scholarly journals Cepharanthine Enhances TRAIL-Mediated Apoptosis Through STAMBPL1-Mediated Downregulation of Survivin Expression in Renal Carcinoma Cells

2018 ◽  
Vol 19 (10) ◽  
pp. 3280 ◽  
Author(s):  
Sk Shahriyar ◽  
Seon Woo ◽  
Seung Seo ◽  
Kyoung-jin Min ◽  
Taeg Kwon
Keyword(s):  
Renal Carcinoma ◽  
Apoptotic Cell ◽  
Combined Treatment ◽  
Ectopic Expression ◽  
Survivin Expression ◽  
Carcinoma Cells ◽  
Inhibitory Protein ◽  
Anticancer Properties ◽  
Induced Apoptosis ◽  
Renal Carcinoma Cells

Cepharanthine (CEP) is a natural plant alkaloid, and has anti-inflammatory, antineoplastic, antioxidative and anticancer properties. In this study, we investigated whether CEP could sensitize renal carcinoma Caki cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. CEP alone and TRAIL alone had no effect on apoptosis. However, combined CEP and TRAIL treatment markedly enhanced apoptotic cell death in cancer cells, but not in normal cells. CEP induced downregulation of survivin and cellular-FLICE inhibitory protein (c-FLIP) expression at post-translational levels. Ectopic expression of survivin blocked apoptosis by combined treatment with CEP plus TRAIL, but not in c-FLIP overexpression. Interestingly, CEP induced survivin downregulation through downregulation of deubiquitin protein of STAM-binding protein-like 1 (STAMBPL1). Overexpression of STAMBPL1 markedly recovered CEP-mediated survivin downregulation. Taken together, our study suggests that CEP sensitizes TRAIL-mediated apoptosis through downregulation of survivin expression at the post-translational levels in renal carcinoma cells.

scholarly journals Maritoclax Enhances TRAIL-Induced Apoptosis via CHOP-Mediated Upregulation of DR5 and miR-708-Mediated Downregulation of cFLIP

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 3030 ◽  
Author(s):  
Mi-Yeon Jeon ◽  
Kyoung-jin Min ◽  
Seon Woo ◽  
Seung Seo ◽  
Yung Choi ◽  
...  
Keyword(s):  
Renal Carcinoma ◽  
Combined Treatment ◽  
Ectopic Expression ◽  
Death Receptor ◽  
Death Receptor 5 ◽  
Active Constituent ◽  
Inhibitory Protein ◽  
Homologous Protein ◽  
Induced Apoptosis ◽  
Sensitizing Effect

Maritoclax, an active constituent isolated from marine bacteria, has been known to induce Mcl-1 downregulation through proteasomal degradation. In this study, we investigated the sensitizing effect of maritoclax on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human renal carcinoma cells. We found that combined treatment with maritoclax and TRAIL markedly induced apoptosis in renal carcinoma (Caki, ACHN and A498), lung cancer (A549) and hepatocellular carcinoma (SK-Hep1) cells. The upregulation of death receptor 5 (DR5) and downregulation of cellular FLICE-inhibitory protein (cFLIP) were involved in maritoclax plus TRAIL-induced apoptosis. Maritoclax-induced DR5 upregulation was regulated by induction of C/EBP homologous protein (CHOP) expression. Interestingly, maritoclax induced cFLIP downregulation through the increased expression of miR-708. Ectopic expression of cFLIP prevented combined maritoclax and TRAIL-induced apoptosis. Taken together, maritoclax sensitized TRAIL-induced apoptosis through CHOP-mediated DR5 upregulation and miR-708-mediated cFLIP downregulation.

scholarly journals WP1130 Enhances TRAIL-Induced Apoptosis through USP9X-Dependent miR-708-Mediated Downregulation of c-FLIP

