Anti-cancer effect of Indanone-based thiazolyl hydrazone derivative on colon cancer cell lines

Narayanan, Silpa; Gupta, Pranav; Nazim, Urooj; Ali, Mohsin; Karadkhelkar, Nishant; Ahmad, Mansoor; Chen, Zhe‐Sheng

doi:10.1016/j.biocel.2019.02.004

Cited by 36 publications

(33 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite of the advances in the CRC research field, which has indeed resulted in higher cure rates, this disease still remains a leading health challenge, consequently it is necessary to devote bigger efforts upon knowing the exact mechanism of CRC carcinogenesis, as well as to establish more significant strategies that contribute to their prevention and treatment (Narayanan et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Anti-proliferative bioactivity against HT-29 colon cancer cells of a withanolides-rich extract from golden berry (Physalis peruviana L.) calyx investigated by Foodomics

Ballesteros-Vivas

Álvarez-Rivera

León

et al. 2019

Journal of Functional Foods

View full text Add to dashboard Cite

A comprehensive Foodomics study was carried out in this work to investigate the changes induced at gene and metabolite expression levels on HT29 colon cancer cell lines upon treatment with a bioactives-enriched extract from goldenberry calyx. As a result of the proposed multi-omics approach, the tested extract induced transcriptional activation of pro-apoptotic genes, and altered the expression of several genes related to the oxidative stress response in treated cancer cells. Metabolomics data confirm altered cellular redox homeostasis, providing additional evidence to transcriptomic results. Foodomics data integration also revealed alteration on relevant metabolic processes, suggesting inactivation of aminoacyl tRNA charging pathway, dysfunction on carnitine shuttle and beta-oxidation of fatty acids, and pyrimidine ribonucleotide interconversion impairment. These observations are in line with functional analysis and anti-proliferative activity results, where the viability of HT-29 colon cancer cells was notably reduced after 48h treatment without affecting the viability of normal human colon fibroblast cells.

show abstract

Section: Introductionmentioning

confidence: 99%

Anti-proliferative bioactivity against HT-29 colon cancer cells of a withanolides-rich extract from golden berry (Physalis peruviana L.) calyx investigated by Foodomics

Ballesteros-Vivas

Álvarez-Rivera

León

et al. 2019

Journal of Functional Foods

View full text Add to dashboard Cite

show abstract

“…International Publisher leading to increased cases of relapse and mortality in NSCLC patients [5][6][7][8][9][10]. MDR or chemoresistance characterizes a phenomenon where cells exhibit resistance to drugs that are pharmacologically and structurally distinct [11][12][13][14][15].…”

Section: Ivyspringmentioning

confidence: 99%

“…Regardless of achieving substantial advancements in the treatment of metastatic or locally advanced NSCLC, improving the quality of life in NSCLC patients has been a major challenge 4 . Treatment modalities involving surgery, radiation therapy, and chemotherapy are considered essential to treat NSCLC patients but tumor heterogenicity and multidrug resistance (MDR) remain to be a primary obstacle by limiting chemotherapeutic efficacy leading to increased cases of relapse and mortality in NSCLC patients 5 - 10 . MDR or chemoresistance characterizes a phenomenon where cells exhibit resistance to drugs that are pharmacologically and structurally distinct 11 - 15 .…”

Section: Introductionmentioning

confidence: 99%

The Spleen Tyrosine Kinase Inhibitor, Entospletinib (GS-9973) Restores Chemosensitivity in Lung Cancer Cells by Modulating ABCG2-mediated Multidrug Resistance

Narayanan

Wang

et al. 2021

Int. J. Biol. Sci.

