The orally active pterocarpanquinone LQB‐118 exhibits cytotoxicity in prostate cancer cell and tumor models through cellular redox stress

Martino, Thiago; Kudrolli, Tarana A.; Kumar, Binod; Salviano, Ísis; Mencalha, André Luiz; Coelho, Marsen Garcia Pinto; Justo, Graça; Costa, Paulo R. R.; Sabino, K.C.C.; Lupold, Shawn E.

doi:10.1002/pros.23455

Cited by 11 publications

(7 citation statements)

References 39 publications

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“…Our previous studies demonstrated the cytotoxic activity of the synthetic LQB-118 compound in several types of cancer, including AML (25)(26)(27)(28)(29)(40)(41)(42)(43). Therefore, the present study aimed to investigate the antitumor effect of the LQB-118 compound particularly in cells resistant to cytarabine.…”

Section: Lqb-118 Exhibits Cytotoxicity Against Cytarabine-resistant C...mentioning

confidence: 96%

The pterocarpanquinone LQB‑118 compound induces apoptosis of cytarabine‑resistant acute myeloid leukemia cells

et al. 2021

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Acute myeloid leukemia (AML) is a complex hematological disorder characterized by blockage of differentiation and high proliferation rates of myeloid progenitors. Anthracycline and cytarabine-based therapy has remained the standard treatment for AML over the last four decades. Although this treatment strategy has increased survival rates, patients often develop resistance to these drugs. Despite efforts to understand the mechanisms underlying cytarabine resistance, there have been few advances in the field. The present study developed an in vitro AML cell line model resistant to cytarabine (HL-60R), and identified chromosomal aberrations by karyotype evaluation and potential molecular mechanisms underlying chemoresistance. Cytarabine decreased cell viability, as determined by MTT assay, and induced cell death and cell cycle arrest in the parental HL-60 cell line, as revealed by Annexin V/propidium iodide (PI) staining and PI DNA incorporation, respectively, whereas no change was observed in the HL-60R cell line. In addition, the HL-60R cell line exhibited a higher tumorigenic capacity in vivo compared with the parental cell line. Notably, no reduction in tumor volume was detected in mice treated with cytarabine and inoculated with HL-60R cells. In addition, western blotting revealed that the protein expression levels of Bcl-2, X-linked inhibitor of apoptosis protein (XIAP) and c-Myc were upregulated in HL-60R cells compared with those in HL-60 cells, along with predominant nuclear localization of the p50 and p65 subunits of NF-κB in HL-60R cells. Furthermore, the antitumor effect of LQB-118 pterocarpanquinone was investigated; this compound induced apoptosis, a reduction in cell viability and a decrease in XIAP expression in cytarabine-resistant cells. Taken together, these data indicated that acquired cytarabine resistance in AML was a multifactorial process, involving chromosomal aberrations, and differential expression of apoptosis and cell proliferation signaling pathways. Furthermore, LQB-118 could be a potential alternative therapeutic approach to treat cytarabine-resistant leukemia cells.

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Section: Lqb-118 Exhibits Cytotoxicity Against Cytarabine-resistant C...mentioning

confidence: 96%

The pterocarpanquinone LQB‑118 compound induces apoptosis of cytarabine‑resistant acute myeloid leukemia cells

et al. 2021

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“…Later, studies further confirm that miR-101-3p targets EZH2 and suppresses proliferation and migration of PCa cells [12,13]. After thoroughly reviewing published literature on PCa, we found that ten target genes including SOD1 [14], SUB1 [15], TIGAR [16], NR2F2 [17], RLIP76 [9], COX-2 [18], Glyoxalase 1 [19], ZEB1 [20], Slug [20] as well as EZH2 [11,13,21,22] were truly inhibited by miR-101-3p in PCa tissues or cells. Furthermore, we found that the target genes of miR-101-3p were enriched in many biological processes, such as positive regulation of transcription, intracellular signal transduction, protein autophosphorylation, activation of MAPKK activity.…”

Section: Discussionmentioning

confidence: 54%

Identification of potential targets of microRNA-101-3p in prostate cancer by bioinformatics analysis

