Flavonoids from Orostachys Japonicus A. Berger Induces Caspase-dependent Apoptosis at Least Partly through Activation of p38 MAPK Pathway in U937 Human Leukemic Cells

Lee, Won Sup; Yun, Jeong Won; Nagappan, Arulkumar; Jung, Ji Hyun; Yi, Sang Mi; Kim, Dong Hoon; Kim, Hye Jung; Kim, Gon‐Sup; Ryu, Chung Ho; Shin, Sung Chul; Hong, Soon Chan; Choi, Yung Hyun; Jung, Jin‐Myung

doi:10.7314/apjcp.2015.16.2.465

Cited by 15 publications

(15 citation statements)

References 20 publications

(21 reference statements)

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“…In previous studies, Icariside II sensitizes U937 cells to apoptosis by targeting STAT3-related signaling ( 35 ). and flavonoids extracted from Orostachys japonicus A. Berger (FEOJ) triggered caspase-dependent apoptosis of U937 cells through p38 MAPK signaling pathway ( 21 ). Further investigation focusing on the precise molecular mechanisms by which PTFC trigger U937 cell apoptosis should yield interesting results.…”

Section: Discussionmentioning

confidence: 99%

“…Flavonoids are naturally-occurring non-toxic material found widely in the plant kingdom, most of which have a wide range of biological activities. Exposure to flavonoids seems to reduce the risk for developing cancers ( 15 – 21 ). However, not much is known regarding the anti-cancer effects of pure total flavonoid compounds (PTFCs) extracted from the peel of Citrus paradisi Macfad, and the molecular mechanisms of its action are poorly understood in human cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of X‑linked inhibitor of apoptosis protein enhances anti‑tumor potency of pure total flavonoids on the growth of leukemic cells

Zhang

Lin

et al. 2017

Exp Ther Med

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Flavonoids, a vast group of polyphenols widely distributed in plants, are known to possess a range of biological activities and potential anti-tumor effects. X-linked inhibitor of apoptosis protein (XIAP) promotes the progression of leukemia by preventing tumor cells undergoing apoptosis. The present study investigated the potential effects and underlying mechanisms of pure total flavonoids from Citrus paradisi Macfad (PTFC) on human U937 cells, and explored the effects of short hairpin (sh)RNA-mediated XIAP knockdown on the anti-cancer effects of PTFC. Western blotting was used to determine level of apoptosis-associated effectors following PTFC treatment. A lentiviral vector of RNA interference of XIAP gene was constructed to downregulate XIAP expression. MTT assay and flow cytometry were used to determine the effects of PTFC separately or combined with XIAP-shRNA on inhibition and apoptosis of U937 cells, respectively. Treatment with PTFC effectively inhibited leukemic cell proliferation in a dose- and time-dependent manner. PTFC induced apoptosis of U937 cells in a dose-dependent manner, at a particular concentration range, by decreasing XIAP expression levels and activating caspases-3, −7 and −9. PTFC treatment combined with XIAP-shRNA additionally demonstrated a marked increase in cell apoptosis, compared with PTFC or XIAP-shRNA alone (P<0.05). Therefore, these findings suggest that PTFC inhibits growth and induces apoptosis in U937 cells in vitro. Furthermore, suppression of XIAP expression enhances these effects.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibition of X‑linked inhibitor of apoptosis protein enhances anti‑tumor potency of pure total flavonoids on the growth of leukemic cells

