Inhibiting ABCG2 could potentially enhance the efficacy of hypericin-mediated photodynamic therapy in spheroidal cell models of colorectal cancer

Khot, M. Ibrahim; Perry, Sarah L.; Maisey, Thomas; Armstrong, G; Andrew, Helen; Hughes, Tom; Kapur, Nikil; Jayne, David

doi:10.1016/j.pdpdt.2018.06.027

Cited by 26 publications

(25 citation statements)

References 42 publications

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“…For our experiments, the human colorectal adenocarcinoma cell line, HT29, was used to generate 3D spheroids. HT29 has been used extensively in 3D cell culturing based studies, and from previous multiple studies, we have found HT29 to form spheroidal cultures with relative ease [45][46][47][48] . As demonstrated in Figs.…”

Section: Discussionmentioning

confidence: 81%

Characterising a PDMS based 3D cell culturing microfluidic platform for screening chemotherapeutic drug cytotoxic activity

Khot

Levenstein

Boer

et al. 2020

Sci Rep

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Three-dimensional (3D) spheroidal cell cultures are now recognised as better models of cancers as compared to traditional cell cultures. However, established 3D cell culturing protocols and techniques are time-consuming, manually laborious and often expensive due to the excessive consumption of reagents. Microfluidics allows for traditional laboratory-based biological experiments to be scaled down into miniature custom fabricated devices, where cost-effective experiments can be performed through the manipulation and flow of small volumes of fluid. In this study, we characterise a 3D cell culturing microfluidic device fabricated from a 3D printed master. HT29 cells were seeded into the device and 3D spheroids were generated and cultured through the perfusion of cell media. Spheroids were treated with 5-Fluorouracil for five days through continuous perfusion and cell viability was analysed on-chip at different time points using fluorescence microscopy and Lactate dehydrogenase (LDH) assay on the supernatant. Increasing cell death was observed in the HT29 spheroids over the five-day period. The 3D cell culturing microfluidic device described in this study, permits on-chip anti-cancer treatment and viability analysis, and forms the basis of an effective platform for the high-throughput screening of anti-cancer drugs in 3D tumour spheroids.

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Section: Discussionmentioning

confidence: 81%

Characterising a PDMS based 3D cell culturing microfluidic platform for screening chemotherapeutic drug cytotoxic activity

Khot

Levenstein

Boer

et al. 2020

Sci Rep

Self Cite

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“…43,73,74 Studies by Mikešová et al (2013) noted that the combination of glutathione level and NAD(P)H/FAD redox status when combined with hypericin in CRC cancer cells affects its resistance to PDT. 89 Moreover, studies by Khot et al (2018), treated spheroidal CRC cell models with hypericin PDT and noted signicant resistance, with high expression levels of ABCG2 and suggested that possibly by inhibiting ABCG2 expression that this could potentially enhance the efficacy of hypericin-mediated PDT. 90 Additionally, studies by Halaburková et al (2017), reported enhanced CRC hypericin mediated PDT within in vitro cultured HT-29 cells using histone deacetylase inhibitors (HDACis) to sensitize CRC cells external stimuli to overcoming their resistance to hypericin by epigenetically reactivating the expression of CDKN1A.…”

Section: Photosensitizers For Pdd and Pdt Colorectal Cancer Applicationsmentioning

confidence: 99%

“…89 Moreover, studies by Khot et al (2018), treated spheroidal CRC cell models with hypericin PDT and noted signicant resistance, with high expression levels of ABCG2 and suggested that possibly by inhibiting ABCG2 expression that this could potentially enhance the efficacy of hypericin-mediated PDT. 90 Additionally, studies by Halaburková et al (2017), reported enhanced CRC hypericin mediated PDT within in vitro cultured HT-29 cells using histone deacetylase inhibitors (HDACis) to sensitize CRC cells external stimuli to overcoming their resistance to hypericin by epigenetically reactivating the expression of CDKN1A. 91 Studies by Montanha et al (2017) improved the water solubility of hypericin and its PDT effect within in vitro cultured Caco-2 and HT-29 CRC cells by encapsulating it in Pluronic P123 (P123).…”

Section: Photosensitizers For Pdd and Pdt Colorectal Cancer Applicationsmentioning

confidence: 99%

Photodynamic diagnosis and photodynamic therapy of colorectal cancer in vitro and in vivo

2020

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“…Previous studies have shown a selective accumulation of ALA-induced PpIX in oral potentially malignant disorders and malignant tissues, which is probably due to (1) limited capacity and/or low activity of ferrochelatase [ 15 ]; (2) differential PDT sensitivity in various cancer cell lines in combination with ABCG2 inhibition [ 16 ]. As ABCG2 has previously been shown to be critical for ALA-PDT in different human cancers, including brain and colorectal cancers [ 17 , 18 , 19 ], inhibition of ABCG2 could potentially enhance the efficacy of ALA-PDT in treatment of HNC.…”

Section: Introductionmentioning

confidence: 99%

Natural Compounds Modulate Drug Transporter Mediated Oral Cancer Treatment

Yang

Wei

Li³

et al. 2020

Biomolecules

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Oral cancer (OC) is a serious health problem. Surgery is the best method to treat the disease but might reduce the quality of life of patients. Photodynamic therapy (PDT) may enhance quality of life but with some limitations. Therefore, the development of a new strategy to facilitate PDT effectiveness has become crucial. ATP-binding cassette G2 (ABCG2) is a membrane protein-associated drug resistance and stemness in cancers. Here, we examined whether ABCG2 plays an important role in regulating the treatment efficacy of PDT and whether ABCG2 inhibition by natural compounds can promote the effect of PDT in OC cells. Several head and neck cancer cells were utilized in this study. OECM1 and SAS cells were selected to investigate the relationship between ABCG2 expression and protoporphyrin IX (PpIX) accumulation. Western blot analysis, flow cytometry analysis, and survival probability were performed to determine PDT efficacy and cellular stemness upon treatment of different dietary compounds, including epigallocatechin gallate (EGCG) and curcumin. In this study, we found that ABCG2 expression varied in OC cells. Hypoglycemic culture for SAS cells enhanced ABCG2 expression as higher ABCG2 expression was associated with lower PpIX accumulation and cellular stemness in OC cells. In contrast, suppression of ABCG2 expression by curcumin and tea polyphenol EGCG led to greater PpIX accumulation and enhanced PDT treatment efficiency in OC cells. In conclusion, ABCG2 plays an important role in regulating the effect of PDT. Change in glucose concentration and treatment with natural compounds modulated ABCG2 expression, resulting in altered PDT efficacy for OC cells. These modulations raise a potential new treatment strategy for early-stage OCs.

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Inhibiting ABCG2 could potentially enhance the efficacy of hypericin-mediated photodynamic therapy in spheroidal cell models of colorectal cancer

Abstract: Hypericin-PDT has reduced efficacy in CRC spheroids as compared to 2D cultures, which may be attributable through upregulation in ABCG2. The clinical efficacy of Hypericin-PDT may be enhanced by ABCG2 inhibition.

Cited by 26 publications

References 42 publications

Characterising a PDMS based 3D cell culturing microfluidic platform for screening chemotherapeutic drug cytotoxic activity

Characterising a PDMS based 3D cell culturing microfluidic platform for screening chemotherapeutic drug cytotoxic activity

Photodynamic diagnosis and photodynamic therapy of colorectal cancer in vitro and in vivo

Natural Compounds Modulate Drug Transporter Mediated Oral Cancer Treatment

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