Luteolin sensitizes human liver cancer cells to TRAIL‑induced apoptosis via autophagy and JNK‑mediated death receptor 5 upregulation

Nazim, Uddin Md.; Park, Sang-Youel

doi:10.3892/ijo.2018.4633

Cited by 29 publications

(26 citation statements)

References 57 publications

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“…For example, Park et al reported that luteolin induced endoplasmic reticulum stress-mediated apoptosis and Beclin 1-independent autophagy in NCI-H460 lung carcinoma cells [135]. Luteolin (20 µM) induced autophagic flux in human liver cancer cells Huh7 by upregulating LC3 II and inhibiting p62 expression, thus sensitizing cells to TRAIL-induced cell death [136]. The same effects of luteolin were obtained by Cao et al in human liver cancer SMMC-7721 cells.…”

Section: Flavonesmentioning

confidence: 62%

Polyphenol-Mediated Autophagy in Cancer: Evidence of In Vitro and In Vivo Studies

Benvenuto

Albonici

Focaccetti

et al. 2020

IJMS

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One of the hallmarks of cellular transformation is the altered mechanism of cell death. There are three main types of cell death, characterized by different morphological and biochemical features, namely apoptosis (type I), autophagic cell death (type II) and necrosis (type III). Autophagy, or self-eating, is a tightly regulated process involved in stress responses, and it is a lysosomal degradation process. The role of autophagy in cancer is controversial and has been associated with both the induction and the inhibition of tumor growth. Autophagy can exert tumor suppression through the degradation of oncogenic proteins, suppression of inflammation, chronic tissue damage and ultimately by preventing mutations and genetic instability. On the other hand, tumor cells activate autophagy for survival in cellular stress conditions. Thus, autophagy modulation could represent a promising therapeutic strategy for cancer. Several studies have shown that polyphenols, natural compounds found in foods and beverages of plant origin, can efficiently modulate autophagy in several types of cancer. In this review, we summarize the current knowledge on the effects of polyphenols on autophagy, highlighting the conceptual benefits or drawbacks and subtle cell-specific effects of polyphenols for envisioning future therapies employing polyphenols as chemoadjuvants.

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Section: Flavonesmentioning

confidence: 62%

Polyphenol-Mediated Autophagy in Cancer: Evidence of In Vitro and In Vivo Studies

Benvenuto

Albonici

Focaccetti

et al. 2020

IJMS

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“…Several studies have reported that the JNK signalling pathway is associated with the expression of DR (Death Receptor) markers and apoptosis [35,36]. To reveal the underlying mechanisms by which V-ATPase de ciency promotes apoptosis, we knocked down or overexpressed V-ATPase in GC-2 cells and analysed the protein expression of total and phosphorylated JNK and c-Jun by western blot.…”

Section: Hypoxia-induced V-atpase De Ciency Promoted Gc-2 Apoptosis Vmentioning

confidence: 99%

V-ATPase Deficiency Aggravates Hypoxia-induced Spermatogenesis Reduction by Promoting Spermatocyte Apoptosis via the JNK/c-Jun Pathway in Mice