Zhang

Lin

et al. 2017

Exp Ther Med

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“…In the below (Table ), we have cited some of the very noteworthy flavonoids, such as quercetin (X. X. Chen et al, ; G. L. Russo et al, ), luteolin (Sak et al, ), gardenin B (Cabrera et al, ), hespertin and fisetin (Adan & Baran, ), myricetin (Ko et al, ), wogonin (H. W. Zhang et al, ), flavopiridol (Bright et al, ), vitexin inspired (Ling et al, ), sophoraflavanone G (Z. Y. Li et al, ), flavokawin B (Tang et al, ), kaempferol (K. Y. Kim et al, ), chrysin (Zaric et al, ), butein (Woo et al, ), naringenin (R. F. Li et al, ), catechin (L. Zhang et al, ), genistein (I. G. Kim et al, ), apigenin (Gonzalez‐Mejia et al, ; Jayasooriya et al, ), dorsmanin F (Kuete et al, ), astilbin (H. W. Yi et al, ), EGCG (Annabi et al, ; J. H. Jung et al, ), icaraside (Kang et al, ), phloridzin (Arumuggam et al, ), isochamaejasmin (S. D. Zhang et al, ), MF derivatives (Wudtiwai et al, ), icaritin (Q. Li et al, ), FEOJ (W. S. Lee et al, ), casticin (Kikuchi et al, ), chalcone (Mori et al, ), deguelin (S. Yi et al, ), morin (C. Park et al, ), medicarpin (Gatouillat et al, ), Antho 50 (Alhosin et al, ), rotenone (Estrella‐Parra et al, ), glabridin (H. L. Huang et al, ), hispidulin (H. Gao et al, ), oroxylin A (Hui et al, ), rhamnazin (Philchenkov & Zavelevych, ), wogonoside (Y. Chen et al, ), 7,8‐dihydroxyflavone hydrate (7,8‐DHF; H. Y. Park et al, ), panduratin A (Choi, Kim, & Hwang, ), silibinin (Pesakhov, Khanin, Studzinski, & Danilenko, ), galangin (Tolomeo et al, ), 2′‐nitroflavone (Cardenas, Blank, Marder, & Roguin, ), propolis (Eom, Lee, Yoon, & Yoo, ), tomentodiplacone B (Kollar, Barta, Zavalova, Smejkal, & Hampl, ), tamarixetin (Nicolini et al, ), phloretin (Kobori, Iwashita, Shinmoto, & Tsushida, ), a...…”

Section: Flavonoids Functional Mechanisms In Leukemia Cellsmentioning

confidence: 99%

“…Li et al, 2016), flavokawin B , kaempferol (K. Y. Kim et al, 2016), chrysin (Zaric et al, 2015), butein (Woo et al, 2016), naringenin (R. F. Li et al, 2015), catechin (L. Zhang et al, 2014), genistein (I. G. Kim et al, 2014), apigenin (Gonzalez-Mejia et al, 2010;Jayasooriya et al, 2012), dorsmanin F (Kuete et al, 2015), astilbin (H. W. Yi et al, 2008), EGCG (Annabi et al, 2007;, icaraside ), phloridzin (Arumuggam et al, 2017), isochamaejasmin (S. D. Zhang et al, 2015, MF derivatives (Wudtiwai et al, 2011), icaritin (Q. Li et al, 2013, FEOJ (W. S. Lee et al, 2015), casticin (Kikuchi et al, 2013), chalcone , deguelin (S. Yi et al, 2015), morin (C. Park et al, 2014), medicarpin (Gatouillat et al, 2015), Antho 50 (Alhosin et al, 2015), rotenone (Estrella-Parra et al, 2014), glabridin (H. L. , hispidulin (H. , oroxylin A (Hui et al, 2016), rhamnazin (Philchenkov & Zavelevych, 2015), wogonoside (Y. Chen et al, 2013) (Nicolini et al, 2014), phloretin (Kobori, Iwashita, Shinmoto, & Tsushida, 1999), and xanthohumol (Lust et al, 2005) with their chief working mechanisms in leukemia cells.…”

