Delicaflavone induces autophagic cell death in lung cancer via Akt/mTOR/p70S6K signaling pathway

Sui, Yuxia; Yao, Hong; Li, Shaoguang; Jin, Long; Shi, Peiying; Li, Zhijun; Wang, Gang; Lin, Shilan; Wu, Youjia; Li, Yuxiang; Huang, Liying; Liu, Qicai; Lin, Xinhua

doi:10.1007/s00109-016-1487-z

Cited by 49 publications

(43 citation statements)

References 41 publications

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“…Autophagy is known to be a self-degradative process that is important for balancing sources of energy at critical times during development, and in response to nutrient stress ( 32 ). Studies have demonstrated that autophagy is involved in a number of general processes, including proliferation, development, apoptosis and cell death ( 33 , 34 ). LC3BII, Beclin1 and P62 are closely associated with the formation of autophagosomes, serving as markers of autophagy ( 35 ).…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone-induced production of reactive oxygen species promotes apoptosis via endoplasmic reticulum stress and autophagy in MC3T3-E1 cells

Liu

Zhao

et al. 2018

Int J Mol Med

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Apoptosis of osteoblasts, triggered by prolonged or excessive use of glucocorticoids (GCs), has been identified as a dominant contributor to the development of osteoporosis and osteonecrosis. However, the molecular mechanisms underlying GC-induced apoptosis are multifaceted and remain to be fully elucidated. The present study aimed to explore the correlation between dexamethasone (DEX)-induced reactive oxygen species (ROS), autophagy and apoptosis in MC3T3-E1 osteoblast-like cells. Cell viability was assessed using a Cell Counting Kit-8 assay, and flow cytometry was performed to assess cellular apoptosis, cell cycle and ROS production. Immunofluorescence and western blot analysis were respectively used to detect autophagic vacuoles and the expression of proteins, including cyclin D kinase (CDK)2, poly[ADP ribose] polymerase, caspase-3, activating transcription factor (ATF)4, CCAAT/enhancer-binding protein homologous protein (CHOP), Beclin1, microtubule-associated proteins 1A/1B light chain (LC)3B and P62. It was revealed that DEX not only reduced cell viability, but also promoted apoptosis via the activation of endoplasmic reticulum (ER) stress. In addition, DEX induced cell cycle arrest at G0/G1 phase via inhibition of the expression of CDK2, and the production of ROS was activated. Of note, the DEX-mediated changes in viability and apoptosis were attenuated in MC3T3-E1 cells after treatment with 3-methyladenine, which is an autophagy inhibitor. Treatment with the antioxidant N-acetylcysteine abolished the effect of DEX on the proliferation, apoptosis, ER stress and autophagy of MC3T3-E1 cells. In conclusion, the present results indicated that DEX promoted the production of ROS, which enhanced apoptosis through activation of autophagy and ER stress in MC3T3-E1 cells.

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Section: Discussionmentioning

confidence: 99%

Dexamethasone-induced production of reactive oxygen species promotes apoptosis via endoplasmic reticulum stress and autophagy in MC3T3-E1 cells

Liu

Zhao

et al. 2018

Int J Mol Med

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“…The in vivo anticancer effect of the total biflavonoids extract was evaluated according to previous method with slight modification [ 10 , 11 ]. Described briefly, the mouse xenograft model was established by injection of 2 × 10 6 LLC cells s.c. into the right armpit of six to eight-week old C57BL/6 male mice (18–22 g, obtained from the National Rodent Laboratory Animal Resource, Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

“…A few components have been isolated from this plant genus, including flavonoids, lignans, polysaccharides, and so on [ 2 ], some of which have been reported to possess anti-diabetic, anti-inflammation, anti-oxidative, and anti-cancer activities [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. Modern pharmacological studies showed that the ethanol extract of S. doederleinii could induce human nasopharyngeal carcinoma cell (CNE) apoptosis [ 5 ] and because of abundant biflavonoids, the ethyl acetate extract had more powerful anti-cancer activities than the ethanol extract for S. doederleinii [ 6 , 7 , 8 , 9 , 10 , 11 ]. Our recent studies demonstrated that the biflavonoids in S. doederleinii were concentrated mostly in the ethyl acetate extract, and the total biflavonoids could reduce the expression of antigen Ki67, decrease tumor microvessel density (MVD), and significantly inhibit the tumor growth, and did not show apparent oral acutetoxicity in healthy mice [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Analysis of the Total Biflavonoids Extract from Selaginella doederleinii by HPLC-QTOF-MS and Its In Vitro and In Vivo Anticancer Effects

et al. 2017

Self Cite

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Selaginella doederleinii Hieron has been traditionally used as a folk antitumor herbal medicine in China. In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. Four types of biflavonoids from S. doederleinii, including IC3′–IIC8′′, IC3′–IIC6′′, IC3′–IIC3′′′, and C–O linked biflavonoids were examined originally using QTOF MS/MS. The fragmentation behavior of IC3′–IIC3′′′ linked biflavonoids was reported for the first time. A total of twenty biflavonoids were identified or tentatively characterized and eight biflavonoids were found from S. doederleinii for the first time. Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. The results of this work could provide useful knowledge for the identification of biflavonoids in herbal samples and further insights into the chemopreventive function of this plant.

