Induction of sestrin 2 is associated with fisetin-mediated apoptosis in human head and neck cancer cell lines

Won, Dong‐Hoon; Chung, Sungkwon; Shin, Ji‐Ae; Hong, Kyoung‐Ok; Yang, In‐Hyoung; Yun, Jun-Won; Cho, Sung‐Dae

doi:10.3164/jcbn.18-63

Cited by 27 publications

(19 citation statements)

References 30 publications

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“…[17][18][19] It was recently reported to have antiproliferative and apoptotic activity in various cancer cell lines, including human head and neck cancer, osteosarcoma, breast cancer, and renal cancer stem cell, suggesting that it could be used as a novel anti-cancer agent. [20][21][22][23] We previously confirmed that fisetin inhibited malignant proliferation in human OSCC by blocking the Met/Src signaling pathway. 24 However, no crucial downstream molecular targets for the anti-proliferation effect of fisetin in OSCC have yet been identified.…”

Section: Introductionmentioning

confidence: 70%

<p>Fisetin Modulates Human Oral Squamous Cell Carcinoma Proliferation by Blocking PAK4 Signaling Pathways</p>

Li¹,

Jia²,

Dai³

2020

DDDT

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Objective: Human oral squamous cell carcinoma (OSCC) is a major cause of mortality and morbidity worldwide. There is an urgent need to identify bioactive molecules and potential target genes that could inhibit carcinogenesis for OSCC therapy. Fisetin (3,7,3′,4′-tetrahydroxyflavone), a naturally occurring flavonoid, has been previously shown to have anti-proliferative activities in OSCC; however, its molecular mechanism is unknown. Methods: Colony formation, cell viability, Boyden chamber, wound healing, and tumor xenograft assays were used to detect the impact of fisetin on OSCC cells in vitro and in vivo. Western blot analysis was used to examine the corresponding protein expression. Results: Fisetin treatment significantly inhibited proliferation and promoted apoptosis by repressing PAK4 expression. Moreover, fisetin treatment attenuated cell migration by blocking PAK4 signaling pathways. In addition, the tumor xenograft showed anti-tumor growth effects of fisetin exposure in vivo. Conclusion: Fisetin may represent a potential therapeutic strategy for human OSCC by targeting PAK4 signaling pathways.

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Section: Introductionmentioning

confidence: 70%

<p>Fisetin Modulates Human Oral Squamous Cell Carcinoma Proliferation by Blocking PAK4 Signaling Pathways</p>

Li¹,

Jia²,

Dai³

2020

DDDT

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“…On the other hand, Sestrins may block oxidative damage-associated chemotherapy by reducing ROS (Budanov and Karin, 2008;Hagenbuchner et al, 2012). Sestrins were upregulated upon drug treatments in various type of pre-and mature-tumors as cell survival mechanism: head and neck cancers (Won et al, 2019), non-alcoholic steatohepatitis (Huang et al, 2020), HCC (Dai et al, 2018), osteosarcoma (Yen et al, 2018), acute pancreatitis (Norberg et al, 2018), colitis (Ro et al, 2016), bladder cancer (Hua et al, 2018), and prostate cancer (Fu et al, 2018;Shan et al, 2019). The distinctive roles of Sestrins as tumor suppressor or oncogene in the early or late stages of cancers need further investigation (Sanchez-Alvarez et al, 2019).…”

Section: Sestrins In Nutrient Stress-sensing and Metabolic Dysfunctionmentioning

confidence: 99%

SESTRINs: Emerging Dynamic Stress-Sensors in Metabolic and Environmental Health

Fay

Cyuzuzo

et al. 2020

Front. Cell Dev. Biol.

