Benzophenones and xanthone derivatives from Garcinia schomburgkiana -induced P-glycoprotein overexpression in human colorectal Caco-2 cells via oxidative stress-mediated mechanisms

Boonyong, Cherdsak; Pattamadilok, Chutichot; Suttisri, Rutt; Jianmongkol, Suree

doi:10.1016/j.phymed.2017.01.011

Cited by 18 publications

(15 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Multidrug resistance (MDR) represents a main reason for chemotherapy failure. Among the most important MDR mechanisms are ATP binding cassette (ABC) proteins expressed on cancer cell membranes (Efferth, 2001; Gillet et al, 2007; Boonyong et al, 2017; Efferth and Volm, 2017; Umsumarng et al, 2017). BCRP belongs to this family of efflux transporters responsible for drug disposition and distribution.…”

Section: Introductionmentioning

confidence: 99%

Collateral Sensitivity of Parthenolide via NF-κB and HIF-α Inhibition and Epigenetic Changes in Drug-Resistant Cancer Cell Lines

2019

View full text Add to dashboard Cite

Parthenolide (PT) is a sesquiterpene lactone isolated from Tanacetum parthenium . In this study, PT showed varying cytotoxic effects against different solid tumor cell lines. HCT116 (p53 +/+ ) colon carcinoma cells and their parental HCT116 knockout p53 (p53 -/- ) cell lines showed a resistance degree of 2.36. On the other hand, wild-type U87.MG cells or cells transfected with a deletion-activated EGFR cDNA (U87.MGΔEGFR) exhibited slight sensitivity toward PT. Multidrug-resistant MDA-MB-231-BCRP cells were even more sensitive toward PT than sensitive MDA-MB-231-pcDNA cells with a resistance degree of 0.07 (collateral sensitivity). To the best of our knowledge, hypersensitivity (collateral sensitivity) in MDA-MB-231-BCRP cell line is reported in this study for the first time. We attempted to identify the mechanism of collateral sensitivity. Firstly, we found that PT bound to IKK preventing IκBα degradation and eventually inhibition of the nuclear factor kappa B (NF-κB) pathway. Down-regulation of hypoxia inducing factor 1-alpha (HIF-1α) in MDA-MB-231-BCRP resistant cells may be a second mechanism, since it is a target gene of NF-κB. Moreover, PT also showed epigenetic effect by inhibition of HDAC activity as shown using both molecular docking and HDAC activity assay. Based on COMPARE and hierarchical cluster analyses, we found gene expression profiles that predicted sensitivity or resistance of 47 tumor cell lines toward PT. Interestingly, pathway analyses of gene expression profiles revealed NF-κB and HIF signaling as top networks of these genes, cellular functions and canonical pathways influencing the activity of PT against tumor cells. In conclusion, PT exerted profound cytotoxic activity against various cancer cell lines mainly against BCRP-overexpressing tumor cells, suggesting PT as novel candidate for cancer treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

Collateral Sensitivity of Parthenolide via NF-κB and HIF-α Inhibition and Epigenetic Changes in Drug-Resistant Cancer Cell Lines

2019

View full text Add to dashboard Cite

show abstract

“…doxorubicin, daunorubicin, epirubicin, idarubicin) [ 8 ]. Numerous inhibitors have been identified for P-glycoprotein’s efflux function [ 11 – 13 ]. Another well-known MDR-conferring ABC transporter is the breast cancer resistance protein ( ABCG2/ BCRP).…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity of nimbolide towards multidrug-resistant tumor cells and hypersensitivity via cellular metabolic modulation

