Maslinic acid promotes autophagy by disrupting the interaction between Bcl2 and Beclin1 in rat pheochromocytoma PC12 cells

Dong, Xiaoli; Zhang, Jiaxiao; Zhou, Zongqing; Ye, Zhen-Nan; Yuan, Jifan; Cao, Fengjun; Wang, Xuanbin; Liu, Wenchao; Yu, Wenxuan; Li, Xiaohua

doi:10.18632/oncotarget.20210

Cited by 15 publications

(7 citation statements)

References 45 publications

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“…Furthermore, we confirmed that HET was capable of inducing liver autophagy in the aged FR mice as assessed by the increased number of autophagic vacuoles and significantly increased expression of autophagy-related genes. Although the detailed mechanism underlying the responses to HET is unclear, compounds that increase Beclin1 expression 40 and block the Beclin1–Bcl-2 interaction 43 may contribute to its mechanism of action. Therefore, HET could alleviate the disruption of energy homeostasis during the aging process by mainly inducing liver autophagy, but not anti-inflammatory effects.…”

Section: Discussionmentioning

confidence: 99%

Bcl-2-dependent autophagy disruption during aging impairs amino acid utilization that is restored by hochuekkito

et al. 2021

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Chronic undernutrition contributes to the increase in frailty observed among elderly adults, which is a pressing issue in the sector of health care for older people worldwide. Autophagy, an intracellular recycling system, is closely associated with age-related pathologies. Therefore, decreased autophagy in aging could be involved in the disruption of energy homeostasis that occurs during undernutrition; however, the physiological mechanisms underlying this process remain unknown. Here, we showed that 70% daily food restriction (FR) induced fatal hypoglycemia in 23–26-month-old (aged) mice, which exhibited significantly lower hepatic autophagy than 9-week-old (young) mice. The liver expressions of Bcl-2, an autophagy-negative regulator, and Beclin1–Bcl-2 binding, were increased in aged mice compared with young mice. The autophagy inducer Tat-Beclin1 D11, not the mTOR inhibitor rapamycin, decreased the plasma levels of the glucogenic amino acid and restored the blood glucose levels in aged FR mice. Decreased liver gluconeogenesis, body temperature, physical activity, amino acid metabolism, and hepatic mitochondrial dynamics were observed in the aged FR mice. These changes were restored by treatment with hochuekkito that is a herbal formula containing several autophagy-activating ingredients. Our results indicate that Bcl-2 upregulation in the liver during the aging process disturbs autophagy activation, which increases the vulnerability to undernutrition. The promotion of liver autophagy may offer clinical therapeutic benefits to frail elderly patients.

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Section: Discussionmentioning

confidence: 99%

Bcl-2-dependent autophagy disruption during aging impairs amino acid utilization that is restored by hochuekkito

et al. 2021

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“…In the last decade, most studies focused on the anti-cancer activity of MA, because this compound exerts anti-proliferative and pro-apoptotic effects 26–28 . Of interest, doses of more than 100 µM MA have been shown to suppress cell growth and to induce apoptosis, whereas low doses of <100 µM solely affect the proliferation rate of tumor cells 29 .…”

Section: Discussionmentioning

confidence: 99%

Maslinic acid alleviates ischemia/reperfusion-induced inflammation by downregulation of NFκB-mediated adhesion molecule expression

Ampofo

Berg

Menger

et al. 2019

Sci Rep

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Ischemia/reperfusion (I/R)-induced inflammation is associated with enhanced leukocyte rolling, adhesion and transmigration within the microcirculation. These steps are mediated by hypoxia-triggered signaling pathways, which upregulate adhesion molecule expression on endothelial cells and pericytes. We analyzed whether these cellular events are affected by maslinic acid (MA). Mitochondrial activity and viability of MA-exposed endothelial cells and pericytes were assessed by water-soluble tetrazolium (WST)-1 and lactate dehydrogenase (LDH) assays as well as Annexin V/propidium iodide (PI) stainings. Effects of MA on hypoxia and reoxygenation-induced expression of E-selectin, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 were determined by flow cytometry. The subcellular localization of the NFκB subunit p65 was analyzed by immunofluorescence and Western blot. I/R-induced leukocytic inflammation was studied in MA- and vehicle-treated mouse dorsal skinfold chambers by intravital fluorescence microscopy and immunohistochemistry. MA did not affect viability, but suppressed the mitochondrial activity of endothelial cells. Furthermore, MA reduced adhesion molecule expression on endothelial cells and pericytes due to an inhibitory action on NFκB signaling. Numbers of adherent and transmigrated leukocytes were lower in post-ischemic tissue of MA-treated mice when compared to vehicle-treated controls. In addition, MA affected reactive oxygen species (ROS) formation, resulting in a diminished oxidative DNA damage. Hence, MA represents an attractive compound for the establishment of novel therapeutic approaches against I/R-induced inflammation.

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“…The sample preparation has been described previously [31]. Briefly, drug-treated HCT 116 cells on coverslips were fixed in freshly-prepared 4% paraformaldehyde, permeabilized with 0.1% Triton X-100, and blocked with 3% BSA (Bovine Serum Albumin, BSA) in PBS (phosphate buffer saline, PBS).…”

Section: Methodsmentioning

confidence: 99%

Physalis peruviana-Derived 4β-Hydroxywithanolide E, a Novel Antagonist of Wnt Signaling, Inhibits Colorectal Cancer In Vitro and In Vivo

Yuan

Liu

et al. 2019

Molecules

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Deregulation of the Wnt signaling pathway leads to colorectal cancer progression. Natural dietary compounds serve as promising candidates for development as chemopreventive agents by suppressing the Wnt/β-catenin signaling pathway. Physalis peruviana-derived 4βHWE showed a significant inhibitory activity with a calculated IC50 of 0.09 μΜ in a screening of novel inhibitors of Wnt signaling with the dual-luciferase reporter assay. This study investigated the anti-tumor effect of 4βHWE and the potential Wnt signaling inhibitory mechanism. Both the western blot analysis and immunofluorescence assay showed that 4βHWE promoted the phosphorylation and degradation of β-catenin and the subsequent inhibition of its nuclear translocation to attenuate the endogenous Wnt target gene expression in colorectal cancer (CRC) cells. The cell viability assay indicated that 4βHWE preferentially inhibited the proliferation of CRC compared with CCD-841-CoN, a normal human colonic epithelial cell line. 4βHWE-mediated G0/G1 cell cycle arrest and apoptosis induction contributed to the suppression of the proliferation of CRC in the cell cycle and Annexin V-FITC/Propidium Iodide apoptosis analysis. Moreover, in vivo, 4βHWE dramatically inhibited tumor growth in HCT116 xenografts by attenuating the Wnt/β-catenin signaling pathway. In conclusion, our study suggested that 4βHWE could be of potential use in anti-tumor agent development as a novel Wnt signaling inhibitor.

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Maslinic acid promotes autophagy by disrupting the interaction between Bcl2 and Beclin1 in rat pheochromocytoma PC12 cells

Cited by 15 publications

References 45 publications

Bcl-2-dependent autophagy disruption during aging impairs amino acid utilization that is restored by hochuekkito

Bcl-2-dependent autophagy disruption during aging impairs amino acid utilization that is restored by hochuekkito

Maslinic acid alleviates ischemia/reperfusion-induced inflammation by downregulation of NFκB-mediated adhesion molecule expression

Physalis peruviana-Derived 4β-Hydroxywithanolide E, a Novel Antagonist of Wnt Signaling, Inhibits Colorectal Cancer In Vitro and In Vivo

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