Melatonin‐mediated regulation of autophagy: Making sense of double‐edged sword in cancer

Mirza-Aghazadeh-Attari, Mohammad; Mohammadzadeh, Amir; Adib, Ali; Darband, Saber Ghazizadeh; Sadighparvar, Shirin; Mihanfar, Ainaz; Majidinia, Maryam; Yousefi, Bahman

doi:10.1002/jcp.28435

Cited by 16 publications

(6 citation statements)

References 147 publications

(202 reference statements)

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“…Recent studies suggest autophagy is a double-edged sword in tumourigenesis and metastasis. Autophagy can serve as a pro-survival or pro-death stress response in different conditions [27][28][29]. Recent evidence has shown that autophagy is involved in various immune processes and plays an important role in regulating the release of inflammatory cytokines and the pathological process of bone destruction in RA [30,31].…”

Section: Discussionmentioning

confidence: 99%

Resveratrol promotes apoptosis and G2/M cell cycle arrest of fibroblast-like synoviocytes in rheumatoid arthritis through regulation of autophagy and the serine-threonine kinase-p53 axis

Gan

et al. 2021

Arch Med Sci

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IntroductionResveratrol, a polyphenol extracted from many plant species, has emerged as a promising pro-apoptotic agent in various cancer cells. However, the role of resveratrol in cell proliferation and apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis (RA-FLS) is not fully understood. The study was aimed at elucidating the role of resveratrol in cell proliferation and apoptosis of RA-FLS and the underlying molecular mechanism.Material and methodsCultured RA-FLSs were subjected to tumour necrosis factor  (TNF-). The cell proliferation was measured by Cell Counting Kit-8 assay. Cell apoptosis and cell cycle of RA-FLSs were determined by flow cytometry. The levels of apoptosis or autophagy or cell cycle-related protein were detected by immunoblot analysis.ResultsIn our study, we confirmed that resveratrol reversed TNF- mediated cell proliferation in RA-FLS. Meanwhile, resveratrol blocked cells at the G2/M stage and reduced the ratio of S phase cells through upregulation of p53 and consequently led to apoptotic cell death. Quite interestingly, we found that resveratrol reversed TNF--induced autophagy. Inhibition of autophagy by resveratrol or autophagy inhibitor or Beclin-1 siRNA suppressed TNF- mediated cell survival and promoted cell apoptosis. However, the autophagy inducer rapamycin (RAPA) reversed the effect of resveratrol on autophagy and cell proliferation. Mechanistic studies revealed that resveratrol inhibited the activation of the phosphoinositide 3-kinases/serine-threonine kinase (PI3K/AKT) pathway. Inhibition of PI3K/AKT pathway by inhibitor LY294002 or resveratrol increased the expression of p53 and decreased the expression of cycle protein (cyclin B1), which further led to block cells in the G2/M arrest.ConclusionsOur preliminary study indicated that resveratrol may suppress RA-FLS cell survival and promote apoptosis at least partly through regulation of autophagy and the AKT-p53 axis.

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Section: Discussionmentioning

confidence: 99%

Resveratrol promotes apoptosis and G2/M cell cycle arrest of fibroblast-like synoviocytes in rheumatoid arthritis through regulation of autophagy and the serine-threonine kinase-p53 axis

Gan

et al. 2021

Arch Med Sci

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“…Inhibiting the protective effect of autophagy, blocking the degradation process of substrates and promoting apoptosis (Li et al, 2013;Wang et al, 2013;Cho et al, 2018). Autophagy is a biological process with multifaceted effects, which can promote cell survival and induce death (Jiang et al, 2019;Mirza-Aghazadeh-Attari et al, 2019). However, the nature of autophagy remains unclear in many studies, and needs to be further explored.…”

