Fisetin Induces Apoptosis of HSC3 Human Oral Cancer Cells Through Endoplasmic Reticulum Stress and Dysfunction of Mitochondria-mediated Signaling Pathways

Shih, Yu‐Lueng; Hung, Fang Ming; Lee, Ching Hsiao; Yeh, Ming‐Yang; Lee, Mei Hui; Lu, Hsu Feng; Chen, Yung Liang; Liu, Jia You; Chung, Jing Gung

doi:10.21873/invivo.11176

Cited by 26 publications

(25 citation statements)

References 57 publications

(62 reference statements)

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“…Cleaved caspase-3 and cleaved caspase-8 expression have been shown to relate with the mitochondria-dependent apoptotic pathway (Zhang et al, 2013 ; Shih et al, 2017 ). In the present study, the activation of caspase-3 and caspase-8 induced by MPP + could be prevented by the pretreatment of Als.…”

Section: Discussionmentioning

confidence: 99%

GSK-3β Inhibitor Alsterpaullone Attenuates MPP+-Induced Cell Damage in a c-Myc-Dependent Manner in SH-SY5Y Cells

Wang

et al. 2018

Front. Cell. Neurosci.

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Mitochondrial dysfunction plays significant roles in the pathogenesis of Parkinson’s Disease (PD). The inactivation of c-Myc, a down-stream gene of Wnt/β-catenin signaling, may contribute to the mitochondria dysfunction. Inhibition of glycogen synthase kinase 3β (GSK-3β) with Alsterpaullone (Als) can activate the down-stream events of Wnt signaling. Here, we investigated the protective roles of Als against MPP+-induced cell apoptosis in SH-SY5Y cells. The data showed that Als effectively rescued c-Myc from the MPP+-induced decline via Wnt signaling. Furthermore, Als protected SH-SY5Y cells from the MPP+-induced mitochondrial fission and cell apoptosis. However, the protective roles of Als were lost under β-catenin-deficient conditions. These findings indicate that Als, a GSK-3β inhibitor, attenuated the MPP+-induced mitochondria-dependent apoptotic via up-regulation of the Wnt signaling.

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Section: Discussionmentioning

confidence: 99%

GSK-3β Inhibitor Alsterpaullone Attenuates MPP+-Induced Cell Damage in a c-Myc-Dependent Manner in SH-SY5Y Cells

Wang

et al. 2018

Front. Cell. Neurosci.

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“…Fisetin is the dietary flavonoid and exhibits antioxidant, anti-inflammatory, anti-cancer and neuroprotective activities 37. Recent studies demonstrated that fisetin induces apoptotic cell death through the endoplasmic reticulum stress in human melanoma 38 and mitochondria-dependent apoptotic pathway human oral cancer cells 39. Apoptosis is a morphologically, chemically, and pathophysiologically distinct from necrosis, and the development of cancer treatment can be promoted through understanding the mechanism of apoptosis 40.…”

Section: Discussionmentioning

confidence: 99%

Crosstalk between Fisetin-induced Apoptosis and Autophagy in Human Oral Squamous Cell Carcinoma

et al. 2019

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Fisetin (3,3-,4-,7-tetrahydroxyflavone), a naturally occurring flavonoid, has antioxidant, anti-inflammatory, and anticancer effects. Oral squamous cell carcinoma (OSCC) has a 5-year survival rate lower than that of most other carcinomas, and can create functional and aesthetic problems for the patient. New therapies for OSCC are necessary, and treatment using plant-derived natural substances has recently become a trend. It has been suggested that autophagy may play an important role in cancer therapy. Several studies demonstrated that autophagy inhibition enhances apoptotic cell death. Therefore, autophagy inhibition might be a promising therapeutic method against OSCC. Our results showed that fisetin induced apoptotic cell death in human tongue squamous cell line Ca9-22 could be enhanced by inhibition of autophagy. Thus, autophagy process in fisetin treated OSCC might presumed to play a role of pro-survival. The combination of fisetin and an effective autophagy inhibitor could be a potentially adjuvant and useful treatment for oral cancer.

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“…The in vitro activity of fisetin in the mitochondrial apoptotic pathway has been acknowledged to be effective in the treatment of oral carcinomas. Fisetin enhanced the expression of pro-apoptotic proteins Bak and Bax but reduced anti-apoptotic protein expression (Bcl-2 and Bcl-x), while it also led to activation of caspase-3, caspase-8, caspase-9, and augmented sustained release of cytochrome c and apoptosis-inducing factor expression in HSC3 [51] and SCC-4 oral carcinoma cells [52]. Further, Khan et al found fisetin (10-60 µM) treatment resulted in activation of apoptosis, poly (ADP-ribose) polymerase (PARP) cleavage, modulation of Bcl-2 family protein expression (Bak, Bad, Bid, Bcl-xL), inhibition of the phoshoinositide 3-kinase (PI3K)/Akt signaling pathway, and activation of caspase 3, caspase-9, and-8 enzyme activity in LNCaP prostate cancer cell lines [53].…”

Section: Regulation Of Cancer-related Processesmentioning

confidence: 99%

Fisetin and Quercetin: Promising Flavonoids with Chemopreventive Potential

et al. 2019

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Despite advancements in healthcare facilities for diagnosis and treatment, cancer remains the leading cause of death worldwide. As prevention is always better than cure, efficient strategies are needed in order to deal with the menace of cancer. The use of phytochemicals as adjuvant chemotherapeutic agents in heterogeneous human carcinomas like breast, colon, lung, ovary, and prostate cancers has shown an upward trend during the last decade or so. Flavonoids are well-known products of plant derivatives that are reportedly documented to be therapeutically active phytochemicals against many diseases encompassing malignancies, inflammatory disorders (cardiovascular disease, neurodegenerative disorder), and oxidative stress. The current review focuses on two key flavonols, fisetin and quercetin, known for their potential pharmacological relevance. Also, efforts have been made to bring together most of the concrete studies pertaining to the bioactive potential of fisetin and quercetin, especially in the modulation of a range of cancer signaling pathways. Further emphasis has also been made to highlight the molecular action of quercetin and fisetin so that one could explore cancer initiation pathways and progression, which could be helpful in designing effective treatment strategies.

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Fisetin Induces Apoptosis of HSC3 Human Oral Cancer Cells Through Endoplasmic Reticulum Stress and Dysfunction of Mitochondria-mediated Signaling Pathways

Cited by 26 publications

References 57 publications

GSK-3β Inhibitor Alsterpaullone Attenuates MPP+-Induced Cell Damage in a c-Myc-Dependent Manner in SH-SY5Y Cells

GSK-3β Inhibitor Alsterpaullone Attenuates MPP+-Induced Cell Damage in a c-Myc-Dependent Manner in SH-SY5Y Cells

Crosstalk between Fisetin-induced Apoptosis and Autophagy in Human Oral Squamous Cell Carcinoma

Fisetin and Quercetin: Promising Flavonoids with Chemopreventive Potential

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