Effect of Curcumin on Lung Resistance-Related Protein (LRP) in Retinoblastoma Cells

Thiyagarajan, Seethalakshmi; Thirumalai, Karthiyayini; Nirmala, S; Biswas, Jyotirmay; Krishnakumar, Subramanian

doi:10.3109/02713680903125329

Cited by 16 publications

(15 citation statements)

References 20 publications

(23 reference statements)

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“…In our earlier study, we have performed MTT assay to determine the relative cytotoxicity of curcumin in the Y79 RB cell line (data not shown; [30]). The concentrations that were less toxic to cells were chosen for further experiments.…”

Section: Discussionmentioning

confidence: 99%

In vitro and In silico studies on inhibitory effects of curcumin on multi drug resistance associated protein (MRP1) in retinoblastoma cells

Sreenivasan¹,

Ravichandran²,

Vetrivel³

et al. 2012

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Multi Drug Resistance (MDR) is one of the major causes of chemotherapy failure in human malignancies. Curcumin, the active constituent of Curcuma longa is a proven anticancer agent potentially modulating the expression and function of these MDR proteins. In this study, we attempted to test curcumin for its potential to inhibit the expression and function of multidrug resistance associated protein 1 (MRP1) in retinoblastoma (RB) cell lines through western blot, RT-PCR and functional assays. In silico analysis were also performed to understand the molecular interactions conferred by curucmin on MRP1 in RB cells. Western blot and RTPCR analysis did not show any correlation of MRP1 expression with increase in concentration of curcumin. However, inhibitory effect of curcumin on MRP1 function was observed as a decrease in the efflux of fluorescent substrate. Moreover, Curcumin did not affect 8-azido-ATP-biotin binding to MRP1 and it also showed inhibition of ATP-hydrolysis stimulated by quercetin, which is indicative of curcumin's interaction with the substrate binding site of MRP1. Furthermore, homology modelling and docking simulation studies of MRP1 also provided deeper insights into the molecular interactions, thereby inferring the potential binding mode of curcumin into the substrate binding site of MRP1.

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Section: Discussionmentioning

confidence: 99%

In vitro and In silico studies on inhibitory effects of curcumin on multi drug resistance associated protein (MRP1) in retinoblastoma cells

Sreenivasan¹,

Ravichandran²,

Vetrivel³

et al. 2012

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“…[184] Another study has suggested that curcumin blocks proteins involved with multidrug resistance in the Y79 cell line. [185] Co-administration of curcumin with other chemotherapy agents may, like cyclosporine, act as a chemosensitizer to improve retinoblastoma cell sensitivity to chemotherapy. [185] However, the use of antioxidants must be very cautiously considered in combination therapies for retinoblastoma, as generation of reactive oxygen species (ROS) to increase cellular oxidative-stress has been implicated as an important mechanism of action for many of the novel agents recently investigated.…”

Section: In Vitro Testingmentioning

confidence: 99%

Progress in Small Molecule Therapeutics for the Treatment of Retinoblastoma

Pritchard¹,

Dyer

Guy

2016

MRMC

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While mortality is low for intraocular retinoblastoma patients in the developed world who receive aggressive multimodal therapy, partial or full loss of vision occurs in approximately 50% of patients with advanced bilateral retinoblastoma. Therapies that preserve vision and reduce late effects are needed. Because clinical trials for retinoblastoma are difficult due to the young age of the patient population and relative rarity of the disease, robust preclinical testing of new therapies is critical. The last decade has seen advances towards identifying new therapies including the development of animal models of retinoblastoma for preclinical testing, progress in local drug delivery to reach intraocular targets, and improved understanding of the underlying biological mechanisms that give rise to retinoblastoma. This review discusses advances in these areas, with a focus on discovery and development of small molecules for the treatment of retinoblastoma, including novel targeted therapeutics such as inhibitors of the MDMX-p53 interaction (nutlin-3a), histone deacetylase (HDAC) inhibitors, and spleen tyrosine kinase (SYK) inhibitors.

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“…The protein is encoded by LRP gene and mechanism of action of this protein in eliciting MDR is yet to be explored. It has been investigated intensively that, these two proteins (MRP-1 and LRP) are solely associated with multidrug resistance in retinoblastoma [6], [7]. Thus, considering the relative importance of MDR in retinoblastoma, there is an urgent call for effective therapeutic strategy in retinoblastoma therapy.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, Thiyagarajan et al . have explored that; curcumin can down regulate the expression of LRP protein and mRNA in a concentration dependent manner in Y79 retinoblastoma cell line [7]. Additionally, curcumin has potent anticancer properties as demonstrated in a plethora of human cancer cell line and animal carcinogenesis model [14].…”

Section: Introductionmentioning

confidence: 99%

Folate Decorated Dual Drug Loaded Nanoparticle: Role of Curcumin in Enhancing Therapeutic Potential of Nutlin-3a by Reversing Multidrug Resistance

Das

Sahoo

2012

PLoS ONE

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Retinoblastoma is the most common intraocular tumor in children. Malfunctioning of many signaling pathways regulating cell survival or apoptosis, make the disease more vulnerable. Notably, resistance to chemotherapy mediated by MRP-1, lung-resistance protein (LRP) is the most challenging aspect to treat this disease. Presently, much attention has been given to the recently developed anticancer drug nutlin-3a because of its non-genotoxic nature and potency to activate tumor suppressor protein p53. However, being a substrate of multidrug resistance protein MRP1 and Pgp its application has become limited. Currently, research has step towards reversing Multi drug resistance (MDR) by using curcumin, however its clinical relevance is restricted by plasma instability and poor bioavailability. In the present investigation we tried to encapsulate nutlin-3a and curcumin in PLGA nanoparticle (NPs) surface functionalized with folate to enhance therapeutic potential of nutlin-3a by modulating MDR. We document that curcumin can inhibit the expression of MRP-1 and LRP gene/protein in a concentration dependent manner in Y79 cells. In vitro cellular cytotoxicity, cell cycle analysis and apoptosis studies were done to compare the effectiveness of native drugs (single or combined) and single or dual drug loaded nanoparticles (unconjugated/folate conjugated). The result demonstrated an augmented therapeutic efficacy of targeted dual drug loaded NPs (Fol-Nut-Cur-NPs) over other formulation. Enhanced expression or down regulation of proapoptotic/antiapoptotic proteins respectively and down-regulation of bcl2 and NFκB gene/protein by Fol-Nut-Cur-NPs substantiate the above findings. This is the first investigation exploring the role of curcumin as MDR modulator to enhance the therapeutic potentiality of nutlin-3a, which may opens new direction for targeting cancer with multidrug resistance phenotype.

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Effect of Curcumin on Lung Resistance-Related Protein (LRP) in Retinoblastoma Cells

Abstract: These results demonstrate that curcumin modulated the expression of LRP in the Y79 retinoblastoma cell line. Thus, curcumin may be used as a chemosensitizer to make the retinoblastoma cells more sensitive to the effects of chemotherapy.

Cited by 16 publications

References 20 publications

In vitro and In silico studies on inhibitory effects of curcumin on multi drug resistance associated protein (MRP1) in retinoblastoma cells

In vitro and In silico studies on inhibitory effects of curcumin on multi drug resistance associated protein (MRP1) in retinoblastoma cells

Progress in Small Molecule Therapeutics for the Treatment of Retinoblastoma

Folate Decorated Dual Drug Loaded Nanoparticle: Role of Curcumin in Enhancing Therapeutic Potential of Nutlin-3a by Reversing Multidrug Resistance

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