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“…Recent studies on various substances have reported that autophagy plays a paradoxical role in anti-tumor therapy. Induction of autophagic cell death by small molecules contributes to the enhancement of anti-tumor activity of chemotherapy or radiation therapy, whereas autophagy-dependent anti-apoptotic responses induced by chemotherapy have negative impacts on anti-tumor treatment through inhibition of the mTOR pathway 17,18 . To our best knowledge, no association between anti-tumor effects of PAM and autophagy has been reported.…”

mentioning

confidence: 99%

Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway

Yoshikawa

Liu

Nakamura

et al. 2020

Sci Rep

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the biological function of non-thermal atmospheric pressure plasma has been widely accepted in several types of cancer. We previously developed plasma-activated medium (pAM) for clinical use, and demonstrated that PAM exhibits a metastasis-inhibitory effect on ovarian cancer through reduced MMP-9 secretion. However, the anti-tumor effects of PAM on endometrial cancer remain unknown. In this study, we investigated the inhibitory effect of PAM on endometrial cancer cell viability in vitro.Our results demonstrated that AMEC and HEC50 cell viabilities were reduced by PAM at a certain PAM ratio, and PAM treatment effectively increased autophagic cell death in a concentration dependent manner. in addition, we evaluated the molecular mechanism of pAM activity and found that the mtoR pathway was inactivated by pAM. Moreover, our results demonstrated that the autophagy inhibitor MHY1485 partially inhibited the autophagic cell death induced by PAM treatment. These findings indicate that pAM decreases the viability of endometrial cancer cells along with alteration of the mtoR pathway, which is critical for cancer cell viability. collectively, our data suggest that pAM inhibits cell viability while inducing autophagic cell death in endometrial cancer cells, representing a potential novel treatment for endometrial cancer.Endometrial cancer is the most common gynecologic malignancy in Japan, with an estimated 13,600 new cases diagnosed in 2015 1 . The incidence of new cases is believed to have increased over the last few decades due to increased levels of obesity, hypertension, and diabetes mellitus, particularly in South Africa and several Asian countries including Japan 1,2 . Although the majority of endometrial cancer patients are diagnosed in the early stage and outcomes are generally favorable because of the typical symptom of irregular vaginal bleeding in women of menopausal age, the prognoses of patients in advanced stages not amenable to localized therapies remain poor 1 . Indeed, a frequent pattern of progression and recurrence is peritoneal metastasis, which is often resistant to systemic chemotherapy 3 . In addition, cytotoxic agents for endometrial cancer are relatively limited compared with other gynecologic malignancies. Thus, there is an increasing demand for novel approaches to peritoneal dissemination.For the past decade, nonequilibrium atmospheric pressure plasma (NEAPP) has been studied for its clinical applications such as sterilization, wound healing, and cancer therapy 4-6 . NEAPP represents a partially ionized gas with energy mainly accumulated as free electrons 7 . Recent studies have revealed that in addition to the direct irradiation of NEAPP to bacteria or tissues, indirect plasma treatment with plasma-activated medium (PAM) and plasma-activated lactate (PAL), which are activated by NEAPP, exhibit anti-tumor activity in several types of cancer, including ovarian, pancreatic, colorectal and gastric cancers 4,8-13 . The molecular mechanism of the anti-tumor effects triggered by PAM have been investigat...

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Delicaflavone induces autophagic cell death in lung cancer via Akt/mTOR/p70S6K signaling pathway

Cited by 49 publications

References 41 publications

Dexamethasone-induced production of reactive oxygen species promotes apoptosis via endoplasmic reticulum stress and autophagy in MC3T3-E1 cells

Dexamethasone-induced production of reactive oxygen species promotes apoptosis via endoplasmic reticulum stress and autophagy in MC3T3-E1 cells

Analysis of the Total Biflavonoids Extract from Selaginella doederleinii by HPLC-QTOF-MS and Its In Vitro and In Vivo Anticancer Effects

Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway

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