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 344 ◽  
Author(s):  
Seok Kim ◽  
Seon Woo ◽  
Kyoung-jin Min ◽  
Seung Seo ◽  
Tae-Jin Lee ◽  
...  
Keyword(s):  
Renal Carcinoma ◽  
Mesangial Cells ◽  
Combined Treatment ◽  
Ectopic Expression ◽  
Carcinoma Cells ◽  
Human Mesangial Cells ◽  
Dub Inhibitor ◽  
Induced Apoptosis ◽  
Sensitizing Effect ◽  
Human Renal Carcinoma

WP1130, a partially selective deubiquitinases (DUB) inhibitor, inhibits the deubiquitinating activities of USP5, USP9X, USP14, USP37, and UCHL1. In this study, we investigate whether WP1130 exerts sensitizing effect on TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human renal carcinoma cells. Combinations of WP1130 and TRAIL significantly induced apoptosis in renal carcinoma, lung carcinoma and hepatocellular carcinoma cells, but not in normal cells (human mesangial cells (MC) and normal mouse kidney cells (TCMK-1)). The downregulation of c-FLIP protein expression was involved in combined treatment-induced apoptosis. WP1130-induced c-FLIP downregulation was regulated by microRNA (miR)-708 upregulation via inhibition of USP9X. Interestingly, knockdown of USP9X markedly induced c-FLIP downregulation, upregulation of miR-708 expression and sensitivity to TRAIL. Furthermore, ectopic expression of USP9X prevented c-FLIP downregulation and apoptosis upon combined treatment. In sum, WP1130 sensitized TRAIL-induced apoptosis through miR-708-mediated downregulation of c-FLIP by inhibition of USP9X.

Endoplasmic reticulum stress mediates withaferin A-induced apoptosis in human renal carcinoma cells

2011 ◽  
Vol 25 (3) ◽  
pp. 692-698 ◽  
Author(s):  
Min Jung Choi ◽  
Eun Jung Park ◽  
Kyoung Jin Min ◽  
Jong-Wook Park ◽  
Taeg Kyu Kwon
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Renal Carcinoma ◽  
Carcinoma Cells ◽  
Withaferin A ◽  
Induced Apoptosis ◽  
Human Renal Carcinoma ◽  
Renal Carcinoma Cells

scholarly journals PAX2 inactivation enhances cisplatin-induced apoptosis in renal carcinoma cells

2006 ◽  
Vol 69 (7) ◽  
pp. 1139-1145 ◽  
Author(s):  
P.-A. Hueber ◽  
P. Waters ◽  
P. Clarke ◽  
M. Eccles ◽  
P. Goodyer
Keyword(s):  
Renal Carcinoma ◽  
Carcinoma Cells ◽  
Induced Apoptosis ◽  
Renal Carcinoma Cells

scholarly journals Manuka honey enhanced sensitivity of HepG2, hepatocellular carcinoma cells, for Doxorubicin and induced apoptosis through inhibition of Wnt/β-catenin and ERK1/2

2021 ◽  
Vol 54 (1) ◽  
Author(s):  
Heba R. Al Refaey ◽  
Al-Sayeda A. Newairy ◽  
Mayssaa M. Wahby ◽  
Chris Albanese ◽  
Mohamed Elkewedi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Apoptotic Cell ◽  
Combined Treatment ◽  
Inhibitory Effect ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Manuka Honey ◽  
Anticancer Properties ◽  
Hep3b Cells ◽  
Induced Apoptosis

