Methylated chrysin reduced cell proliferation, but antagonized cytotoxicity of other anticancer drugs in acute lymphoblastic leukemia

Goto, Hiroaki; Yanagimachi, Masakatsu; Goto, Shoko; Takeuchi, Masanobu; Kato, Hiromi; Yokosuka, Tomoko; Kajiwara, Ryosuke; Yokota, Shumpei

doi:10.1097/cad.0b013e32834fb731

Cited by 15 publications

(13 citation statements)

References 28 publications

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“…DMF has been reported to induce apoptosis and suppress proliferation and cell growth in various pathological cell types including those of leukemia (Goto et al, ) and hepatocellular carcinoma (Yang et al, ) and adipocytes (Song, Kim, Kim, Kim, & Hwang, ). In the present study, DMF has been shown to consistently decrease proliferation and induce apoptosis in two endometriosis cell lines.…”

Section: Discussionmentioning

confidence: 99%

5,7‐Dimethoxyflavone induces apoptotic cell death in human endometriosis cell lines by activating the endoplasmic reticulum stress pathway

Park

Song

et al. 2020

Phytotherapy Research

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Endometriosis is a reproductive disorder characterized by the dislocation of endometrial tissues. Approximately 5–20% of women at their reproductive age are diagnosed with endometriosis, which causes chronic pain and infertility. Here, we demonstrated that the bioactive flavonoid, 5,7‐dimethoxyflavone (DMF), exhibited antiproliferative and apoptotic effects in VK2/E6E7 and End1/E6E7 cells which were established from vaginal and endocervical tissue taken from a premenopausal woman undergoing hysterectomy for endometriosis. DMF treatment significantly elevated DNA fragmentation resulting in apoptotic cell death in both cell lines. Furthermore, DMF induced loss of mitochondrial membrane potential, dysregulation of intracellular calcium level, and ROS production, which accelerate apoptosis. Additionally, DMF modulated the expression of the signaling molecules related to cell survival and endoplasmic reticulum stress in VK2/E6E7 and End1/E6E7 cells. Overall, DMF may ameliorate endometriosis and can be a potential alternative to hormonal and surgical therapy for endometriosis treatment.

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Section: Discussionmentioning

confidence: 99%

5,7‐Dimethoxyflavone induces apoptotic cell death in human endometriosis cell lines by activating the endoplasmic reticulum stress pathway

Park

Song

et al. 2020

Phytotherapy Research

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“…YCUB-5 (positive for CD10, CD13, CD19, and HLA-DR) has the abnormal karyotype with + x , +21. YCUB-8 established from a 13-year-old female has t (1;19) and is a relatively newly developed cell line [58,59] We therefore present anti-leukemic actions of individual polyphenols in each of these cell lines.…”

Section: Molecular Mechanisms Of Anti-leukemic Activities Of Indivmentioning

confidence: 99%

“…Exposure of YCUB-2 and YCUB-5 to 5 or 20 μg/mL for 24 h revealed accumulation of ROS in YCUB-5 cells, but not in YCUB-2 cells, hence, suggesting that DMF-induced growth inhibition was not through oxidative stress-dependent pathway. Treatment of YCUB-2, YCUB-5, and YCUB-6 cells with a combination of DMF and other anticancer drugs [4-hydroperoxy-cyclophosphamide (4HO-CY), cytarabin (AraC), l -asparaginase ( l -asp), or vincristine (VCR)] indicated that DMF exhibited antagonistic effects on all the tested drugs, it was therefore suggested by the authors that chrysin and its analog (DMF) should be used each as single therapeutic agents rather than in combination with other anticancer drugs [58]. …”

Section: Molecular Mechanisms Of Anti-leukemic Activities Of Indivmentioning

confidence: 99%

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A Review of Molecular Mechanisms of the Anti-Leukemic Effects of Phenolic Compounds in Honey

