Falcarindiol Stimulates Apoptotic and Autophagic Cell Death to Attenuate Cell Proliferation, Cell Division, and Metastasis through the PI3K/AKT/mTOR/p70S6K Pathway in Human Oral Squamous Cell Carcinomas

2021 ◽  
pp. 1-17
Author(s):  
Kyung-Ran Park ◽  
Hyun Hee Leem ◽  
Yoon-Ju Kwon ◽  
Il Keun Kwon ◽  
Jin Tae Hong ◽  
...  
Keyword(s):  
Cell Death ◽  
Squamous Cell ◽  
Apoptotic Cell ◽  
Squamous Cell Carcinomas ◽  
Apoptotic Cell Death ◽  
Migration And Invasion ◽  
Antitumor Effects ◽  
Oral Squamous Cell Carcinomas ◽  
Beneficial Effects ◽  
Treatment And Prevention

Human oral squamous cell carcinomas (OSCCs) have high cancer mortality and a 5-year survival rate lower than that of most other carcinomas. New therapeutic strategies are required for the treatment and prevention against OSCCs. An approach to cancer therapy using plant-derived natural compounds has been actively in progress as a trend. Falcarindiol (FALC), or its isolated form Ostericum koreanum Kitagawa (O. koreanum), is present in many food and dietary plants, especially in carrots, and this compound has a variety of beneficial effects. However, biological activity of FALC has not been reported in OSCCs yet. This study aimed to demonstrate the antitumor effects of FALC against OSCCs, YD-10B cells. In this study, FALC was selected as a result of screening for compounds isolated from various natural products in YD-10B cells. FALC suppressed cell growth, and FALC-induced apoptotic cell death was mainly accompanied by the dephosphorylation of PI3K, AKT, mTOR, and p70S6K. The apoptotic cell death was also associated with autophagy as evidenced by the expression of Beclin-1, the conversion of LC3-II, and the formation of autophagosome. FALC-induced autophagy was accompanied by MAPKs including ERK1/2 and p38. Furthermore, FALC caused the antimetastatic effects by inhibiting the migration and invasion of YD-10B cells. Taken together, the findings suggest the potential value of FALC as a novel candidate for therapeutic strategy against OSCCs.

scholarly journals Hydrocortisone decreases apoptosis in jejunum of horses subjected to experimental ischemia and reperfusion

2011 ◽  
Vol 31 (6) ◽  
pp. 471-476 ◽  
Author(s):  
Geraldo Eleno S. Alves ◽  
Heloisa M.F. Mendes ◽  
Tiago G.S. Alves ◽  
Rafael R. Faleiros ◽  
Anilton C. Vasconcelos ◽  
...  
Keyword(s):  
Cell Death ◽  
Time Course ◽  
Apoptotic Cell ◽  
Treated Group ◽  
Apoptotic Cell Death ◽  
Apoptotic Cells ◽  
Ischemia And Reperfusion ◽  
Beneficial Effects ◽  
Time Zero ◽  
Venous Ischemia

In order to evaluate the effect of hydrocortisone on apoptosis in the jejunum of horses subjected to ischemia and reperfusion, ten horses were paired and grouped into two groups - treated (n=5) and non treated (n=5). Segments of the jejunum were used as controls (C), or as venous ischemia (VIsc), which were subjected to 2h of ischemia followed by 2 or 12h of reperfusion. C samples were collected at time zero (prior to ischemia) and VIsc samples were collected at 2h of ischemia and at 2 and 12h of reperfusion. TUNEL positive apoptotic cells were counted in 10 microscopical fields in deep mucosa from each horse throughout the time course. After 12h of reperfusion, the number of apoptotic cells in treated group were significantly lower than in untreated animals, indicating that hydrocortisone inhibits apoptosis. These results indicate that hydrocortisone has a beneficial effects favoring the maintenance of jejunal integrity in horses with ischemia and reperfusion injuries by preventing apoptotic cell death.

scholarly journals Melatonin Suppresses Oral Squamous Cell Carcinomas Migration and Invasion through Blocking FGF19/FGFR 4 Signaling Pathway