Abstract Background Recently, there is increasing awareness focused on the identification of naturally occurring anticancer agents derived from natural products. Manuka honey (MH) has been recognized for its biological properties as antimicrobial, antioxidant, and anticancer properties. However, its antiproliferative mechanism in hepatocellular carcinoma is not investigated. The current study focused mainly on investigating the molecular mechanism and synergistic effect of anticancer properties of MH on Doxorubicin (DOX)-mediated apoptotic cell death, using two different p53 statuses (HepG2 and Hep3B) and one non-tumorigenic immortalized liver cell line. Results MH treatment showed a proliferative inhibitory effect on tested cells in a dose-dependent manner with IC50 concentration of (6.92 ± 0.005%) and (18.62 ± 0.07%) for HepG2 and Hep3B cells, respectively, and induced dramatic morphological changes of Hep-G2 cells, which considered as characteristics feature of apoptosis induction after 48 h of treatment. Our results showed that MH or combined treatments induced higher cytotoxicity in p53-wild type, HepG2, than in p53-null, Hep3B, cells. Cytotoxicity was not observed in normal liver cells. Furthermore, the synergistic effect of MH and Dox on apoptosis was evidenced by increased annexin-V-positive cells and Sub-G1 cells in both tested cell lines with a significant increase in the percentage of Hep-G2 cells at late apoptosis as confirmed by the flow cytometric analysis. Consistently, the proteolytic activities of caspase-3 and the degradation of poly (ADP-ribose) polymerase were also higher in the combined treatment which in turn accompanied by significant inhibitory effects of pERK1/2, mTOR, S6K, oncogenic β-catenin, and cyclin D1 after 48 h. In contrast, the MH or combined treatment-induced apoptosis was accompanied by significantly upregulated expression of proapoptotic Bax protein and downregulated expression of anti-apoptotic Bcl-2 protein after 48 h. Conclusions Our data showed a synergistic inhibitory effect of MH on DOX-mediated apoptotic cell death in HCC cells. To our knowledge, the present study provides the first report on the anticancer activity of MH and its combined treatment with DOX on HCC cell lines, introducing MH as a promising natural and nontoxic anticancer compound.

scholarly journals Effects of cucurbitacins on cell morphology are associated with sensitization of renal carcinoma cells to TRAIL-induced apoptosis

APOPTOSIS ◽  
2011 ◽  
Vol 17 (1) ◽  
pp. 79-89 ◽  
Author(s):  
Curtis J. Henrich ◽  
Cheryl L. Thomas ◽  
Alan D. Brooks ◽  
Nancy Lynn Booth ◽  
Evan M. Lowery ◽  
...  
Keyword(s):  
Cell Morphology ◽  
Renal Carcinoma ◽  
Carcinoma Cells ◽  
Induced Apoptosis ◽  
Renal Carcinoma Cells

scholarly journals Lucanthone, Autophagy Inhibitor, Enhances the Apoptotic Effects of TRAIL through miR-216a-5p-Mediated DR5 Upregulation and DUB3-Mediated Mcl-1 Downregulation

2021 ◽  
Vol 23 (1) ◽  
pp. 17
Author(s):  
Ji Yun Yoon ◽  
Seon Min Woo ◽  
Seung Un Seo ◽  
So Rae Song ◽  
Seul Gi Lee ◽  
...  
Keyword(s):  
Renal Carcinoma ◽  
Combined Treatment ◽  
Ectopic Expression ◽  
A549 Cells ◽  
Expression Level ◽  
Human Skin Fibroblast ◽  
Normal Human Skin ◽  
Induced Apoptosis ◽  
Apoptotic Effects ◽  
Human Renal Carcinoma

A lucanthone, one of the family of thioxanthenones, has been reported for its inhibitory effects of apurinic endonuclease-1 and autophagy. In this study, we investigated whether lucanthone could enhance tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in various cancer cells. Combined treatment with lucanthone and TRAIL significantly induced apoptosis in human renal carcinoma (Caki and ACHN), prostate carcinoma (PC3), and lung carcinoma (A549) cells. However, combined treatment did not induce apoptosis in normal mouse kidney cells (TCMK-1) and normal human skin fibroblast (HSF). Lucanthone downregulated protein expression of deubiquitinase DUB3, and a decreased expression level of DUB3 markedly led to enhance TRAIL-induced apoptosis. Ectopic expression of DUB3 inhibited combined treatment with lucanthone and TRAIL-induced apoptosis. Moreover, lucanthone increased expression level of DR5 mRNA via downregulation of miR-216a-5p. Transfection of miR-216a-5p mimics suppressed the lucanthone-induced DR5 upregulation. Taken together, these results provide the first evidence that lucanthone enhances TRAIL-induced apoptosis through DR5 upregulation by downregulation of miR-216a-5p and DUB3-dependent Mcl-1 downregulation in human renal carcinoma cells.

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