Abubakar

Abdullah

Sulaiman

et al. 2012

IJMS

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Hematologic malignancies constitute about 9% of all new cases of cancers as reported via the GLOBOCAN series by International Agency for Research on Cancer (IARC) in 2008. So far, the conventional therapeutic and surgical approaches to cancer therapy have not been able to curtail the rising incidence of cancers, including hematological malignancies, worldwide. The last decade has witnessed great research interest in biological activities of phenolic compounds that include anticancer, anti-oxidation and anti-inflammation, among other things. A large number of anticancer agents combat cancer through cell cycle arrest, induction of apoptosis and differentiation, as well as through inhibition of cell growth and proliferation, or a combination of two or more of these mechanisms. Various phenolic compounds from different sources have been reported to be promising anticancer agents by acting through one of these mechanisms. Honey, which has a long history of human consumption both for medicinal and nutritional uses, contains a variety of phenolic compounds such as flavonoids, phenolic acids, coumarins and tannins. This paper presents a review on the molecular mechanisms of the anti-leukemic activity of various phenolic compounds on cell cycle, cell growth and proliferation and apoptosis, and it advocates that more studies should be conducted to determine the potential role of honey in both chemoprevention and chemotherapy in leukemia.

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“…Teniposide was also included as it is administered to ALL patients with induction failure [27], [28]. cis-Resveratrol [29], Flavopiridol [30], PD0332991 [31], 3,3′-Diindolylmethane [32] and 5,7-Dimethoxyflavone [33] have also been observed to have toxic effects on leukemic cells in studies on ALL samples. The drugs Indirubin [34], AZD5438 [35], Bryostatin-1 [36] and CCT020312 [37], which have been reported to inhibit cell proliferation, were also tested against the cell cycle proteins investigated in our study.…”

Section: Methodsmentioning

confidence: 99%

Drug Targets for Cell Cycle Dysregulators in Leukemogenesis: In Silico Docking Studies

Jayaraman¹,

Jamil²

2014

PLoS ONE

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Alterations in cell cycle regulating proteins are a key characteristic in neoplastic proliferation of lymphoblast cells in patients with Acute Lymphoblastic Leukemia (ALL). The aim of our study was to investigate whether the routinely administered ALL chemotherapeutic agents would be able to bind and inhibit the key deregulated cell cycle proteins such as - Cyclins E1, D1, D3, A1 and Cyclin Dependent Kinases (CDK) 2 and 6. We used Schrödinger Glide docking protocol to dock the chemotherapeutic drugs such as Doxorubicin and Daunorubicin and others which are not very common including Clofarabine, Nelarabine and Flavopiridol, to the crystal structures of these proteins. We observed that the drugs were able to bind and interact with cyclins E1 and A1 and CDKs 2 and 6 while their docking to cyclins D1 and D3 were not successful. This binding proved favorable to interact with the G1/S cell cycle phase proteins that were examined in this study and may lead to the interruption of the growth of leukemic cells. Our observations therefore suggest that these drugs could be explored for use as inhibitors for these cell cycle proteins. Further, we have also highlighted residues which could be important in the designing of pharmacophores against these cell cycle proteins. This is the first report in understanding the mechanism of action of the drugs targeting these cell cycle proteins in leukemia through the visualization of drug-target binding and molecular docking using computational methods.

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Methylated chrysin reduced cell proliferation, but antagonized cytotoxicity of other anticancer drugs in acute lymphoblastic leukemia

Cited by 15 publications

References 28 publications

5,7‐Dimethoxyflavone induces apoptotic cell death in human endometriosis cell lines by activating the endoplasmic reticulum stress pathway

5,7‐Dimethoxyflavone induces apoptotic cell death in human endometriosis cell lines by activating the endoplasmic reticulum stress pathway

A Review of Molecular Mechanisms of the Anti-Leukemic Effects of Phenolic Compounds in Honey

Drug Targets for Cell Cycle Dysregulators in Leukemogenesis: In Silico Docking Studies

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