Section: Inhibition Of Survival Involved Signaling Pathwaysmentioning

confidence: 99%

Leukemia therapy by flavonoids: Future and involved mechanisms

Saraei

Marofi

Naimi

et al. 2018

Journal Cellular Physiology

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Flavonoids are a varied family of phytonutrients (plant chemicals) usually are detected in fruits and vegetables. In this big family, there exist more than 10,000 members that is separated into six chief subtypes: isoflavonols, flavonoenes, flavones, flavonols, anthocyanins, and chalcones. The natural compounds, such as fruits, have visible positive effects in regulating of survival involved signaling pathways that performance as the regulator of cell survival, growth, and proliferation. Researchers have established that commonly consumption up flavonoids decreases incidence and development risk of certain cancers, especially leukemia. Flavonoids have been able to induce apoptosis and stimulate cell cycle arrest in cancer cells via different pathways. Similarly, they have antiangiogenesis and antimetastasis capability, which were shown in wide ranges of cancer cells, particularly, leukemia. It seems that flavonoid because of their widespread approval, evident safety and low rate of side effects, have hopeful anticarcinogenic potential for leukemia therapy. Based on the last decade reports, the most important acting mechanisms of these natural compounds in leukemia cells are stimulating of apoptosis pathways by upregulation of caspase 3, 8, 9 and poly ADP‐ribose polymerase (PARP) and proapoptotic proteins, particularly Bax activation. As well, they can induce cell cycle arrest in target cells not only via increasing of activated levels of p21 and p53 but also by inhibition of cyclins and cyclin‐dependent kinases. Furthermore, attenuation of neclear factor‐κB and signal transducer and activator of transcription 3 activation, suppression of signaling pathway and downregulation of intracellular antiapoptotic proteins are other significant antileukemic function mechanism of flavonoids. Overall, it appears that flavonoids are promising and effective compounds in the field of leukemia therapy. In this review, we tried to accumulate and revise most promising flavonoids and finally declared their major working mechanisms in leukemia cells.

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“…Orostachys japonicus (O. japonicus) extracts have shown various biological activities including anti-inflammatory 20 , neuroprotective 21 , anti-ulcerative 22 , anti-oxidant 23 , and anti-tumor effects [24][25][26] . Particularly, it has been recognized as a potential anti-tumor treatment for a variety of tumor cells in Korea.…”

Section: Introductionmentioning

confidence: 99%

Orostachys japonicus DW and EtOH Extracts Induce Apoptosis in Cholangiocarcinoma Cell Line SNU-1079

Choi

Lee

2015

J Korean Med

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This study was performed to investigate the anti-tumor effect of O. japonicus extracts on intrahepatic cholangiocarcinoma cell line SNU-1079. Methods: Cholangiocarcinoma SNU-1079 cells were treated with various concentrations of O. japonicus DW and EtOH extracts (0-300 ㎍/㎖) for 24, 48 or 72 h. Cell viability was evaluated through a PMS/MTS assay, and the apoptosis rate was examined through ELISA assay and flow cytometry analysis. The mRNA expression of apoptosisand cell cycle progression-related genes (Bcl-2, Mcl-1, Bax, Survivin, Cyclin D1, and p21) was evaluated using real-time PCR, and the caspase activity was examined using immunoblot analysis. Results: O. japonicus extracts inhibited cell proliferation and increased apoptosis rate in both ELISA assay and flow cytometry analysis. O. japonicus extracts decreased Bcl-2, Mcl-1, Survivin, and Cyclin D1 mRNA expression and increased Bax mRNA level. O. japonicus extracts also increased Caspase-3 activation. Overall, O. japonicus DW extracts were more effective than EtOH extracts. Conclusions: O. japonicus inhibited cell proliferation and induced apoptosis in SNU-1079 cells via mitochondria-mediated intrinsic pathway, which leads to Caspase-3 activation. The results indicate that O. japonicus is a potential therapeutic herb with anti-tumor effect against intrahepatic cholangiocarcinoma.

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Flavonoids from Orostachys Japonicus A. Berger Induces Caspase-dependent Apoptosis at Least Partly through Activation of p38 MAPK Pathway in U937 Human Leukemic Cells

Cited by 15 publications

References 20 publications

Inhibition of X‑linked inhibitor of apoptosis protein enhances anti‑tumor potency of pure total flavonoids on the growth of leukemic cells

Inhibition of X‑linked inhibitor of apoptosis protein enhances anti‑tumor potency of pure total flavonoids on the growth of leukemic cells

Leukemia therapy by flavonoids: Future and involved mechanisms

Orostachys japonicus DW and EtOH Extracts Induce Apoptosis in Cholangiocarcinoma Cell Line SNU-1079

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