2021 ◽  
Vol 22 (18) ◽  
pp. 9907
Author(s):  
Leilei Wang ◽  
Yuxiong Su ◽  
Wing Shan Choi
Keyword(s):  
Squamous Cell ◽  
Squamous Cell Carcinomas ◽  
Migration And Invasion ◽  
Promising Alternative ◽  
Oral Squamous Cell Carcinomas ◽  
Invasion And Migration ◽  
Human Tongue ◽  
Underlying Mechanisms ◽  
And Migration ◽  
Fibroblast Growth Factor 19

Oral squamous cell carcinomas (OSCCs) are one of the most prevalent malignancies, with a low five-year survival rate, thus warranting more effective drugs or therapy to improve treatment outcomes. Melatonin has been demonstrated to exhibit oncostatic effects. In this study, we explored the anti-cancer effects of melatonin on OSCCs and the underlying mechanisms. A human tongue squamous cell carcinoma cell line (SCC-15) was treated with 2 mM melatonin, followed by transwell migration and invasion assays. Relative expression levels of Fibroblast Growth Factor 19 (FGF19) was identified by Cytokine Array and further verified by qPCR and Western blot. Overexpression and downregulation of FGF19 were obtained by adding exogenous hFGF19 and FGF19 shRNA lentivirus, respectively. Invasion and migration abilities of SCC-15 cells were suppressed by melatonin, in parallel with the decreased FGF19/FGFR4 expression level. Exogenous hFGF19 eliminated the inhibitory effects of melatonin on SCC-15 cells invasion and migration, while FGF19 knocking-down showed similar inhibitory activities with melatonin. This study proves that melatonin suppresses SCC-15 cells invasion and migration through blocking the FGF19/FGFR4 pathway, which enriches our knowledge on the anticancer effects of melatonin. Blocking the FGF19/FGFR4 pathway by melatonin could be a promising alternative for OSCCs prevention and management, which would facilitate further development of novel strategies to combat OSCCs.

scholarly journals NRF2 Plays a Critical Role in Both Self and EGCG Protection against Diabetic Testicular Damage

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Chenyu Pan ◽  
Shengzhu Zhou ◽  
Junduo Wu ◽  
Lingyun Liu ◽  
Yanyan Song ◽  
...  
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Critical Role ◽  
Epigallocatechin Gallate ◽  
Apoptotic Cell Death ◽  
Related Factor ◽  
Diabetic Mice ◽  
Testicular Damage ◽  
Beneficial Effects ◽  
Testicular Weight

Activation of nuclear factor erythroid 2-related factor 2 (NRF2) has been found to ameliorate diabetic testicular damage (DTD) in rodents. However, it was unclear whether NRF2 is required for these approaches in DTD. Epigallocatechin gallate (EGCG) is a potent activator of NRF2 and has shown beneficial effects on multiple diabetic complications. However, the effect of EGCG has not been studied in DTD. The present study aims to explore the role of NRF2 in both self and EGCG protection against DTD. Therefore, streptozotocin-induced diabetic C57BL/6 wild type (WT) and Nrf2 knockout (KO) mice were treated in the presence or absence of EGCG, for 24 weeks. The Nrf2 KO mice exhibited more significant diabetes-induced loss in testicular weight and spermatozoa count, and increase in testicular apoptotic cell death, as compared with the WT mice. EGCG activated NRF2 expression and function, preserved testicular weight and spermatozoa count, and attenuated testicular apoptotic cell death, endoplasmic reticulum stress, inflammation, and oxidative damage in the WT diabetic mice, but not the Nrf2 KO diabetic mice. The present study demonstrated for the first time that NRF2 plays a critical role in both self and EGCG protection against DTD.

scholarly journals XIAP inhibitor embelin induces autophagic and apoptotic cell death in human oral squamous cell carcinoma cells

2017 ◽  
Vol 32 (11) ◽  
pp. 2371-2378 ◽  
Author(s):  
You-Jin Lee ◽  
Bong-Soo Park ◽  
Hae-Ryoun Park ◽  
Su-Bin Yu ◽  
Hae-Mi Kang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Carcinoma Cells

Demethylzeylasteral Exerts Antitumor Effects via Disruptive Autophagic Flux and Apoptotic Cell Death in Human Colorectal Cancer Cells and Increases Cell Chemosensitivity to 5-Fluorouracil