Yin

Han

et al. 2021

Preprint

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Spermatocyte apoptosis is the primary cause of poor outcome after hypoxia-triggered spermatogenesis reduction (HSR). The vacuolar H+-ATPase (V-ATPase) has been found to be involved in the regulation of hypoxia-induced GC-2 cells apoptosis. However, the mechanism of V-ATPase regulating spermatocyte apoptosis after HSR hasnot been well elucidated. In this study, HSRmodel was established by hypoxia exposure in vivo in V-ATPase-knockout (V-ATPase-/-) and wild-type (WT) mice to investigate theeffectof V-ATPase deficiency on spermatocyte apoptosis. GC-2, amouse pachytene spermatocyte-derived cell line, was introduced in vitro experiments. The sperm count and spermatogenic apoptosis were recorded after 60 d of hypoxia exposure in HSR model. The apoptosis of GC-2 cells was detected by flow cytometry and TUNEL staining. The expression of JNK/c-Jun was evaluated by RNA-seq or western blot. The expression of DR5 and caspase-8 was evaluated by RT-qPCR and western blot. The expression of V-ATPase was determined by western blot in the presence and absence ofLenti-transcription factor EB (TFEB).C-Jun interference was used for evaluating the role of JNK in regulating the apoptosis of GC-2 cells byTUNEL and flow cytometry. The in vivo results suggested that hypoxia induced spermatogenesis reduction and downregulation of V-ATPase. Moreover, V-ATPase deficiency resulted in moresevere spermatogenesis reduction after hypoxia exposure. The spermatogenesis reduction was associated with exacerbation of spermatocyte apoptosis. Hypoxia down-regulated the transcription of V-ATPase through inhibiting TFEB and its nuclear translocation. The mRNA and protein expressions of V-ATPaseincreased after TFEB overexpression in GC-2 cells. Moreover, V-ATPase deficiency enhanced JNK/c-Jun activation and related DR-apoptotic pathwayin GC-2 cells.However,inhibition of c-Jun attenuated V-ATPase deficiency-induced GC-2 cells apoptosis in vitro and HSR in vivo. In conclusion, JNK/c-Jun was involved in the enhancement of V-ATPase-mediated HSR in V-ATPase -/- mice. V-ATPase deficiency aggravates spermatocyte apoptosis, which may account forthe poor spermatogenesis outcomes of V-ATPase-/- mice. The discoveredfunction of V-ATPase modulating spermatocyte apoptosis indicates its potential therapeutic effect against HSR.

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“…Thus, these results clearly showed that miR-7-1-3p overexpression increased the anti-tumor activities of silibinin (50 µM) and luteolin (20 µM) to inhibit autophagy and induce apoptosis for controlling the growth of different human glioblastomas in vivo. Thus, autophagy can also act as a cell-survival mechanism in glioblastoma cells via Beclin-1 down-regulation [ 35 ].…”

Section: Regulation Of Autophagy By Luteolin In Cancer Cellsmentioning

confidence: 99%

“…Luteolin also regulates autophagy involved in the sensitization of cancer cells to apoptosis [ 35 ]. Luteolin (20 µM) induce sensitization of human liver cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through autophagy by decreasing the level of p62 and up-regulation of JNK-mediated death receptor.…”

Section: Regulation Of Autophagy By Luteolin In Cancer Cellsmentioning

confidence: 99%

Autophagy regulation using luteolin: new insight into its anti-tumor activity

et al. 2020

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Application of novel methods in cancer therapy is important in terms of management and treatment of the life-threatening disorder. It appears that autophagy is a potential target in cancer therapy, as a variety of drugs targeting autophagy have shown great potential in reducing the viability and proliferation of cancer cells. Autophagy is primarily a catabolic process which provides energy during starvation. Besides, this process contributes to the degradation of aged or potentially toxic components and organelles. On the other hand, the source of a variety of naturally occurring anti-tumor drugs are flavonoids which have high anti-tumor activity. Luteolin is a polyphenolic flavone with the great pharmacological effects such as anti-diabetic, hepatoprotective, antioxidant, anti-inflammation, and anti-tumor. At the present review, we demonstrate how luteolin affects on autophagy process to induce anti-tumor activity.

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Luteolin sensitizes human liver cancer cells to TRAIL‑induced apoptosis via autophagy and JNK‑mediated death receptor 5 upregulation

Cited by 29 publications

References 57 publications

Polyphenol-Mediated Autophagy in Cancer: Evidence of In Vitro and In Vivo Studies

Polyphenol-Mediated Autophagy in Cancer: Evidence of In Vitro and In Vivo Studies

V-ATPase Deficiency Aggravates Hypoxia-induced Spermatogenesis Reduction by Promoting Spermatocyte Apoptosis via the JNK/c-Jun Pathway in Mice

Autophagy regulation using luteolin: new insight into its anti-tumor activity

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