Section: Discussion and Prospectmentioning

confidence: 99%

Matrine: A Promising Natural Product With Various Pharmacological Activities

et al. 2020

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Matrine is an alkaloid isolated from the traditional Chinese medicine Sophora flavescens Aiton. At present, a large number of studies have proved that matrine has an anticancer effect can inhibit cancer cell proliferation, arrest cell cycle, induce apoptosis, and inhibit cancer cell metastasis. It also has the effect of reversing anticancer drug resistance and reducing the toxicity of anticancer drugs. In addition, studies have reported that matrine has a therapeutic effect on Alzheimer's syndrome, encephalomyelitis, asthma, myocardial ischemia, rheumatoid arthritis, osteoporosis, and the like, and its mechanism is mainly related to the inhibition of inflammatory response and apoptosis. Its treatable disease spectrum spans multiple systems such as the nervous system, circulatory system, and immune system. The antidisease effect and mechanism of matrine are diverse, so it has high research value. This review summarizes recent studies on the pharmacological mechanism of matrine, with a view to providing reference for subsequent research.

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“…When cells are under stress conditions such as starvation, they use autophagy to degrade damaged or unnecessary cellular organelles or proteins for recycling to maintain cell homeostasis. 25,26 Researchers found that cancer cells use autophagy to supply energy and develop resistance to anticancer drugs; therefore, inhibiting autophagy may promote cancer cell death and help overcome drug resistance. 27,28 In this study, we showed for the first time that the circRNA hsa_circ_0003489 was essential for maintaining the viability of MM cells and may also contribute to the development of resistance to BTZ by regulating the balance between autophagy and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of hsa_circ_0003489 shifts balance from autophagy to apoptosis and sensitizes multiple myeloma cells to bortezomib via miR‐874‐3p/HDAC1 axis

Tian

Chen

Zhu

et al. 2021

The Journal of Gene Medicine

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Background: Circular RNAs (circRNAs) crucially regulate tumor progression. In this study, we examined the functional roles and mechanisms of hsa_circ_0003489 in multiple myeloma (MM).Methods: Upon altering the expressions of hsa_circ_0003489, miR-874-3p, and/or histone deacetylase 1 (HDAC1) in MM1.R cells and treating them with bortezomib (BTZ), cell viability was examined by CCK-8 assay; cell proliferation by Ki-67 immunofluorescence; apoptosis by TUNEL staining, flow cytometry, and western blot; and autophagy by electron microscopy and western blot. The interaction between hsa_circ_0003489 and miR-874-3p as well as that between miR-874-3p and HDAC1 was examined by expressional analysis, dual luciferase reporter assay, and RNA immunoprecipitation. The in vivo impacts of hsa_circ_0003489 on MM growth and sensitivity to BTZ were examined using an MM xenograft mouse model.Results: Knocking down hsa_circ_0003489 significantly inhibited the viability, cell proliferation, and autophagy, while promoting the apoptosis of MM cells in vitro and MM xenograft in vivo. Suppressing hsa_circ_0003489 also further boosted the cytotoxic effects of BTZ in MM cells and reversed its promoting effect on autophagy.Mechanically, hsa_circ_0003489 acted as a sponge of miR-874-3p and positively regulated the expression of miR-874-3p target, HDAC1. MiR-874-3p and HDAC1 essentially mediated the effects of hsa_circ_0003489 on cell viability, proliferation, apoptosis, and autophagy. Conclusion:The hsa_circ_0003489/miR-874-3p/HDAC1 axis critically regulates the balance between apoptosis and autophagy. Silencing hsa_circ_0003489 sensitizes MM cells to BTZ by inhibiting autophagy and thus may boost the therapeutic effects of BTZ.

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Melatonin‐mediated regulation of autophagy: Making sense of double‐edged sword in cancer

Cited by 16 publications

References 147 publications

Resveratrol promotes apoptosis and G2/M cell cycle arrest of fibroblast-like synoviocytes in rheumatoid arthritis through regulation of autophagy and the serine-threonine kinase-p53 axis

Resveratrol promotes apoptosis and G2/M cell cycle arrest of fibroblast-like synoviocytes in rheumatoid arthritis through regulation of autophagy and the serine-threonine kinase-p53 axis

Matrine: A Promising Natural Product With Various Pharmacological Activities

Inhibition of hsa_circ_0003489 shifts balance from autophagy to apoptosis and sensitizes multiple myeloma cells to bortezomib via miR‐874‐3p/HDAC1 axis

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