The antiproliferative activity of ferrocene derivatives against drug-resistant cancer cell lines: A mini review

: Cancer, a highly heterogeneous disease at intra/inter patient levels, remains a serious health problem contributing to significant morbidity and mortality worldwide. Despite great progress in clinical treatment, the concerns impeding the success of conventional cancer chemotherapy is descending efficacy of anticancer agents due to the development of drug resistance especially multiple drug resistance (MDR). Ferrocene derivatives have a different mode of action to the platinum anticancer drugs, and the ferrocene-phenol hybrid ferrocifen exhibits potential activity against drug-resistant cancers. Currently, ferrocifen is in preclinical trial, demonstrating that ferrocene derivatives are useful scaffolds for the development of novel anticancer candidates which are active against drug-resistant cancers. In the present review, the current scenario of ferrocene derivatives including ferrocene metal complexes, hybrids and other derivatives with antiproliferative potential against drug-resistant cancer cell lines is summarized for further rational design.

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Heterogeneity of DNA-damage in ovarian cancer cell lines A2780-WT and multiple drug resistant (mdr) A2780-Dox-5 treated with adriamycin(ADM)

Journal of Cancer Research and Clinical Oncology ◽

10.1007/bf02572181 ◽

1995 ◽

Vol 121 (S1) ◽

pp. A54-A54

Author(s):

C. Schöber ◽

J. Gibbs ◽

M. B. Yin ◽

C. Frank ◽

C. Wroszek ◽

...

Keyword(s):

Ovarian Cancer ◽

Dna Damage ◽

Cell Lines ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Cancer Cell Lines ◽

Multiple Drug ◽

Drug Resistant ◽

Ovarian Cancer Cell Lines ◽

Multiple Drug Resistant

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Role of the MDR-1-Encoded Multiple Drug Resistance Phenotype in Prostate Cancer Cell Lines

The Journal of Urology ◽

10.1016/s0022-5347(17)35838-x ◽

1993 ◽

Vol 150 (5 Part 1) ◽

pp. 1544-1547 ◽

Cited By ~ 55

Author(s):

Gerhard Theyer ◽

Marion Schirmböck ◽

Therese Thalhammer ◽

Edward R. Sherwood ◽

Gerhard Baumgartner ◽

...

Keyword(s):

Prostate Cancer ◽

Drug Resistance ◽

Cell Lines ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Multiple Drug Resistance ◽

Multiple Drug ◽

Prostate Cancer Cell Lines ◽

Mdr 1

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Acquired Drug Resistance Enhances Imidazoquinoline Efflux by P-Glycoprotein

Pharmaceuticals ◽

10.3390/ph14121292 ◽

2021 ◽

Vol 14 (12) ◽

pp. 1292

Author(s):

Anunay J. Pulukuri ◽

Anthony J. Burt ◽

Larissa K. Opp ◽

Colin M. McDowell ◽

Maryam Davaritouchaee ◽

...

Keyword(s):

Drug Resistance ◽

Cell Lines ◽

Cancer Cell ◽

Immune Cells ◽

Rational Design ◽

Cancer Cell Lines ◽

Drug Efflux ◽

Acquired Drug Resistance ◽

P Glycoprotein ◽

Tlr Agonist

Multidrug-Resistant (MDR) cancers attenuate chemotherapeutic efficacy through drug efflux, a process that transports drugs from within a cell to the extracellular space via ABC (ATP-Binding Cassette) transporters, including P-glycoprotein 1 (P-gp or ABCB1/MDR1). Conversely, Toll-Like Receptor (TLR) agonist immunotherapies modulate activity of tumor-infiltrating immune cells in local proximity to cancer cells and could, therefore, benefit from the enhanced drug efflux in MDR cancers. However, the effect of acquired drug resistance on TLR agonist efflux is largely unknown. We begin to address this by investigating P-gp mediated efflux of TLR 7/8 agonists. First, we used functionalized liposomes to determine that imidazoquinoline TLR agonists Imiquimod, Resiquimod, and Gardiquimod are substrates for P-gp. Interestingly, the least potent imidazoquinoline (Imiquimod) was the best P-gp substrate. Next, we compared imidazoquinoline efflux in MDR cancer cell lines with enhanced P-gp expression relative to parent cancer cell lines. Using P-gp competitive substrates and inhibitors, we observed that imidazoquinoline efflux occurs through P-gp and, for Imiquimod, is enhanced as a consequence of acquired drug resistance. This suggests that enhancing efflux susceptibility could be an important consideration in the rational design of next generation immunotherapies that modulate activity of tumor-infiltrating immune cells.

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MDR Gene Expression Analysis of Six Drug-Resistant Ovarian Cancer Cell Lines

BioMed Research International ◽

10.1155/2013/241763 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 55

Author(s):

Radosław Januchowski ◽

Karolina Wojtowicz ◽

Patrycja Sujka-Kordowska ◽

Małgorzata Andrzejewska ◽

Maciej Zabel

Keyword(s):

Ovarian Cancer ◽

Drug Resistance ◽

Cell Lines ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Multiple Drug Resistance ◽

Cancer Cell Lines ◽

Resistant Cell ◽

Cross Resistance ◽

Ovarian Cancer Cell Lines

Ovarian cancer is the leading cause of death among gynaecological malignancies. Multiple drug resistance makes cancer cells insensitive to chemotherapy. In this study, we developed six primary ovarian cancer cell lines (W1MR, W1CR, W1DR, W1VR, W1TR, and W1PR) resistant to drugs such as methotrexate, cisplatin, doxorubicin, vincristine, topotecan, and paclitaxel. A chemosensitivity assay MTT test was performed to assess drug cross-resistance. Quantitative real-time polymerase chain reaction and Western blot were also performed to determine mRNA and protein expression of genes involved in chemoresistance. We observed high cross-resistance to doxorubicin, vincristine, and paclitaxel in the cell lines resistant to these agents. We also found a significant correlation between resistance to these drugs and increased expression of P-gp. Two different mechanisms of topotecan resistance were observed in the W1TR and W1PR cell lines. We did not observe any correlation between MRP2 transcript and protein levels. Cell lines resistant to agents used in ovarian cancer treatment remained sensitive to methotrexate. The main mechanisms of drug resistance were due to P-gp expression in the doxorubicin, vincristine, and paclitaxel resistant cell lines and BCRP expression in the topotecan resistant cell line.

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