Zhang¹,

Wang²,

Bai³

et al. 2019

Preprint

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Background: MiR-101-3p, a tumor suppressor, has been implicated as a tumor suppressor miRNA in multiple primary malignancies including prostate cancer (PCa). This study aimed to explore target genes and relevant signaling pathways regulated by microRNA-101-3p (miR-101-3p) for further researches in PCa with bioinformatics analysis. Results: 565 target genes were appeared in all databases and enriched in positive regulation of transcription, which were mainly enriched in axon guidance and MAPK pathway. Two important modules were detected from PPI network. Ten hub genes were selected, including MAPK1, PIKFYVE, EGFR, SMARCA4, TOP2B, GSK3B, FOS, RAC1, BCL2 and TAF1. After thoroughly reviewing published literature, we found that 10 target genes and six signaling pathways were truly inhibited by miR-101-3p in various tissues or cells; some of these verified targets were in accordance with our present prediction. Conclusion: This study demonstrated that miR-101-3p target hub genes, including MAPK1, PIKFYVE, EGFR, SMARCA4, TOP2B, GSK3B, FOS, RAC1, BCL2 and TAF1, might promote the development of PCa. However, further experiments are still required to confirm potential functions of these miR-101-3p target genes and pathways in PCa.

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“…Other studies demonstrated that high SOD expression correlates with colon tumor aggressiveness and with resistance to cytotoxic drugs and radiotherapy [ 50 ]. The loss of SOD1 expression by siRNA knockdown significantly increased prostate cell sensitivity to cytotoxic agents, confirming SOD1 participation in cellular response and resistance [ 51 ]. Some evidence has indicated SOD1 overexpression in cancers maintaining cellular ROS below the crucial threshold [ 52 ].…”

Section: Resultsmentioning

confidence: 99%

The Cytotoxic Effect of Copper (II) Complexes with Halogenated 1,3-Disubstituted Arylthioureas on Cancer and Bacterial Cells

Chrzanowska

Drzewiecka-Antonik

Dobrzyńska

et al. 2021

IJMS

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A series of eight copper (II) complexes with 3-(4-chloro-3-nitrophenyl)thiourea were designed and synthesized. The cytotoxic activity of all compounds was assessed in three human cancer cell lines (SW480, SW620, PC3) and human normal keratinocytes (HaCaT). The complexes 1, 3, 5, 7 and 8 were cytotoxic to the studied tumor cells in the low micromolar range, without affecting the normal cells. The complexes 1, 3, 7 and 8 induced lactate dehydrogenase (LDH) release in all cancer cell lines, but not in the HaCaT cells. They provoked early apoptosis in pathological cells, especially in SW480 and PC3 cells. The ability of compounds 1, 3, 7 and 8 to diminish interleukin-6 (IL-6) concentration in a cell was established. For the first time, the influence of the most promising Cu (II) complexes on intensities of detoxifying and reactive oxygen species (ROS) scavenging the enzymes of tumor cells was studied. The cytotoxic effect of all copper (II) conjugates against standard and hospital bacterial strains was also proved.

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The orally active pterocarpanquinone LQB‐118 exhibits cytotoxicity in prostate cancer cell and tumor models through cellular redox stress

Abstract: LQB-118 is a developing and orally active pterocarpanquinone agent that effectively kills PCa cells through quinone reduction and ROS generation. The inhibition SOD1 expression enhances LQB-118 activity, presumably by impairing the cellular antioxidant response.

Cited by 11 publications

References 39 publications

The pterocarpanquinone LQB‑118 compound induces apoptosis of cytarabine‑resistant acute myeloid leukemia cells

The pterocarpanquinone LQB‑118 compound induces apoptosis of cytarabine‑resistant acute myeloid leukemia cells

Identification of potential targets of microRNA-101-3p in prostate cancer by bioinformatics analysis

The Cytotoxic Effect of Copper (II) Complexes with Halogenated 1,3-Disubstituted Arylthioureas on Cancer and Bacterial Cells

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