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Proper timely management of various external and internal stresses is critical for metabolic and redox homeostasis in mammals. In particular, dysregulation of mechanistic target of rapamycin complex (mTORC) triggered from metabolic stress and accumulation of reactive oxygen species (ROS) generated from environmental and genotoxic stress are well-known culprits leading to chronic metabolic disease conditions in humans. Sestrins are one of the metabolic and environmental stress-responsive groups of proteins, which solely have the ability to regulate both mTORC activity and ROS levels in cells, tissues and organs. While Sestrins are originally reported as one of several p53 target genes, recent studies have further delineated the roles of this group of stress-sensing proteins in the regulation of insulin sensitivity, glucose and fat metabolism, and redox-function in metabolic disease and aging. In this review, we discuss recent studies that investigated and manipulated Sestrins-mediated stress signaling pathways in metabolic and environmental health. Sestrins as an emerging dynamic group of stress-sensor proteins are drawing a spotlight as a preventive or therapeutic mechanism in both metabolic stress-associated pathologies and aging processes at the same time.

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“…The cell separates itself from the surrounding tissue, its contours become undulated and extensions are created. Such changes in cell morphology were shown in CAL-27, Ca9-22 [ 26 ], and HSC-3 [ 27 , 28 ] cell lines treated with fisetin. In some cases these effects were time-dependent.…”

Section: Anticancer Potential Of Flavonolsmentioning

confidence: 82%

“…Western blot analysis showed an increased PARP cut and an increased cleavage of caspase-3 fragments [ 33 ]. An increased PARP cleavage was also observed in case of HSC3 cells treated with fisetin [ 28 ]. Fisetin in high concentrations induces apoptosis and stimulates activation of cleaved caspase-3 and caspase-9, which leads to an increased PARP cut in Tu212 cells.…”

Section: Anticancer Potential Of Flavonolsmentioning

confidence: 99%

“…The studies showed that fisetin also decreased total viability of tongue squamous cell carcinoma cell line HSC3 depending on the dose and cell exposure time, while IC 50 value equaled 40 µM in case of the gum cancer cells [ 27 ]. Other researcher used the same cell line and showed that IC 50 value was lower more than half and equaled about 20 µM (after 24 h) [ 28 ]. Fisetin also decreases viability of SCC-4 cells depending on the dose and time, with IC 50 equaling to 52.8 µM after 48 h of treatment [ 29 ].…”

Section: Anticancer Potential Of Flavonolsmentioning

confidence: 99%

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Anticancer Potential of Selected Flavonols: Fisetin, Kaempferol, and Quercetin on Head and Neck Cancers

Kubina

Kabała‐Dzik

2021

Nutrients

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Flavonols are ones of the most common phytochemicals found in diets rich in fruit and vegetables. Research suggests that molecular functions of flavonoids may bring a number of health benefits to people, including the following: decrease inflammation, change disease activity, and alleviate resistance to antibiotics as well as chemotherapeutics. Their antiproliferative, antioxidant, anti-inflammatory, and antineoplastic activity has been proved. They may act as antioxidants, while preventing DNA damage by scavenging reactive oxygen radicals, reinforcing DNA repair, disrupting chemical damages by induction of phase II enzymes, and modifying signal transduction pathways. One of such research areas is a potential effect of flavonoids on the risk of developing cancer. The aim of our paper is to present a systematic review of antineoplastic activity of flavonols in general. Special attention was paid to selected flavonols: fisetin, kaempferol, and quercetin in preclinical and in vitro studies. Study results prove antiproliferative and proapoptotic properties of flavonols with regard to head and neck cancer. However, few study papers evaluate specific activities during various processes associated with cancer progression. Moreover, an attempt was made to collect the majority of substantive studies on bioactive potential of the selected flavonols, especially with regard to modulation of a range of signal transduction pathways that participate in cancer development.

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Induction of sestrin 2 is associated with fisetin-mediated apoptosis in human head and neck cancer cell lines

Cited by 27 publications

References 30 publications

<p>Fisetin Modulates Human Oral Squamous Cell Carcinoma Proliferation by Blocking PAK4 Signaling Pathways</p>

<p>Fisetin Modulates Human Oral Squamous Cell Carcinoma Proliferation by Blocking PAK4 Signaling Pathways</p>

SESTRINs: Emerging Dynamic Stress-Sensors in Metabolic and Environmental Health

Anticancer Potential of Selected Flavonols: Fisetin, Kaempferol, and Quercetin on Head and Neck Cancers

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