Paeonol induces cytoprotective autophagy via blocking the Akt/mTOR pathway in ovarian cancer cells

Gao, Likun; Wang, Zhi; Lu, Danhua; Huang, Jinling; Liu, Jin; Li, Hong

doi:10.1038/s41419-019-1849-x

Cited by 69 publications

(48 citation statements)

References 45 publications

(58 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ROS, small and highly reactive molecules, are the normal metabolite products of mitochondria, and ROS overproduction serves as an important mediator in cell death in response to various stimuli [33][34][35] . Accumulating evidence has indicated that excessive ROS generation contributes to cell cycle arrest and mitochondriadependent apoptosis 36,37 .…”

Section: Discussionmentioning

confidence: 99%

Bruceine D induces lung cancer cell apoptosis and autophagy via the ROS/MAPK signaling pathway in vitro and in vivo

et al. 2020

View full text Add to dashboard Cite

Worldwide, lung cancer remains a leading cause of cancer mortality. Bruceine D (BD) has been shown to induce pancreatic cancer cell death via several different mechanisms. In this study, we demonstrated that BD inhibited lung cancer cell proliferation. Apoptosis and autophagy were the most important mechanisms involved in BD-induced lung cancer cell death, and complete autophagic flux was observed in A549 and NCI-H292 cells. In addition, BD significantly improved intracellular reactive oxygen species (ROS) levels. BD-mediated cell apoptosis and autophagy were almost inhibited in cells pretreated with N-acetylcysteine (NAC), an ROS scavenger. Furthermore, MAPK signaling pathway activation contributed to BD-induced cell proliferation inhibition and NAC could eliminate p-ERK and p-JNK upregulation. Finally, an in vivo study indicated that BD inhibited the growth of lung cancer xenografts. Overall, BD is a promising candidate for the treatment of lung cancer owing to its multiple mechanisms and low toxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

Bruceine D induces lung cancer cell apoptosis and autophagy via the ROS/MAPK signaling pathway in vitro and in vivo

et al. 2020

View full text Add to dashboard Cite

show abstract

“…TEM assay was performed as described previously 23 . Briefly, alteronol-treated A375 cells were harvested and fixed in 0.1 M sodium cacodylate buffer containing 2.5% glutaraldehyde at 4°C and post-fixed with 1% osmium tetroxide for 3 h. The sample was dehydrated and embedded in EMbed 812 (Electron Microscopy Sciences).…”

Section: Transmission Electron Microscopy (Tem)mentioning

confidence: 99%

Autophagy inhibition potentiates the anti-EMT effects of alteronol through TGF-β/Smad3 signaling in melanoma cells

et al. 2020

View full text Add to dashboard Cite

Accumulating evidence demonstrated that alteronol, a novel compound that has a similar structure with paclitaxel, exerts anticancer effects against diversified tumors. However, whether alteronol induces autophagy and the relationship between its anticancer effects and autophagy in melanoma remains elusive. In this study, we show that alteronol induces not only anti-proliferation activity and apoptosis but also autophagy in A375 and UACC62 cells. In addition, alteronol inhibits A375 and UACC62 cells invasion and migration by preventing the epithelial-mesenchymal transition (EMT). Blocking autophagy enhances alteronol-induced apoptosis and anti-EMT effects in vitro and in vivo. Mechanistically, we find that alteronol significantly inhibits Akt/mTOR and TGFβ/Smad3 pathways, and co-treatment with autophagy inhibitor 3-MA further potentiate these effects. Our results suggest that alteronol induces cytoprotective autophagy in melanoma cells through inhibition of Akt/mTOR pathway, thus attenuates apoptosis and promotes melanoma cell EMT through TGF-β/Smad3 pathway. Combination with alteronol and autophagy inhibitor 3-MA may be a potential treatment for melanoma as it not only significantly inhibited tumor growth but also suppressed tumor invasion and migration as anti-metastasis agent.

show abstract

“…The accumulation of LC3-II can be interpreted as indicating excessive autophagosome formation or reduced degradation. To clarify this, a flux experiment was performed with a tandem mRFP-GFP-LC3 adenovirus, a reporter used to conveniently monitor and quantify autophagy flux 42 . The mRFP signal was relatively stable compared with that of GFP, since functional fusion with the lysosome allows quenching of the acid-sensitive GFP signal (Fig.…”

Section: Nnc-55 Promotes Autophagosome Formation But Blocks Distal Aumentioning

confidence: 99%

CACNA1H downregulation induces skeletal muscle atrophy involving endoplasmic reticulum stress activation and autophagy flux blockade

Hao

et al. 2020

Cell Death Dis

Self Cite

View full text Add to dashboard Cite

Multiple vaginal delivery (MVD) is an important factor for pelvic floor muscle (PFM) function decline and pelvic floor dysfunction (PFD). PFD is common in middle-aged and elderly women, but its pathogenesis is not clear. In this study, we found that the expression of CACNA1H was lower in the PFM of old mice after MVD compared with old or adult mice. In in-vitro studies, we found that treatment with the T-type Ca 2+ channel (T-channel) inhibitor NNC-55 or downregulation of the CACNA1H gene by siRNA intervention promoted myotube atrophy and apoptosis. Mechanistically, we revealed that NNC-55 increased the expression of GRP78 and DDIT3 in myotubes, indicating endoplasmic reticulum stress (ERS) activation, and that the IRE1 and PERK pathways might be involved in this effect. NNC-55 induced the formation of autophagosomes but inhibited autophagy flux. Moreover, rapamycin, an autophagy activator, did not rescue myotube atrophy or apoptosis induced by NNC-55, and the autophagy inhibitors 3-MA and HCQ accelerated this damage. Further studies showed that the ERS inhibitors 4-PBA and TUDAC relieved NNC-55-induced damage and autophagy flux blockade. Finally, we found multisite muscle atrophy and decreased muscle function in Cacna1h −/− (TH-null) mice, as well as increased autophagy inhibition and apoptotic signals in the PFM of old WT mice after MVD and TH-null mice. Taken together, our results suggest that MVD-associated PFD is partially attributed to CACNA1H downregulation-induced PFM atrophy and that ERS is a potential therapeutic target for this disease.

show abstract

Paeonol induces cytoprotective autophagy via blocking the Akt/mTOR pathway in ovarian cancer cells

Cited by 69 publications

References 45 publications

Bruceine D induces lung cancer cell apoptosis and autophagy via the ROS/MAPK signaling pathway in vitro and in vivo

Bruceine D induces lung cancer cell apoptosis and autophagy via the ROS/MAPK signaling pathway in vitro and in vivo

Autophagy inhibition potentiates the anti-EMT effects of alteronol through TGF-β/Smad3 signaling in melanoma cells

CACNA1H downregulation induces skeletal muscle atrophy involving endoplasmic reticulum stress activation and autophagy flux blockade

Contact Info

Product

Resources

About