Dihydroartemisinin induces autophagy by suppressing NF-κB activation

Hu, Wei; Chen, Sang-Sang; Zhang, Jiali; Lou, Xiang Yang; Zhou, Huijun

doi:10.1016/j.canlet.2013.09.035

Cited by 84 publications

(66 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, one recent report showed that ART induces autophagy via up-regulation of Beclin 1 expression (16). Moreover, our findings are consistent with three other reports suggesting that DHA was able to induce autophagy in cancer cells (57)(58)(59). DHA is a derivative of artemisinin, with a mechanistic action similar to that of ART (50,60).…”

Section: Discussionsupporting

confidence: 82%

Artesunate Induces Cell Death in Human Cancer Cells via Enhancing Lysosomal Function and Lysosomal Degradation of Ferritin

Yang

Tan

et al. 2014

Journal of Biological Chemistry

135

110

View full text Add to dashboard Cite

Background: Artesunate is capable of inducing cell death in cancer cells. Results: Artesunate accumulates in lysosomes and promotes lysosomal function and ferritin degradation, leading to mitochondrial reactive oxygen species production and eventually cell death. Conclusion: Intracellular iron and ferritin degradation is essential for artesunate-induced lysosomal activation and cell death. Significance: This work reveals a novel mechanism underlying artesunate-induced cell death.

show abstract

Section: Discussionsupporting

confidence: 82%

Artesunate Induces Cell Death in Human Cancer Cells via Enhancing Lysosomal Function and Lysosomal Degradation of Ferritin

Yang

Tan

et al. 2014

Journal of Biological Chemistry

135

110

View full text Add to dashboard Cite

show abstract

“…26 In this study we found that p8-ATF4-CHOP axis is closely related to DHA-induced autophagy. We determined the effect of DHA on formation of acidic vesicular organelles (AVOs) by acridine orange (AO) staining and MDC staining, to visualize autophagosome formation in the cells.…”

Section: P8-atf4-chop Axis Is Involved In Dihydroartemisinin -Inducedmentioning

confidence: 53%

“…22 Interestingly, DHA induced-ER stress has been observed in several tumor cells, 23,24 and our previous studies have demonstrated that DHA both induce apoptosis and autophagy in various cancer cells. 25,26 The Complex relationships among ER stress, autophagy and apoptosis remain unclear, but it's perhaps noteworthy that we found p8 is involved in all of these 3 biological functions induced by DHA.…”

Section: Introductionmentioning

confidence: 89%

p8 attenuates the apoptosis induced by dihydroartemisinin in cancer cells through promoting autophagy

Chen

Zeng

et al. 2015

Cancer Biology & Therapy

Self Cite

View full text Add to dashboard Cite

Dihydroartemisinin (DHA) exhibits anticancer activities in a variety of cancer cells, but DHA alone are not effective enough for cancer therapy. In this study we found the stress-regulated protein p8 was obviously increased after DHA treatment in several cancer cells, which further to induce autophagy by the upregulation of endoplasmic reticulum stress-related protein ATF4 and CHOP. Furthermore, when we silenced p8 by siRNA in cancer cells, the apoptosis induced by DHA were notably increased, whereas the overexpression of p8 in cancer cells leaded to the resistance to DHA-induced apoptosis. Moreover, we found the inhibition of autophagy with chloroquine (CQ) can enhance the anticancer effect of DHA both in vitro and in vivo. In conclusion, we found that p8-mediated autophagy attenuates DHA-induced apoptosis in cancer cells, which provides evidence to support the use p8 as a cancer therapeutic target, and suggests that the combination treatment with DHA and autophagy inhibitor might be an effective cancer therapeutic strategy.

show abstract

“…A1; Zeiss, Germany) using a 490-nm band-pass excitation filters and a 515-nm long-pass barrier filter. Based on the acidity, the lysosomes appeared as orange fluorescent cytoplasmic vesicles (18). sequence was CCuCGuuuGACAuCCACuAdtdt (19).…”

