scholarly journals ALTERING THE EXPRESSION OF P-GLYCOPROTEIN RESPONSIBLE FOR CHEMOTHERAPEUTIC DRUG RESISTANCE IN HEPG2 CELL LINE POST-TREATMENT WITH UREA AND β-MERCAPTOETHANOL

Author(s):  
PROMA CHAKRABORTY ◽  
MANI RAMAKRISHNAN ◽  
KUMAR KM

Objective: The objective of this study is to alter the expression of p-glycoprotein (p-gp) pump proteins in HepG2 cells after treating with urea and β-mercaptoethanol (BME) (lead compounds). The most common cause for resistance to a broad range of anticancer drugs is influenced by overexpression of p-gp pumps that detect and eject anticancer drugs from the cancer cell. Altering the expression of these proteins will reduce the efflux action and enhance the drug retention eventually killing the cancer cell. Materials and Methods: 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyl tetrazolium bromide (MTT) assay was carried out to measure the cell viability (HepG2 cells) post-treatment with the lead compounds followed by flow cytometric analysis for protein expression studies. Results: MTT assay confirms that the viability of HepG2 cells reduces as the concentrations of the lead compounds are increased. Flow cytometric analysis confirms reduced p-gp expression in HepG2 cells post-treatment with urea and BME. Compare to BME, urea turns out to be a potential compound in altering the expression of p-gp. Conclusion: The present cell line study confirms that urea and BME are potential compounds which are able to reduce the p-gp expression inHepG2 cells.

2002 ◽  
Vol 28 (3) ◽  
pp. 141-148 ◽  
Author(s):  
Gui Se Ra Lee ◽  
Ki Sung Ryu ◽  
Jong Gu Rha ◽  
Soo Pyung Kim ◽  
Sung Eun Namkoong ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Jing-Quan Wang ◽  
Zhuo-Xun Wu ◽  
Yuqi Yang ◽  
Jin-Sui Li ◽  
Dong-Hua Yang ◽  
...  

Ovarian cancer is one of the leading female malignancies which accounts for the highest mortality rate among gynecologic cancers. Surgical cytoreduction followed by chemotherapy is the mainstay of treatment. However, patients with recurrent ovarian cancer are likely to exhibit resistance to chemotherapy due to reduced sensitivity to chemotherapeutic drugs. Adenosine triphosphate (ATP)-binding cassette (ABC) transporters have been extensively studied as multidrug resistance (MDR) mediators since they are responsible for the efflux of various anticancer drugs. Multidrug resistance protein 7 (MRP7, or ABCC10) was discovered in 2001 and revealed to transport chemotherapeutic drugs. Till now, only limited knowledge was obtained regarding its roles in ovarian cancer. In this study, we established an MRP7-overexpressing ovarian cancer cell line SKOV3/MRP7 via transfecting recombinant MRP7 plasmids. The SKOV3/MRP7 cell line was resistant to multiple anticancer drugs including paclitaxel, docetaxel, vincristine and vinorelbine with a maximum of 8-fold resistance. Biological function of MRP7 protein was further determined by efflux-accumulation assays. Additionally, MTT results showed that the drug resistance of the SKOV3/MRP7 cells was reversed by cepharanthine, a known inhibitor of MRP7. Moreover, we also found that the overexpression of MRP7 enhanced the migration and epithelial-mesenchymal transition (EMT) induction. In conclusion, we established an in vitro model of MDR in ovarian cancer and suggested MRP7 overexpression as the leading mechanism of chemoresistance in this cell line. Our results demonstrated the potential relationship between MRP7 and ovarian cancer MDR.


2009 ◽  
Vol 66 (4) ◽  
pp. 765-771 ◽  
Author(s):  
Stefan Harmsen ◽  
I. Meijerman ◽  
C. L. Febus ◽  
R. F. Maas-Bakker ◽  
J. H. Beijnen ◽  
...  

2005 ◽  
Vol 17 (9) ◽  
pp. 122 ◽  
Author(s):  
D. Aridi ◽  
D. Pellicci ◽  
P. Hutchinson ◽  
M. P. Hedger

Testicular leukocytes are assumed to be involved in immunological surveillance against infection and tumours as well as regulation of local immune responses. They are implicated in mechanisms that make the testis a successful site for tissue transplantation in both rats and mice. Our previous studies using multi-colour fluorescence flow cytometric analysis to examine isolated testicular leukocytes in the rat testis have established the existence of a significant population of predominantly CD8+ T cells and a comparable number of lymphocytes expressing natural killer (NK) cell markers (NK and NKT cells). The functional activity of these testicular NK and NKT cells subsequently has been confirmed by a standard flow cytometric cytotoxicity assay using an NK-sensitive tumour cell line (YAC-1) and an NKT-sensitive tumour cell line (U937). Similar analyses of mouse testicular leukocytes have shown a slightly different pattern. The data indicate that mouse testicular lymphocytes comprise T cells, NK cells, and NKT cells, similar to the rat testis. However, while the apparent numerical densities of T cells in rat and mouse testes were similar, the numbers of NK and NKT cells were considerably lower in the mouse. Mouse testicular NKT cells were positive for staining with the tetramer CD1d/αGC, which is used to identify classical NKT cells, whereas rat NKT cells did not stain for this marker. Moreover, the CD8/CD4 T cell ratio in the mouse testis displayed a skewing towards the CD4+ subset. These data highlight the possibility that the immunological environment, and hence the course of immunological events, might be quite different in the testes of the two species. The reasons for these differences are not clear, however they should be taken into account when considering studies of testicular immune processes. Finally, comparative studies of immunological process in the testes of rats and mice may be very informative.


1995 ◽  
Vol 86 (11) ◽  
pp. 1112-1118 ◽  
Author(s):  
Seiji Naito ◽  
Shuji Hasegawa ◽  
Akira Yokomizo ◽  
Hirofumi Koga ◽  
Shuji Kotoh ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Farazul Haque ◽  
Mohd Sajjad Ahmad Khan ◽  
Naif AlQurashi

Cancer is one of the major leading causes of death worldwide. Designing the new anticancer drugs is remained a challenging task due to ensure complexicity of cancer etiology and continuosly emerging drug resistance. Glycolipid biosurfactants are known to possess various biological activities including antimicrobial, anticancer and antiviral properties. In the present study, we sought to decipher the mechanism of action of the glycolipids (lactonic-sophorolipd, acidic-sophorolipid, glucolipid, and bolalipid) against cancer cells using lung cancer cell line (A549), breast cancer cell line (MDA-MB 231), and mouse skin melanoma cell line (B16F10). Scratch assay and fluorescence microscopy revealed that glycolipids inhibit tumorous cell migration possibly by inhibiting actin filaments. Fluorescence activated cell sorter (FACS) analysis exhibited that lactonic sophorolipid and glucolipid both induced the reactive oxygen species, altered the mitochondrial membrane potential (ΔΨ) and finally led to the cell death by necrosis. Furthermore, combinatorial effect of lactonic-sophorolipd and glucolipid demonstrated synergistic interaction on A549 cell line whereas additive effect on MDA-MB 231 and B16F10 cell lines. Our study has highlighted that lactonic-sophorolipd and glucolipid could be useful for developing new anticancer drugs either alone or in combination.


Sign in / Sign up

Export Citation Format

Share Document