
...  

The seeds of Millettia ferruginea are used in fishing, pesticides, and folk medicine in Ethiopia. Here, the anti-cancer effects of isoflavones isolated from M. ferruginea were evaluated in human ovarian cancer cells. We found that isoflavone ferrugone and 6,7-dimethoxy-3’,4’-methylenedioxy-8-(3,3-dimethylallyl)isoflavone (DMI) had potent cytotoxic effects on human ovarian cancer cell A2780 and SKOV3. Ferrugone and DMI treatment increased the sub-G1 cell population in a dose-dependent manner in A2780 cells. The cytotoxic activity of ferrugone and DMI was associated with the induction of apoptosis, as shown by an increase in annexin V-positive cells. Z-VAD-fmk, a broad-spectrum caspase inhibitor, and z-DEVD-fmk, a caspase-3 inhibitor, significantly reversed both the ferrugone and DMI-induced apoptosis, suggesting that cell death stimulated by the isoflavones is mediated by caspase-3-dependent apoptosis. Additionally, ferrugone-induced apoptosis was found to be caspase-8-dependent, while DMI-induced apoptosis was caspase-9-dependent. Notably, DMI, but not ferrugone, increased the intracellular levels of reactive oxygen species (ROS), and antioxidant N-acetyl-L-cysteine (NAC) attenuated the pro-apoptotic activity of DMI. These data suggest that DMI induced apoptotic cell death through the intrinsic pathway via ROS production, while ferrugone stimulated the extrinsic pathway in human ovarian cancer cells.



2007 ◽  
Vol 1095 (1) ◽  
pp. 521-526 ◽  
Author(s):  
E. LEE ◽  
R. ENOMOTO ◽  
C. SUZUKI ◽  
M. OHNO ◽  
T. OHASHI ◽  
...  


Metallomics ◽  
2014 ◽  
Vol 6 (8) ◽  
pp. 1480-1490 ◽  
Author(s):  
Zuandi Luo ◽  
Lianling Yu ◽  
Fang Yang ◽  
Zhennan Zhao ◽  
Bo Yu ◽  
...  

Ruthenium polypyridyl complexes inhibit cancer growth by targeting TrxR and promote the intracellular ROS generation, ultimately triggering mitochondria-mediated cell apoptosis.



2016 ◽  
Vol 7 (8) ◽  
pp. 4922-4929 ◽  
Author(s):  
V. H. S. van Rixel ◽  
B. Siewert ◽  
S. L. Hopkins ◽  
S. H. C. Askes ◽  
A. Busemann ◽  
...  

In this work, two new photopharmacological ruthenium prodrugs are described that can be activated by green light. Cell death occurs via apoptosis; it is not a consequence of singlet oxygen generation, but of light-induced photosubstitution reactions.



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