Section: Antibodies and Reagentsmentioning

confidence: 99%

Honokiol exhibits enhanced antitumor effects with chloroquine by inducing cell death and inhibiting autophagy in human non-small cell lung cancer cells

Liu

Shang

et al. 2015

Oncology Reports

View full text Add to dashboard Cite

Abstract. Honokiol (HNK), a potential antitumor compound, has been widely studied in recent years. It induces apoptosis and affects autophagy in cancer cells, yet the mechanism of its antitumor efficacy remains obscure. Chloroquine (CQ), an autophagy inhibitor, is often applied to sensitize antitumor drugs in clinical trials. Here, we investigated the antitumor effect of HNK or CQ alone or in combination in non-small cell lung cancer (NSCLC) cells. Using an experimental approach, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) or sulforhodamine B (SRB) was used to determine the cytotoxicity of the agents. The expression levels of proteins were detected by western blotting. Apoptosis was examined via Annexin V-FITC and PI staining. H460 cell xenografts in nude mice were used to study the effects of HNK and/or CQ in vivo. Transfection with siRNA was applied to knock down cathepsin D. The results demonstrated the enhanced effects of HNK combined with CQ on the inhibition of proliferation, induction of apoptosis in vitro and the reduction in growth in vivo. It was confirmed that HNK and/or CQ triggered apoptosis via a caspase-dependent manner. Furthermore, HNK significantly increased the expression of p62 and LC3-Ⅱ in the A549 and H460 cells and inhibited autophagy and induced apoptosis in a cathepsin D-involved manner. In conclusion, an enhanced antitumor effect was demonstrated following treatment with HNK combined with CQ by inhibiting autophagy and inducing apoptosis via a caspase-dependent and cathepsin D-involved manner. This combination may be a novel and useful antitumor approach for chemotherapy in NSCLC. IntroductionHonokiol (HNK) (Fig. 1A), a biphenolic compound isolated from the leaves, bark, and root of Magnolia officinalis is used in traditional Chinese and Japanese medicine (1). It was reported that HNK effectively reduces the growth of cancer in vitro and in vivo in cell and animal xenograft models (2). It also induces caspase-dependent apoptosis of cancer cells through downregulation of survivin, c-FLIP, Bcl-xL and upregulation of . Recent studies have demonstrated that HNK increases the expression levels of the two hallmarks of autophagy, Beclin-1 and LC3-II, and induces autophagy in glioblastoma multiforme (GBM) DBTRG-05MG cells, yet the role of autophagy in the anti-GBM effects requires further research (6). In addition, HNK was found to induce autophagy in prostate cancer cells (7). However, another study indicated that w007B, a newly synthesized derivative of honokiol, exerted neuroprotective effects through inhibition of autophagy (8). As suggested above, the role of autophagy in the antitumor effects of HNK requires further research and combined treatment of HNK with an autophagy inhibitor or activator may result in enhanced antitumor effects.Autophagy is a conserved, lysosomal-dependent membrane process to maintain cellular homeostasis under metabolic stress. During this process, autophagosomes engulf damaged proteins and defective organelles and then fuse with lysosomes f...

show abstract

Dihydroartemisinin induces autophagy by suppressing NF-κB activation

Cited by 84 publications

References 46 publications

Artesunate Induces Cell Death in Human Cancer Cells via Enhancing Lysosomal Function and Lysosomal Degradation of Ferritin

Artesunate Induces Cell Death in Human Cancer Cells via Enhancing Lysosomal Function and Lysosomal Degradation of Ferritin

p8 attenuates the apoptosis induced by dihydroartemisinin in cancer cells through promoting autophagy

Honokiol exhibits enhanced antitumor effects with chloroquine by inducing cell death and inhibiting autophagy in human non-small cell lung cancer cells

Contact Info

Product

Resources

About