et al. 2018

View full text Add to dashboard Cite

Nimbolide is considered a promising natural product in cancer prevention and treatment. However, it is not known yet, whether the different mechanisms of multidrug resistance (MDR) influence its anticancer activity. In this study, well-known MDR mechanisms (ABCB1, ABCG2, ABCB5, TP53, EGFR) were evaluated against nimbolide. The P-glycoprotein (ABCB1/MDR1)-overexpressing CEM/ADR5000 cell line displayed remarkable hypersensitivity to nimbolide, which was mediated through upregulation of the tumor suppressor, PTEN, and its downstream components resulted in significant downregulation in ABCB1/MDR1 mRNA and P-glycoprotein. In addition, nimbolide targeted essential cellular metabolic-regulating elements including HIF1α, FoxO1, MYC and reactive oxygen species. The expression of breast cancer resistance protein (BCRP) as well as epidermal growth factor receptor (EGFR) and mutant tumor suppressor TP53 did not correlate to nimbolide’s activity. Furthermore, this paper looked for other molecular determinants that might determine tumor cellular response towards nimbolide. COMPARE and hierarchical cluster analyses of transcriptome-wide microarray-based mRNA expressions of the NCI 60 cell line panel were performed, and a set of 40 genes from different functional groups was identified. The data suggested NF-κB as master regulator of nimbolide’s activity. Interestingly, HIF1α was determined by COMPARE analysis to mediate sensitivity to nimbolide, which would be of great benefit in targeted therapy.

show abstract

“…Our findings might be supported by previous studies that linked the increase in ROS levels in Caco-2 cells after different cytotoxic drug administrations with ROS-induced resistance to these treatments. 46 Moreover, probably, this enhancing effect of each liposomal drug monotherapy on tumor oxidative stress could be an explanation for lower antitumor activity of the combined therapy based on the sequential administration of the liposomal formulations compared with the antitumor activity of that based on their simultaneous administration (Fig. 2).…”

Section: Discussionmentioning

confidence: 99%

Liposomal prednisolone phosphate potentiates the antitumor activity of liposomal 5-fluorouracil in C26 murine colon carcinomain vivo

Pătraș

Sylvester

Lupuţ

et al. 2017

Cancer Biology & Therapy

View full text Add to dashboard Cite

The antitumor efficacy of 5-fluorouracil (5-FU) in advanced colorectal cancer (CRC) is hindered not only by the low therapeutic index, but also by tumor cell resistance to this cytotoxic drug. Therefore, to enhance the 5-FU antitumor activity, the present research used a novel tumor-targeted therapy based on the co-administration of 5-FU encapsulated in long-circulating liposomes (LCL-5-FU) together with liposomal prednisolone phosphate (LCL-PLP), a formulation with known anti-angiogenic actions on C26 murine colon carcinoma cells. Thus, we assessed the in vivo effects of the combined liposomal drug therapy on C26 carcinoma growth as well as on the production of molecular markers with key roles in tumor development such as angiogenic, inflammatory, and oxidative stress molecules. To get further insight into the polarization state of tumor microenvironment after the treatment, we determined the IL-10/IL-12p70 ratio in tumors. Our results showed that combined liposomal drug therapy inhibited almost totally tumor growth and was superior as antitumor activity to both single liposomal drug therapies tested. The antitumor efficacy of the combined therapy was mainly related to the anti-angiogenic and anti-inflammatory actions on C26 carcinoma milieu, being favored by its controlling effect on intratumor oxidative stress and the skewing of polarization of tumor microenvironmental cells toward their antineoplastic phenotypes. Thus, our study unveils a promising treatment strategy for CRC that should be furthermore considered.

show abstract

Benzophenones and xanthone derivatives from Garcinia schomburgkiana -induced P-glycoprotein overexpression in human colorectal Caco-2 cells via oxidative stress-mediated mechanisms

Cited by 18 publications

References 34 publications

Collateral Sensitivity of Parthenolide via NF-κB and HIF-α Inhibition and Epigenetic Changes in Drug-Resistant Cancer Cell Lines

Collateral Sensitivity of Parthenolide via NF-κB and HIF-α Inhibition and Epigenetic Changes in Drug-Resistant Cancer Cell Lines

Cytotoxicity of nimbolide towards multidrug-resistant tumor cells and hypersensitivity via cellular metabolic modulation

Liposomal prednisolone phosphate potentiates the antitumor activity of liposomal 5-fluorouracil in C26 murine colon carcinomain vivo

Contact Info

Product

Resources

About