scholarly journals The Mechanisms of Yu Ping Feng San in Tracking the Cisplatin-Resistance by Regulating ATP-Binding Cassette Transporter and Glutathione S-Transferase in Lung Cancer Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Yingqing Du ◽  
Yuzhong Zheng ◽  
Ciel Xiaomei Yu ◽  
Lishan Zhong ◽  
Yafang Li ◽  
...  

Cisplatin is one of the first line anti-cancer drugs prescribed for treatment of solid tumors; however, the chemotherapeutic drug resistance is still a major obstacle of cisplatin in treating cancers. Yu Ping Feng San (YPFS), a well-known ancient Chinese herbal combination formula consisting of Astragali Radix, Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix, is prescribed as a herbal decoction to treat immune disorders in clinic. To understand the fast-onset action of YPFS as an anti-cancer drug to fight against the drug resistance of cisplatin, we provided detailed analyses of intracellular cisplatin accumulation, cell viability, and expressions and activities of ATP-binding cassette transporters and glutathione S-transferases (GSTs) in YPFS-treated lung cancer cell lines. In cultured A549 or its cisplatin-resistance A549/DDP cells, application of YPFS increased accumulation of intracellular cisplatin, resulting in lower cell viability. In parallel, the activities and expressions of ATP-binding cassette transporters and GSTs were down-regulated in the presence of YPFS. The expression of p65 subunit of NF-κB complex was reduced by treating the cultures with YPFS, leading to a high ratio of Bax/Bcl-2, i.e. increasing the rate of cell death. Prim-O-glucosylcimifugin, one of the abundant ingredients in YPFS, modulated the activity of GSTs, and then elevated cisplatin accumulation, resulting in increased cell apoptosis. The present result supports the notion of YPFS in reversing drug resistance of cisplatin in lung cancer cells by elevating of intracellular cisplatin, and the underlying mechanism may be down regulating the activities and expressions of ATP-binding cassette transporters and GSTs.

2011 ◽  
Vol 23 (5) ◽  
pp. 1958-1970 ◽  
Author(s):  
Michael Bessire ◽  
Sandra Borel ◽  
Guillaume Fabre ◽  
Luis Carraça ◽  
Nadia Efremova ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jin Won Park ◽  
Kyung-Ho Jung ◽  
Youngjoo Byun ◽  
Jin Hee Lee ◽  
Seung Hwan Moon ◽  
...  

Author(s):  
Burak Yazgan ◽  
Seda Mesci ◽  
Nagihan Bayık ◽  
Maşuk Akşahin ◽  
Gönül Yenilmez Çiftçi ◽  
...  

Background: As a class with biological properties, such as anti-cancer, anti-bacterial, anti-HIV, and various physical effects, phosphazene derivatives constitute the most striking part of inorganic compounds. Anthraquinones, on the other hand, are a broad family of compounds with a wide variety of biological properties; the biologically active anthraquinones have been used as valuable tool compounds for biochemical and pharmacological research. Objective: In this study, we aimed to investigate the effect of the anthraquinone substituted cyclotriphosphazene compounds on apoptosis and drug resistance in MCF-7 and DLD-1 cells. Methods: In breast and colon cells, mRNA levels of multi-drug resistance genes (ABCB1, ABCC3, ABCC10, ABCC11, and ABCG2), apoptotic genes (BAX, BCL-2, p53, and PARP), heat shock (HSP27, HSP40, HSP60, HSP90α) and endoplasmic reticulum chaperone genes (GRP78, and GRP94) were determined by the qPCR method. The amount of proteins of the cell cycle, HSPs, apoptosis, and related signaling pathways were measured by the membrane array kits. Results: Compounds 2, 3, 4, and 7 showed the most potent results on the ATP-binding cassette genes in both breast and colon cancer cells. These compounds have a remarkable effect on apoptotic, heat shock, and ER chaperone genes in cancer cells. Besides, these compounds induced protein levels of pro-apoptotic pathways, leading to apoptosis by inhibiting anti-apoptotic pathways. Also, these compounds decreased HSPs. Conclusion: These compounds have potential properties that eliminate drug resistance, suppress heat shock and ER chaperone genes, and drag cells to apoptotic cell death and are notable for drug studies.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Agustina Dwi Retno Nurcahyanti ◽  
Lia Kusmita ◽  
Michael Wink

Abstract Objective Cisplatin is a conventional anticancer drug that generates reactive oxygen species and causes apoptosis. However, many cancer cells develop alterations in the ATP binding cassette transporter responsible for the uptake and efflux process, which leads to resistance. Many natural products have shown potential to compete with ATP binding cassette transporter and may sensitize resistant cells to cisplatin. Studies have shown pro-oxidant effect of carotenoids that promote apoptosis of cancer cells. Bixin and fucoxanthin are well-known carotenoids with known antioxidant properties, however their bioactivity in lung cancer cells, clinically known to develop resistance due to ATP binding cassette transporter, has been minimally studied. This study is the first to investigate the potential of bixin and fucoxanthin to sensitize human lung cancer cell line, A549 and cervical cancer cell line, HeLa, to cisplatin. Drug combination method developed by Chou and Talalay theorem was employed. Result Employing the best combination ratio, this study shows selective sensitization of cancer cells to cisplatin after bixin and fucoxanthin treatment. Further study on the mechanism of action in specific types of cancer cells is warranted. It may improve cisplatin sensitivity in tumors and rational use of cancer drugs. Graphical Abstract


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