A new nanostructured carrier design including oil to enhance the pharmaceutical properties of retinoid therapy and its therapeutic effects on chemo-resistant ovarian cancer

Narvekar, Mayuri; Xue, Hui; Tran, Ngoc; Mikhael, Mariam; Wong, Ho Lun

doi:10.1016/j.ejpb.2014.04.014

Cited by 25 publications

(6 citation statements)

References 29 publications

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“…The resistance to ATRA may also be as a result of poor delivery of ATRA into ovarian cancer cells due to its high lipophilic nature or the length of treatment [41, 42]. Interestingly, although there were no effects of ATRA treatment on cell proliferation and apoptosis of SKOV-3 cells in previous studies [28, 39], a recent study by Narvekar et al (2014) showed ATRA’s pharmaceutical properties could be enhanced by polymer-oil nanostructured carriers in SKOV-3 cells [41]. Oil-soluble ATRA treatment molecules easily permeate across the cell membrane, induced apoptotic cell death and a long-term anti-tumorigenic effect in SKOV-3 cells [41].…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, although there were no effects of ATRA treatment on cell proliferation and apoptosis of SKOV-3 cells in previous studies [28, 39], a recent study by Narvekar et al (2014) showed ATRA’s pharmaceutical properties could be enhanced by polymer-oil nanostructured carriers in SKOV-3 cells [41]. Oil-soluble ATRA treatment molecules easily permeate across the cell membrane, induced apoptotic cell death and a long-term anti-tumorigenic effect in SKOV-3 cells [41]. Oil soluble formations of ATRA may improve effectiveness of the delivery of ATRA in ovarian cancer cells and should be further evaluated.…”

Section: Discussionmentioning

confidence: 99%

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Anti-tumour effects of all-trans retinoid acid on serous ovarian cancer

Lokman

Gunasegaran

et al. 2019

J Exp Clin Cancer Res

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BackgroundAnnexin A2 is increased in serous ovarian cancer and plays an essential role in ovarian cancer invasion and metastasis. In combination with S100A10, annexin A2 plays an important role in the plasminogen activator system regulating plasmin production. The aim of this study was to investigate the potential utility of all-trans retinoid acid (ATRA), an inhibitor of the annexin A2-S100A10 signalling pathway, as a new therapeutic against serous ovarian cancer.MethodsIn this study we determined the effects of ATRA treatment (1-5 μM) on annexin A2 and S100A10 expression, plasmin activation, and the ability of ATRA to inhibit serous ovarian cancer cell survival, motility and invasion in vitro. We also employed an ex vivo tissue explant assay to assess response to ATRA treatment in serous ovarian cancers. Cryopreserved serous ovarian cancer tissues were cultured on gelatin sponges for 72 h with ATRA (1 μM). Effects on apoptosis and proliferation were assessed by immunohistochemistry using antibodies to cleaved caspase 3 or Ki67, respectively.ResultsSurvival of serous ovarian cancer cells (OVCAR-3, OV-90, & OAW28) was significantly decreased by ATRA treatment (1-5 μM). ATRA (1 μM) also significantly decreased proliferation (Ki67 positivity, p = 0.0034), S100A10 protein levels (p = 0.0273), and increased cell apoptosis (cleaved caspase-3 positivity, p = 0.0024) in serous ovarian cancer tissues using the ex vivo tissue explant assay. In OAW28 cells, reduced cell survival following ATRA treatment was associated with a reduction of S100A10 mRNA and protein levels, S100A10 and annexin A2 membrane localization, plasmin generation, motility and invasion. In contrast, ATRA inhibited OV-90 cell survival and invasion but did not affect plasmin activation or S100A10 and annexin A2 expression or membrane localization.ConclusionsThese findings suggest that ATRA inhibits serous ovarian cancer proliferation and invasion via both S100A10 dependant and S100A10 independent mechanisms. Our results show that ATRA has promising potential as a novel therapy against serous ovarian cancer that warrants further evaluation.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-1017-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Anti-tumour effects of all-trans retinoid acid on serous ovarian cancer