2021 ◽  
Vol 21 ◽  
Author(s):  
Guiyuan Liu ◽  
Dengxiang Lai ◽  
Yi Jiang ◽  
Hongjing Yang ◽  
Hui Zhao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Autophagic Flux ◽  
Human Colorectal Cancer ◽  
Antitumor Effects ◽  
Tripterygium Wilfordii Hook F ◽  
Pharmacologically Active

Background: Demethylzeylasteral (ZST93), a pharmacologically active triterpenoid monomer extracted from Tripterygium wilfordii Hook F (TWHF), has been reported to exert antineoplastic effects in several cancer cell types. However, the anti-tumour effects of ZST93 in human colorectal cancer (CRC) cells are unknown. Objective: The aim of the present study was to evaluate the antitumor effects of ZST93 on cell cycle arrest, disruptive autophagic flux, apoptotic cell death, and enhanced chemosensitivity to 5-FU in humans CRC cells. Methods: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT) assay, colony formation assay, flow cytometry, immunoblotting, immunofluorescence, 5-ethynyl-20-deoxyuridine (EdU) incorporation assay, and autophagy analysis were used to evaluate the effects of ZST93 on cell viability, cell cycle progression, apoptosis and autophagy in two human CRC cell lines. Moreover, ZST93’s combined anti-tumour effects with 5-fluorouracil (5-FU) were evaluated. Results: ZST93 inhibited CRC cell proliferation and growth. It was responsible for blocked cell cycle transition by arresting CRC cells in the G0/G1 phase via down-regulation of CDK4, CDK6, Cyclin D1, and c-MYC. Moreover, ZST93 induced suppressive autophagic flux and caspase-3-dependent cell death, which were further strengthened by the blocking of the autophagy process using chloroquine (CQ). Moreover, ZST93 enhanced CRC cells’ chemosensitivity to 5-FU via modulation of autophagy and apoptosis. Conclusion: ZST93 exerts anti-tumour effects via disruptive autophagic flux and apoptotic cell death in human CRC cells and increases cell chemosensitivity to 5-FU. These results provide insights into the utilisation of ZST93 as an adjuvant or direct autophagy inhibitor and suggest ZST93 as a novel therapeutic strategy for treating CRC.

scholarly journals Methanol Extract of Holarrhena antidysenterica Inhibits the Growth of Human Oral Squamous Cell Carcinoma Cells and Osteoclastogenesis of Bone Marrow Macrophages

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Heein Yoon ◽  
Junhee Park ◽  
Kwang-Kyun Park ◽  
Jin Kim ◽  
N. Champika Bandara ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Methanol Extract ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Holarrhena Antidysenterica

Oral squamous cell carcinoma (OSCC) frequently invades mandibular bone, and outcomes for treatment with surgical resection are typically poor, ultimately resulting in death. Holarrhena antidysenterica L. (Apocynaceae), distributed throughout Sri Lanka and India, has been used as a folk remedy to treat various diseases. Treatment with methanol extract of H. antidysenterica bark (HABE) inhibited cell viability and BrdU incorporation and induced apoptotic cell death in Ca9-22 gingival and HSC-3 tongue SCC cells. Flow cytometric analysis indicated that HABE treatment preferentially induces apoptotic cell death via increasing the sub-G1 peak in Ca9-22 cells and cell cycle arrest at the G1 phase in HSC-3 cells. HABE treatment in the presence of zVAD-fmk, a pan-caspase inhibitor, rescued cell viabilities in both OSCC cell lines. The ratio of Bax to Bcl-2 increased with reductions in the Bcl-2 protein expression, and the activation of caspase 3 and subsequent cleavage of PARP was detected in HABE-treated Ca9-22 and HSC-3 cells. Furthermore, HABE treatment at noncytotoxic concentrations inhibited osteoclast formation in RANKL-stimulated bone marrow macrophages. Taken together, HABE possesses the inhibitory activity on the growth of OSCC cells and antiosteoclastogenic activity. Therefore, HABE may be a promising alternative and complementary agent for preventing and treating OSCC.

scholarly journals Parthenolide promotes apoptotic cell death and inhibits the migration and invasion of SW620 cells

2017 ◽  
Vol 15 (2) ◽  
pp. 174 ◽  
Author(s):  
Yu Chuan Liu ◽  
Se Lim Kim ◽  
Young Ran Park ◽  
Soo-Teik Lee ◽  
Sang Wook Kim
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Migration And Invasion ◽  
Sw620 Cells
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