Rutin induces autophagy in cancer cells

Park, Mi Hee; Kim, Seyeon; Song, Yuri; Kim, Su-Mi; Kim, Hyung‐Joon; Na, Hee Sam; Chung, Jin

doi:10.11620/ijob.2016.41.1.045

Cited by 13 publications

(5 citation statements)

References 18 publications

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“…Nabavi et al reported that polyphenols can regulate autophagy [34]. Another study reported that rutin induced autophagy in oral (CA9-22) and lung (A549) cancer cells [35]. Similarly, our findings indicate that rutin in MLPE regulates autophagy in HepG2 cells by influencing p53 signaling (Figure 5).…”

Section: Discussionsupporting

confidence: 80%

Mulberry Leaf Polyphenol Extract and Rutin Induces Autophagy Regulated by p53 in Human Hepatoma HepG2 Cells

Tsai

Wang

et al. 2021

Pharmaceuticals

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The edible leaves of the mulberry (Morus alba L.) plant are used worldwide. They contain abundant polyphenolic compounds with strong anticancer properties. We previously revealed that apoptosis was mediated in p53-negative Hep3B cells, and mulberry leaf polyphenol extract (MLPE) induced autophagy in p53-transfected Hep3B cells. However, how this autophagy is induced by p53 in human hepatoma HepG2 (p53 wild type) cells remains unclear. In the current study, MLPE induced autophagy, as demonstrated by enhanced acidic vesicular organelle staining, by upregulating beclin-1, increasing LC3-II conversion, and phosphorylating AMPK. In HepG2 cells, these processes were associated with p53. Western blot also revealed phosphatidylinositol-3 kinase (PI3K), p-AKT, and fatty acid synthase (FASN) suppression in MLPE-treated cells. Moreover, treatment with the p53 inhibitor pifithrin-α (PFT-α) inhibited autophagy and increased apoptotic response in MLPE-treated HepG2 cells. PFT-α treatment also reversed MLPE-induced PI3K, p-AKT, and FASN suppression. Thus, co-treatment with MLPE and PFT-α significantly increased caspase-3, caspase-8, and cytochrome c release, indicating that p53 deficiency caused the apoptosis. In addition, rutin, a bioactive polyphenol in MLPE, may affect autophagy in HepG2 cells. This study demonstrates that MLPE is a potential anticancer agent targeting autophagy and apoptosis in cells with p53 status. Moreover, this work provides insight into the mechanism of p53 action in MLPE-induced cytotoxicity in hepatocellular carcinoma.

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Section: Discussionsupporting

confidence: 80%

Mulberry Leaf Polyphenol Extract and Rutin Induces Autophagy Regulated by p53 in Human Hepatoma HepG2 Cells

Tsai

Wang

et al. 2021

Pharmaceuticals

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“…It should be mentioned that the effect of Rut on the autophagy function is controversial. Park et al [41] revealed that Rut enhanced autophagy of cancer cells, while others have shown that Rut contributes to combating neurodegeneration by repressing the autophagy process via mechanisms such as preventing 1-methyl-4-phenylpyridinium-induced autophagy [12] and polyQmediated neuronal death [42]. Additionally, Rut could successfully alleviate doxorubicin-induced cardiotoxicity as well [43,44].…”

Section: Discussionmentioning

confidence: 99%

Solid Lipid Nanoparticles Enhance Protective Effect of Rutin against STZ-Induced Neurotoxicity in PC12 Cells through Autophagy Suppression