Lokman

Gunasegaran

et al. 2019

J Exp Clin Cancer Res

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“…Narvekar and coworkers constructed Polymer-Oil Nanostructured Carriers (PONCs) where ATRA is dispersed in the oil phase within the polymeric matrix. These studies showed that ATRA-oil droplets efficiently permeated the lipid bilayer of the plasma membrane compared to the free drug, probably due to the ability of oil in promoting drug uptake into the cancer cells, thus increasing its permeation across the lipid membrane [152].…”

Section: Cellular Uptake and Endosomal Escapementioning

confidence: 99%

Current Trends in ATRA Delivery for Cancer Therapy

et al. 2020

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All-Trans Retinoic Acid (ATRA) is the most active metabolite of vitamin A. It is critically involved in the regulation of multiple processes, such as cell differentiation and apoptosis, by activating specific genomic pathways or by influencing key signaling proteins. Furthermore, mounting evidence highlights the anti-tumor activity of this compound. Notably, oral administration of ATRA is the first choice treatment in Acute Promyelocytic Leukemia (APL) in adults and NeuroBlastoma (NB) in children. Regrettably, the promising results obtained for these diseases have not been translated yet into the clinics for solid tumors. This is mainly due to ATRA-resistance developed by cancer cells and to ineffective delivery and targeting. This up-to-date review deals with recent studies on different ATRA-loaded Drug Delivery Systems (DDSs) development and application on several tumor models. Moreover, patents, pre-clinical, and clinical studies are also reviewed. To sum up, the main aim of this in-depth review is to provide a detailed overview of the several attempts which have been made in the recent years to ameliorate ATRA delivery and targeting in cancer.

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“…ATRA was incorporated in the NLCs for treatment of chemo-resistant ovarian cancer. 6 ATRA controls cancer progression with its unique cell-differentiating, anti-proliferative and apoptosis inducing activities mediated by the retinoic acid receptors and retinoid X receptors. 7 This drug is therefore officially approved for the treatment of acute promyelocytic leukemia, a subtype of blood cancer.…”

Section: Nanostructured Lipid Carriers (Nlcs)mentioning

confidence: 99%

Cancer research and therapy: Where are we today?

Sawant

Shegokar

2014

Int J Cancer Ther Oncol

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Till date scientists are struggling to understand the complete mechanism of carcinogenesis. In future, the real time detection of cancer may help scientists to identify some of the complicated biological mechanisms. Certain special features of cancer cells enable researchers to deliver the drug or to develop the right drug therapy. These cell properties include over expression or over activity in uptake of certain nutrients e.g. folic acid and increased permeability. Listed properties might vary depending upon the type of cancer and can be fully exploited by using nanoparticles either to detect the site of cancer or to direct the drug at the affected site. Product approach like drug conjugates, complexes serves as a good platform to solve issues like solubility, toxicity, poor penetration and stability related to cancer drugs. Beside this, several drug delivery platforms are under development by researchers in academia as well as in industry to deliver therapeutic molecules and new chemical entities to the targeted site in body. Amongst them, nanotechnology both at molecular and supramolecular level is a leading platform and can help to image, detect and treat cancer. Surface modification of nanoparticles by coating or anchoring their surface with special markers, materials, peptide, proteins, antibodies or antigens add extra feature and thereby can enhance the effectiveness. These treatments can be used individually or in combined form. In this review, advances on nanotechnological platform are discussed together with some assisting techniques like magnetic field, photo or light field, sonic rays are touched upon. New biological therapies that are advancing in this direction include the antisense therapy, cell therapy, gene therapy, radiation therapy and SiRNA interfaces which are discussed in brief in this article. This article gives short overview on use of complementary and alternative medicine for treatment of cancer such as traditional Chinese medicine (TCM), Ayurveda to avoid toxic effects of synthetic drugs.

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A new nanostructured carrier design including oil to enhance the pharmaceutical properties of retinoid therapy and its therapeutic effects on chemo-resistant ovarian cancer

Cited by 25 publications

References 29 publications

Anti-tumour effects of all-trans retinoid acid on serous ovarian cancer

Anti-tumour effects of all-trans retinoid acid on serous ovarian cancer

Current Trends in ATRA Delivery for Cancer Therapy

Cancer research and therapy: Where are we today?

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