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

Shahriyar, Sk Abrar; Woo, Seon Min; Seo, Seung Un; Min, Kyoung‐jin; Kwon, Taeg Kyu

doi:10.3390/ijms19103280

Cited by 23 publications

(20 citation statements)

References 39 publications

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“…Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) functions as a selective apoptosis-inducing ligand in cancer cells with normal cells remaining unaffected. CEP enhances TRAIL-mediated apoptosis through a down-regulation of survivin expression, not by direct inhibition of survivin mRNA expression but via a downregulation of a deubiquitin protein that modulates survivin expression in renal carcinoma cells (Shahriyar et al, 2018).…”

Section: Anti-cancer Activity Of Cep In Drug Combinationsmentioning

confidence: 97%

Cepharanthine: An update of its mode of action, pharmacological properties and medical applications

2019

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A B S T R A C TBackground: Cepharanthine (CEP) is a drug used in Japan since the 1950s to treat a number of acute and chronic diseases, including treatment of leukopenia, snake bites, xerostomia and alopecia. It is the only approved drug for Human use in the large class of bisbenzylisoquinoline alkaloids. This natural product, mainly isolated from the plant Stephania cephalantha Hayata, exhibits multiple pharmacological properties including anti-oxidative, anti-inflammatory, immuno-regulatory, anti-cancer, anti-viral and anti-parasitic properties. Purpose: The mechanism of action of CEP is multifactorial. The drug exerts membrane effects (modulation of efflux pumps, membrane rigidification) as well as different intracellular and nuclear effects. CEP interferes with several metabolic axes, primarily with the AMP-activated protein kinase (AMPK) and NFκB signaling pathways. In particular, the anti-inflammatory effects of CEP rely on AMPK activation and NFκB inhibition. Conclusion: In this review, the historical discovery and development of CEP are retraced, and the key mediators involved in its mode of action are presented. The past, present, and future of CEP are recapitulated. This review also suggests new opportunities to extend the clinical applications of this well-tolerated old Japanese drug.

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Section: Anti-cancer Activity Of Cep In Drug Combinationsmentioning

confidence: 97%

Cepharanthine: An update of its mode of action, pharmacological properties and medical applications

2019

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“…Cepharanthine dose-dependently downregulated STAMBPL1 and increased USP53 expression. Ectopic expression of STAMBPL1 significantly inhibited cepharanthine-induced reduction in the levels of survivin [43]. Overall, these findings clearly suggest that cepharanthine enhances TRAIL-induced apoptosis by promoting the degradation of survivin through STAMBPL1 downregulation in renal carcinoma cells (Figure 3).…”

Section: Natural-product-mediated Restoration Of Trail-mediated Apmentioning

confidence: 86%

“…Cepharanthine, a biscoclaurine alkaloid isolated from Stephania cepharantha , has been shown to be effective against renal carcinoma cells [43]. Cepharanthine time-dependently induced the downregulation of survivin protein levels.…”

Section: Natural-product-mediated Restoration Of Trail-mediated Apmentioning

confidence: 99%

Natural Product Mediated Regulation of Death Receptors and Intracellular Machinery: Fresh from the Pipeline about TRAIL-Mediated Signaling and Natural TRAIL Sensitizers

Shahwar

Iqbal

Nisa³

et al. 2019

IJMS

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Rapidly developing resistance against different therapeutics is a major stumbling block in the standardization of therapy. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated signaling has emerged as one of the most highly and extensively studied signal transduction cascade that induces apoptosis in cancer cells. Rapidly emerging cutting-edge research has helped us to develop a better understanding of the signaling machinery involved in inducing apoptotic cell death. However, excitingly, cancer cells develop resistance against TRAIL-induced apoptosis through different modes. Loss of cell surface expression of TRAIL receptors and imbalance of stoichiometric ratios of pro- and anti-apoptotic proteins play instrumental roles in rewiring the machinery of cancer cells to develop resistance against TRAIL-based therapeutics. Natural products have shown excellent potential to restore apoptosis in TRAIL-resistant cancer cell lines and in mice xenografted with TRAIL-resistant cancer cells. Significantly refined information has previously been added and continues to enrich the existing pool of knowledge related to the natural-product-mediated upregulation of death receptors, rebalancing of pro- and anti-apoptotic proteins in different cancers. In this mini review, we will set spotlight on the most recently published high-impact research related to underlying mechanisms of TRAIL resistance and how these deregulations can be targeted by natural products to restore TRAIL-mediated apoptosis in different cancers.

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“…In addition, STAMBPL1 stabilizes the human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein [33]. Recently, we reported the depletion of STAMBPL1 increases apoptotic cell death through accumulation of intracellular ROS and lysosome-dependent XIAP degradation in prostate cancer cells [34], and we also reported that levels of STAMBPL1 is correlated with the expression of survivin in cepharanthine treated renal cancer cells [35]. However, the functions of STAMBPL1 and target proteins have not yet been understood.…”

Section: Introductionmentioning

confidence: 85%

“…However, honokiol had no effect on expression of USP8 in renal carcinoma Caki cells ( Figure 5B). In case of survivin, USP9X and STAMBPL1 modulate survivin expression by long noncoding RNA (lncRNA) LNC473 and cepharanthine, respectively [35,61]. LNC473 directly bind survivin and USP9X, and USP9X inhibits ubiquitination of survivin [61].…”

Section: Discussionmentioning

confidence: 99%

Honokiol Enhances TRAIL-Mediated Apoptosis through STAMBPL1-Induced Survivin and c-FLIP Degradation

et al. 2019

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Honokiol is a natural biphenolic compound extracted from traditional Chinese medicine Magnolia species, which have been known to display various biological effects including anti-cancer, anti-proliferative, anti-angiogenic, and anti-metastatic activities in cancer cells. Here, we found that honokiol sensitizes cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through downregulation of anti-apoptotic proteins survivin and c-FLIP. Ectopic expression of survivin and c-FLIP markedly abolished honokiol and TRAIL-induced apoptosis. Mechanistically, honokiol induced protein degradation of c-FLIP and survivin through STAMBPL1, a deubiquitinase. STAMBPL1 interacted with survivin and c-FLIP, resulted in reduction of ubiquitination. Knockdown of STAMBPL1 reduced survivin and c-FLIP protein levels, while overexpression of STAMBPL1 inhibited honokinol-induced survivin and c-FLIP degradation. Our findings provided that honokiol could overcome TRAIL resistance through survivin and c-FLIP degradation induced by inhibition of STAMBPL1 expression.

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

Cited by 23 publications

References 39 publications

Cepharanthine: An update of its mode of action, pharmacological properties and medical applications

Cepharanthine: An update of its mode of action, pharmacological properties and medical applications

Natural Product Mediated Regulation of Death Receptors and Intracellular Machinery: Fresh from the Pipeline about TRAIL-Mediated Signaling and Natural TRAIL Sensitizers

Honokiol Enhances TRAIL-Mediated Apoptosis through STAMBPL1-Induced Survivin and c-FLIP Degradation

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