Chrysin overcomes TRAIL resistance of cancer cells through Mcl-1 downregulation by inhibiting STAT3 phosphorylation

Lirdprapamongkol, Kriengsak; Sakurai, Hiroaki; Abdelhamed, Sherif; Yokoyama, Satoru; Athikomkulchai, Sirivan; Viriyaroj, Amornrat; Awale, Suresh; Ruchirawat, Somsak; Svasti, Jisnuson; Saiki, Ikuo

doi:10.3892/ijo.2013.1926

Cited by 64 publications

(41 citation statements)

References 42 publications

(36 reference statements)

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“…11,12,20) In addition, chrysin also reported to inhibit cell migration and tube formation ability of HUVECs which induced by several stimulators such as VEGF and IL-6 through suppression of the sIL-6R/gp130/Janus kinase (JAK) 1/STAT3/VEGF signaling pathway. 18,20,21,23) However, the mechanisms of chrysin on lymphatic endothelial cells have not been proved.…”

Section: Discussionmentioning

confidence: 99%

“…9,11,12) In addition, chrysin inhibits angiogenesis by suppression of endothelial cell proliferation and migration in human umbilical vascular endothelial cells (HUVEC). [18][19][20][21] However, the potency of chrysin on lymphangiogenesis is not currently available.…”

Section: Discussionmentioning

confidence: 99%

“…Chrysin (732 mg) was isolated by crystallization from fraction 8 (9.5 g), 2% MeOH-CH 2 Cl 2 eluate, and was identified by comparison of physical and spectroscopic data with authentic standard and literature values. [10][11][12] Chrysin was dissolved in dimethyl sulfoxide (DMSO) for further experiments.…”

Section: Preparation Of Extractsmentioning

confidence: 99%

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Chrysin Inhibits Lymphangiogenesis <i>in Vitro</i>

Prangsaengtong

Athikomkulchai

et al. 2016

Biological & Pharmaceutical Bulletin

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The induction of lymphangiogenesis is an important process to promote cancer growth and cancer metastasis via the lymphatic system. Identifying the compounds that can prevent lymphangiogenesis for cancer therapy is urgently required. Chrysin, 5,7-dihydroxyflavone, a natural flavone extracted from Thai propolis, was used to investigate the effect on the lymphangiogenesis process of TR-LE, rat lymphatic endothelial cells. In this study, maximal nontoxic doses of chrysin on TR-LE cells were selected by performing a proliferation assay. The process of lymphangiogenesis in vitro was determined by cord formation assay, adhesion assay and migration assay. Chrysin at a nontoxic dose (25 μM) significantly inhibited cord formation, cell adhesion and migration of TR-LE cells when compared with the control group. We also found that chrysin significantly induced vascular endothelial growth factor C (VEGF-C) mRNA expression and nitric oxide (NO) production in TR-LE cells which was involved in decreasing the cord formation of TR-LE cells. In conclusion, we report for the first time that chrysin inhibited the process of lymphangiogenesis in an in vitro model. This finding may prove to be a natural compound for anti-lymphangiogenesis that could be developed for use in cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Chrysin Inhibits Lymphangiogenesis <i>in Vitro</i>

Prangsaengtong

Athikomkulchai

et al. 2016

Biological & Pharmaceutical Bulletin

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“…Immunoblot analysis was performed as previously described (30). HeLa cells were seeded and grown overnight in a 6-well plate (1x10 6 /2 ml/well) in culture medium.…”

Section: Methodsmentioning

confidence: 99%

“…Treatment of the HeLa cells by up to 200 ng/ml of TRAIL for 24 h was reported to have little effect on cell death (<20%) (30,31). Therefore, the concentration of TRAIL was fixed at 200 ng/ml for all TRAIL studies.…”

Section: Ethanolic Extract Of T Peruviana Flowers Enhances Trail-indmentioning

confidence: 99%

Ethanolic extract of Thevetia peruviana flowers enhances TNF-α and TRAIL-induced apoptosis of human cervical cancer cells via intrinsic and extrinsic pathways

2017

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Abstract. Tumor necrosis factor-α (TNF-α) and TNF-related apoptosis-inducing ligand (TRAIL) are promising candidates for cancer treatment due to their ability to induce apoptosis through death receptor stimulation. However, their usage may be limited due to the resistance of cancer cells to TNF-α-and TRAIL-induced apoptosis. Currently, there is interest in screening for natural products that can sensitize cancer cells to TNF-α-and TRAIL-induced apoptosis for their use in combination with TNF-α or TRAIL. It was previously reported that the bark extract of Thevetia peruviana showed a reversal effect on TRAIL-resistance in human gastric adenocarcinoma cell lines. In the present study, the effects of the ethanolic extract of T. peruviana flowers on TNF-α-and TRAIL-induced apoptosis of human cervical cancer HeLa cells were investigated in vitro by determining cell viability and apoptosis using a WST-1 cell proliferation assay and immunoblot analysis, respectively. The ethanolic extract of T. peruviana flowers promoted TNF-α and TRAIL-mediated cell death through the activation of the caspase cascade, poly(ADP-ribose) polymerase and BH3-interacting domain death agonist cleavage. Combined treatment using the extract plus TNF-α resulted in downregulation of anti-apoptotic protein, including myeloid cell leukemia sequence-1, B-cell lymphoma-extra large (Bcl-XL), X-linked inhibitor of apoptosis protein and survivin, while the combined treatment with TRAIL downregulated Bcl-XL. Thus, the ethanolic extract of T. peruviana flowers has potential in sensitizing the TNF-α-and TRAIL-induced apoptosis of HeLa cells via the intrinsic and extrinsic pathways. IntroductionChemotherapy is one of the major standard treatments that is beneficial for numerous cancer types due to its efficient induction of tumor cell death by apoptosis. At present, the cancer resistance of chemotherapeutic drugs is a major drawback that leads to the failure of cancer treatments. Chemotherapeutic drugs eliminate tumor cells by the induction of apoptosis via two distinct pathways, which act through the mitochondria (intrinsic signaling pathway) or through death receptors on the cell surface (extrinsic signaling pathway) (1). Induction of apoptosis via the intrinsic signaling pathway is initiated by severe cell stress, including DNA damage, mitotic catastrophe, hypoxia and cell cycle checkpoint defects. The majority of conventional chemotherapeutic drugs trigger DNA damage and induce apoptosis via the intrinsic signaling pathway by the activation of tumor suppressor protein, p53, which leads to the breakdown of mitochondrial membrane and the release of cytochrome c into the cytosol. Cytochrome c binds to the adaptor apoptotic protease activating factor 1, forming an apoptosome. The apoptosome subsequently activates caspase-9 and caspase-3, which results in the cleavage of death substrates (2-4). Defects in intrinsic apoptosis signal transduction, such as the mutation of p53, contributes to the chemotherapeutic drug resistance of cancer (5,6). The extrinsic pa...

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