Synthesis and biological evaluation of novel isoxazole-piperazine hybrids as potential anti-cancer agents with inhibitory effect on liver cancer stem cells

2021 ◽  
Vol 221 ◽  
pp. 113489
Author(s):  
Kübra İbiş ◽  
Esra Nalbat ◽  
Burcu Çalışkan ◽  
Deniz Cansen Kahraman ◽  
Rengul Cetin-Atalay ◽  
...  
2019 ◽  
Vol 509 (1) ◽  
pp. 268-274 ◽  
Author(s):  
Kosuke Inamura ◽  
Yuji Komizu ◽  
Mami Yamakuchi ◽  
Seiichi Ishida ◽  
Yoko Matsumoto ◽  
...  

Author(s):  
Milad Ashrafizadeh ◽  
Shahram Taeb ◽  
Hamed Haghi-Aminjan ◽  
Shima Afrashi ◽  
Kave Moloudi ◽  
...  

: Resistance of cancer cells to therapy is a challenge for achieving an appropriate therapeutic outcome. Cancer (stem) cells possess several mechanisms for increasing their survival following exposure to toxic agents such as chemotherapy drugs, radiation as well as immunotherapy. Evidences show that apoptosis plays a key role in response of cancer (stem) cells and their multi drug resistance. Modulation of both intrinsic and extrinsic pathways of apoptosis can increase efficiency of tumor response and amplify the therapeutic effect of radiotherapy, chemotherapy, targeted therapy and also immunotherapy. To date, several agents as adjuvant have been proposed to overcome resistance of cancer cells to apoptosis. Natural products are interesting because of low toxicity on normal tissues. Resveratrol is a natural herbal agent that has shown interesting anti-cancer properties. It has been shown to kill cancer cells selectively, while protecting normal cells. Resveratrol can augment reduction/oxidation (redox) reactions, thus increases the production of ceramide and the expression of apoptosis receptors such as Fas ligand (FasL). Resveratrol also triggers some pathways which induce mitochondrial pathway of apoptosis. On the other hand, resveratrol has an inhibitory effect on anti-apoptotic mediators such as nuclear factor κ B (NFκB), cyclooxygenase-2 (COX-2), phosphatidylinositol 3–kinase (PI3K) and mTOR. In this review, we explain the modulatory effects of resveratrol on apoptosis, which can augment the therapeutic efficiency of anti-cancer drugs or radiotherapy.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wang Yin ◽  
Dongxi Xiang ◽  
Tao Wang ◽  
Yumei Zhang ◽  
Cuong V. Pham ◽  
...  

AbstractTwo ATP-binding cassette transporters, ABCB1/MDR1 and ABCG2/BCRP, are considered the most critical determinants for chemoresistance in hepatocellular carcinoma. However, their roles in the chemoresistance in liver cancer stem cells remain elusive. Here we explored the role of inhibition of MDR1 or ABCG2 in sensitizing liver cancer stem cells to doxorubicin, the most frequently used chemotherapeutic agent in treating liver cancer. We show that the inhibition of MDR1 or ABCG2 in Huh7 and PLC/PRF/5 cells using either pharmacological inhibitors or RNAi resulted in the elevated level of intracellular concentration of doxorubicin and the accompanied increased apoptosis as determined by confocal microscopy, high-performance liquid chromatography, flow cytometry, and annexin V assay. Notably, the inhibition of MDR1 or ABCG2 led to the reversal of the chemoresistance, as evident from the enhanced death of the chemoresistant liver cancer stem cells in tumorsphere-forming assays. Thus, the elevation of effective intracellular concentration of doxorubicin via the inhibition of MDR1 or ABCG2 represents a promising future strategy that transforms doxorubicin from a traditional chemotherapy agent into a robust killer of liver cancer stem cells for patients undergoing transarterial chemoembolization.


Tumor Biology ◽  
2015 ◽  
Vol 37 (6) ◽  
pp. 8047-8055 ◽  
Author(s):  
Beibei Zhai ◽  
Xiaofeng Zhang ◽  
Bin Sun ◽  
Lu Cao ◽  
Linlin Zhao ◽  
...  

Author(s):  
Izabela Zarębska ◽  
Arkadiusz Gzil ◽  
Justyna Durślewicz ◽  
Damian Jaworski ◽  
Paulina Antosik ◽  
...  

2015 ◽  
Vol 10 (2) ◽  
pp. 455 ◽  
Author(s):  
Jian-Bo Zhou ◽  
Gang Peng ◽  
Yu-Cheng Jia ◽  
Jun Li ◽  
Jia Wang ◽  
...  

<p>The present study demonstrates the effects of triptolide, one of the constituents from Tripterygium wilfordii, on the self‑renewal capacity of human hepatocellular carcinoma. The investigation revealed that triptolide markedly prevented the proliferation of liver cancer stem cells (LCSCs). For the LCSCs the minimum inhibitory concentration of triptolide was 0.6 μM. There was a significant and obvious decrease in the capacity of LCSCs to form self-sphere. Furthermore, triptolide reduced the sphere-forming capacity of LCSCs along with inhibition of β‑catenin expression. However, the exposure of triptolide-treated cells to lithium chloride, an activator the Wnt/β-catenin signaling pathway, reversed the triptolide-induced inhibition of β-catenin expression and inhibited the self-renewal capacity. Therefore, triptolide effectively eradicates LCSCs through the inhibition of β-catenin protein and may act as a novel agent for the treatment of hepatocellular carcinoma.</p><p> </p>


Gene ◽  
2019 ◽  
Vol 687 ◽  
pp. 73-81 ◽  
Author(s):  
Cheng Yang ◽  
Wen-chang Cai ◽  
Zhi-tao Dong ◽  
Jun-wu Guo ◽  
Yi-jun Zhao ◽  
...  

2014 ◽  
Vol 47 (6) ◽  
pp. 478-482 ◽  
Author(s):  
H. Zhang ◽  
W.J. Chang ◽  
X.Y. Li ◽  
N. Zhang ◽  
J.J. Kong ◽  
...  

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