Nouri

Sajadimajd

Bahrami

et al. 2022

Journal of Nanomaterials

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Rutin (Rut) has been identified as a neuroprotective compound with displayed beneficial effects in Alzheimer’s disease. However, low bioavailability and solubility are the major concerns pertaining to the use of Rut. Aberrant function of autophagy has been found as a well-established participant in the pathogenesis of neuronal degeneration. In the present study, Rut and Rut-loaded solid lipid nanoparticles (Rut-SLNs) were used to protect rat PC12 cells against streptozotocin- (STZ-) induced neurotoxicity. Rut-SLNs were fabricated by a solvent evaporation-ultrasonic method. Depending on the experimental patterns including pretreatment, cotreatment, and posttreatment, PC12 cells were exposed to STZ and desired doses of the SLNs, Rut, and Rut-SLNs. The viability of the cells, the mitochondrial membrane potential (MMP), and the expression of miR-21, miR-22, Akt, ATG5, Beclin1, and LC3 were evaluated by using MTT assay, rhodamine 123 fluorescent dye, and qRT-PCR, respectively. SLN and Rut-SLNs possess the smooth surface with an average size of 117.2 and 176.9 nm, respectively, with a negative zeta potential. The encapsulation efficiency and loading capacity of Rut in SLNs were 90.32% and 49.1%, respectively. The nanoformulation revealed a sustained drug release in vitro up to 72 h and followed Higuchi kinetics. Rut-SLNs displayed a neuroprotective effect by augmenting the viability of PC12 cells and increasing MMP. In addition, Rut-SLNs suppressed autophagy which was stimulated by STZ whereas, the free Rut demonstrated lower effect. Taken together, these results clearly indicated that Rut-SLNs could be a good candidate for the prevention of neurodegenerative diseases.

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“…Rutin treatment has also resulted in an enhanced expression level of Beclin1 and has triggered the formation of the ATG5/12 complex. LC3-II (hallmark of autophagy) activation was also observed in rutin-treated cancer cells, thereby leading to autophagy-mediated cancer cell death [57].…”

Section: Rutin's Targeting Of Apoptotic Pathways and Autophagy Signaling Moleculesmentioning

confidence: 99%

Rutin (Bioflavonoid) as Cell Signaling Pathway Modulator: Prospects in Treatment and Chemoprevention

et al. 2021

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Cancer is a complex ailment orchestrated by numerous intrinsic and extrinsic pathways. Recent research has displayed a deep interest in developing plant-based cancer therapeutics for better management of the disease and limited side effects. A wide range of plant-derived compounds have been reported for their anticancer potential in the quest of finding an effective therapeutic approach. Rutin (vitamin P) is a low-molecular weight flavonoid glycoside (polyphenolic compound), abundantly present in various vegetables, fruits (especially berries and citrus fruits), and medicinal herbs. Numerous studies have delineated several pharmacological properties of rutin such as its antiprotozoal, antibacterial, anti-inflammatory, antitumor, antiviral, antiallergic, vasoactive, cytoprotective, antispasmodic, hypolipidemic, antihypertensive, and antiplatelet properties. Specifically, rutin-mediated anticancerous activities have been reported in several cancerous cell lines, but the most common scientific evidence, encompassing several molecular processes and interactions, including apoptosis pathway regulation, aberrant cell signaling pathways, and oncogenic genes, has not been thoroughly studied. In this direction, we attempted to project rutin-mediated oncogenic pathway regulation in various carcinomas. Additionally, we also incorporated advanced research that has uncovered the notable potential of rutin in the modulation of several key cellular functions via interaction with mRNAs, with major emphasis on elucidating direct miRNA targets of rutin as well as the process needed to transform these approaches for developing novel therapeutic interventions for the treatment of several cancers.

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Rutin induces autophagy in cancer cells

Cited by 13 publications

References 18 publications

Mulberry Leaf Polyphenol Extract and Rutin Induces Autophagy Regulated by p53 in Human Hepatoma HepG2 Cells

Mulberry Leaf Polyphenol Extract and Rutin Induces Autophagy Regulated by p53 in Human Hepatoma HepG2 Cells

Solid Lipid Nanoparticles Enhance Protective Effect of Rutin against STZ-Induced Neurotoxicity in PC12 Cells through Autophagy Suppression

Rutin (Bioflavonoid) as Cell Signaling Pathway Modulator: Prospects in Treatment and Chemoprevention

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