Sulforaphane promotes ER stress, autophagy, and cell death: implications for cataract surgery

Liu, Hanruo; Smith, Alan; Ball, Sarah; Bao, Yongping; Bowater, Richard P.; Wang, Ke; Wormstone, I. Michael

doi:10.1007/s00109-016-1502-4

Cited by 31 publications

(37 citation statements)

References 46 publications

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“…To investigate whether sulforaphane is reducing the cell growth or encourages cell death, a study was conducted in human lens cell line and reported that sulforaphane reduced the cell viability in human lens cell line and promotes cell death. The study also revealed that sulforaphane promotes ER stress and autophagy induction via MAPK signaling [103] , and longer treatment with sulforaphane has shown significant decrease in AMPK phosphorylation at thr-172 [104] in human prostate cancer cells.…”

Section: Sulforaphanementioning

confidence: 80%

Targeting autophagy with small molecules for cancer therapy

Kondapuram¹,

Sarvagalla²,

Coumar³

2019

JCMT

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Autophagy is a conserved lysosomal-dependent catabolic process that maintains the cellular homeostasis by recycling misfolded proteins and damaged organelles. It involves a series of ordered events (initiation, nucleation, elongation, lysosomal fusion and degradation) that are tightly regulated/controlled by diverse cell signals and stress. It is like a double-edged sword that can play either a protective or destructive role in cancer, by pro-survival or apoptotic cues. Recently, modulating autophagy by pharmacological agents has become an attractive strategy to treat cancer. Currently, a number of small molecules that inhibit autophagy initiation (e.g., ULK kinase inhibitors), nucleation (e.g., Vps34 inhibitors), elongation (e.g., ATG4 inhibitors) and lysosome fusion (e.g., chloroquine, hydroxyl chloroquine, etc .) are reported in pre-clinical and clinical study. Also a number of small molecules reported to induce autophagy by targeting mammalian target of rapamycin (e.g., rapamycin analogs) or adenosine 5'-monophosphateactivated protein kinase (e.g., sulforaphane). The study results suggest that many potential "druggable" targets exist in the autophagy pathway that could be harnessed for developing new cancer therapeutics. In this review, we discuss the reported autophagy modulators (inhibitors and inducers), their molecular mode of action and their applications in cancer therapy.

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Section: Sulforaphanementioning

confidence: 80%

Targeting autophagy with small molecules for cancer therapy

Kondapuram¹,

Sarvagalla²,

Coumar³

2019

JCMT

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“…Apoptosis of lens epithelial cells (LEC cell) is also the basis of pathophysiological and pathophysiological changes in cataract . In addition, autophagy is a highly conserved process in cell self‐renewal and human lens cells mainly degrade the senescent organelles and the proteins through autophagy to maintain the transparency of lenses . Therefore, it is fundamental to investigate the regulation of apoptosis and autophagy in cataract.…”

Section: Introductionmentioning

confidence: 99%

miR‐23b‐3p regulates apoptosis and autophagy via suppressing SIRT1 in lens epithelial cells

Zhou

Wang

et al. 2019

J of Cellular Biochemistry

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Age-related cataract is one of the prior causes of blindness and the incidence rates of cataract are even rising. Oxidative stress plays an important role in the pathogenesis of cataracts. Under oxidative stress, lens epithelial cell (LEC cell) apoptosis is activated, which might lead to the opacity of the lens and accelerate the progression of cataract development. Meanwhile, autophagy is also active to face oxidative stress. miRNAs have been reported to involve cataract. However, the underlying mechanism is not clear. The present study aimed to investigate the regulatory effect of miR23b-3p on apoptosis and autophagy in LEC cells under oxidative stress. The expression levels of miR-23b-3p were examined in age-related cataract tissues and LEC cells treated with hydrogen peroxide, showing that miR23b-3p expression levels were upregulated. Knockdown of miR23b-3p expression in LEC cells brought about apoptosis significantly decreased while autophagy significantly increased during hydrogen peroxide.We predicted microRNA miRNA-23b-3p might participate in regulating silent information regulator 1 (SIRT1) by bioinformatics database of TargetScan. Luciferase reporter assays confirmed that miRNA-23b-p could suppress SIRT1 expression by binding its 3′UTR. In addition, overexpression or knockdown of miR-23b-3p could decrease or increase SIRT1 expression, which indicated that Mir-23b-3p could suppress SIRT1 expression. In addition, enhanced SIRT1 could attenuate the regulation of cell apoptosis and autophagy induced by overexpression of miR-23b-3p. Taken together, our findings revealed that miR-23b-3p regulated apoptosis and autophagy via suppressing SIRT1 in LEC cell under oxidative stress, which could provide new ideas for clinical treatment of cataract. K E Y W O R D Sapoptosis, autophagy, cataract, miR-23b-p, SIRT1

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“…In addition to the cytoprotective effect, SFN has also been shown to exhibit cytotoxic effects including promoting ER stress and cell death [11][12][13] ; disrupting mitochondria 14 , tubulin and microtubule function [15][16][17] ; inducing DNA damage 18 , apoptosis and cell cycle arrest [19][20][21][22] ; inhibiting telomerase activity 11,23 and protein-protein interaction in Hsp90 complex 24 . The complex bioactivities of SFN and subsequent cellular responses are highly dependent upon the dose and duration of SFN treatment.…”

Section: Introductionmentioning

confidence: 99%

Antioxidant effects of sulforaphane in human HepG2 cells and immortalised hepatocytes

Liu

Wang

Tang

et al. 2019

Food and Chemical Toxicology

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Sulforaphane (SFN) has shown anti-cancer effects in cellular and animal studies but its effectiveness has been limited in human studies. Here, the effects of SFN were measured in both human hepatocyte (HHL5) and hepatoma (HepG2) cells. Results showed that SFN inhibited cell viability and induced DNA strand breaks at high doses (≥ 20 µM). It also activated the nuclear factor (erythroidderived 2)-like 2 (Nrf2), and increased intracellular glutathione (GSH) levels at 24 hours. Pretreatment with a low dose SFN (≤5 µM) protected against hydrogen peroxide (H 2 O 2)-induced cell damage. High doses of SFN were more toxic towards HHL5 compared to HepG2 cells; the difference is likely due to the disparity in the responses of Nrf2-driven enzymes and-GSH levels between the two cell lines. In addition, HepG2 cells hijacked the cytoprotective effect of SFN over a wider dose range (1.25-20 µM) compared to HHL5. Manipulation of levels of GSH and Nrf2 in HepG2 cells confirmed that both molecules mediate the protective effects of SFN against H 2 O 2. The non-specific nature of SFN in the regulation of cell death and survival could present undesirable risks, i.e. be more toxic to normal cells, and cause chemo-resistance in tumor cells. These issues should be addressed in the context for cancer prevention and treatment before large scale clinical trials are undertaken.

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Sulforaphane promotes ER stress, autophagy, and cell death: implications for cataract surgery

Cited by 31 publications

References 46 publications

Targeting autophagy with small molecules for cancer therapy

Targeting autophagy with small molecules for cancer therapy

miR‐23b‐3p regulates apoptosis and autophagy via suppressing SIRT1 in lens epithelial cells

Antioxidant effects of sulforaphane in human HepG2 cells and immortalised hepatocytes

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