Self Cite

View full text Add to dashboard Cite

Tyrosine kinase inhibitors (TKIs) are important in managing lymphoid malignancies by targeting B-cell receptor signaling pathways. Entospletinib (GS-9973) is an oral, selective inhibitor of spleen tyrosine kinase (Syk), currently in the phase II clinical trials for the treatment of chronic lymphocytic leukemia. Syk is abundantly present in the cells of hematopoietic lineage that mediates cell proliferation, differentiation, and adhesion. In this current study, we evaluated the efficacy of GS-9973 to overcome multidrug resistance (MDR) due to the overexpression of the ABCG2 transporter in the non-small cell lung cancer (NSCLC) cell line, NCI-H460/MX20. In vitro , 3 μM of GS-9973 reversed the drug resistance of NCI-H460/MX20 cell line to mitoxantrone or doxorubicin. GS-9973, at 3 μM reverses ABCG2-mediated MDR by blocking ABCG2 efflux activity and downregulating ABCG2 expression at the protein level but did not alter the ABCG2 mRNA expression and subcellular localization of the ABCG2 protein compared to drug-resistant cells incubated with the vehicle. GS-9973 produced a moderate concentration-dependent increase in the ATPase activity of ABCG2 (EC 50 = 0.42 µM) and molecular docking data indicated that GS-9973 had a high affinity (-10.226 kcal/mol) for the substrate-binding site of ABCG2. Finally, HPLC analysis proved that the intracellular concentration of GS-9973 is not significantly different in both parental and resistant cell lines. In conclusion, our study suggests that in vitro , GS-9973 in combination with certain anticancer drugs, represent a strategy to overcome ABCG2-mediated MDR cancers.

show abstract

“…Cancer is the second main cause of death worldwide [ 1 , 2 ] and according to the World Health Organization, 1,762,450 new cases and around 606,880 cancer deaths have been disclosed in the United States [ 3 , 4 ]. Drug resistance in cancer cells can attenuate or abrogate the efficacy of anticancer drug treatment, thereby contributing to most cancer-related deaths [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. Colorectal cancer (CRC) has been identified as a common form of cancer [ 13 ] and although the FOLFIRI regimen (folinic acid, 5-fluorouracil, and irinotecan) increases the survival rate of metastatic CRC patients, only approximately 50% of patients show an objective response because of resistance to the treatment [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

VKNG-1 Antagonizes ABCG2-Mediated Multidrug Resistance via p-AKT and Bcl-2 Pathway in Colon Cancer: In Vitro and In Vivo Study

Narayanan

Fan

Gujarati

et al. 2021

Cancers

Self Cite

View full text Add to dashboard Cite

The emergence of multidrug resistance (MDR) to chemotherapeutic drugs is a major problem in the therapy of cancer. Knowledge of the mechanisms of drug resistance in cancer is necessary for developing efficacious therapies. ATP-binding cassette (ABC) transporters are transmembrane proteins that efflux chemotherapeutic drugs from cancer cells, thereby producing MDR. Our research efforts have led to the discovery of VKNG-1, a compound that selectively inhibits the ABCG2 transporter and reverses resistanctabe to standard anticancer drugs both in vitro and in vivo. VKNG-1, at 6 µM, selectively inhibited ABCG2 transporter and sensitized ABCG2-overexpressing drug-resistant cancer cells to the ABCG2 substrate anticancer drugs mitoxantrone, SN-38, and doxorubicin in ABCG2-overexpressing colon cancers. VKNG- 1 reverses ABCG2-mediated MDR by blocking ABCG2 efflux activity and downregulating ABCG2 expression at the mRNA and protein levels. Moreover, VKNG-1 inhibits the level of phosphorylated protein kinase B (PKB/p-AKT), and B-cell lymphoma-2 (Bcl-2) protein which may overcome resistance to anticancer drugs. However, the in vitro translocation of ABCG2 protein did not occur in the presence of 6 µM of VKNG-1. In addition, VKNG-1 enhanced the anticancer efficacy of irinotecan in ABCG2- overexpressing mouse tumor xenografts. Overall, our results suggest that VKNG-1 may, in combination with certain anticancer drugs, represent a treatment to overcome ABCG2-mediated MDR colon cancers.

show abstract

Anti-cancer effect of Indanone-based thiazolyl hydrazone derivative on colon cancer cell lines

Cited by 36 publications

References 41 publications

Anti-proliferative bioactivity against HT-29 colon cancer cells of a withanolides-rich extract from golden berry (Physalis peruviana L.) calyx investigated by Foodomics

Anti-proliferative bioactivity against HT-29 colon cancer cells of a withanolides-rich extract from golden berry (Physalis peruviana L.) calyx investigated by Foodomics

The Spleen Tyrosine Kinase Inhibitor, Entospletinib (GS-9973) Restores Chemosensitivity in Lung Cancer Cells by Modulating ABCG2-mediated Multidrug Resistance

VKNG-1 Antagonizes ABCG2-Mediated Multidrug Resistance via p-AKT and Bcl-2 Pathway in Colon Cancer: In Vitro and In Vivo Study

Contact Info

Product

Resources

About