Sinensetin induces apoptosis and autophagy in the treatment of human T-cell lymphoma

Tan, Kok-Tong; Lin, Meng-Xian; Lin, Shih‐Chao; Tung, Yu Tang; Lin, Sheng‐Hao; Lin, Chi‐Chien

doi:10.1097/cad.0000000000000756

Cited by 23 publications

(15 citation statements)

References 31 publications

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“…Sinensetin (Sin) is a polymethoxylated flavonoid, which is found in citrus fruits and possess potent anti-inflammatory, antiangiogenesis and anticancer activities (Han Jie et al, 2021). Sin is also involved in the regulation of a variety of signaling pathways, such as NF-kappaB, AKT/mTOR and MAPKs signaling (Tan et al, 2019;Li et al, 2020). A recent study showed that Sin promotes autophagy through AMPK/mTOR signaling pathway to induce hepatocellular carcinoma cell apoptosis (Kim et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Sinensetin Reduces Osteoarthritis Pathology in the Tert-Butyl Hydroperoxide-Treated Chondrocytes and the Destabilization of the Medial Meniscus Model Mice via the AMPK/mTOR Signaling Pathway

et al. 2021

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As a common degenerative disease, osteoarthritis (OA) usually causes disability in the elderly and socioeconomic burden. Previous studies have shown that proper autophagy has a protective effect on OA. Sinensetin (Sin) is a methylated flavonoid derived from citrus fruits. Studies have shown that Sin is a good autophagy inducer and has shown excellent therapeutic effects in a variety of diseases; however, its role in the treatment of OA is not fully understood. This study proved the protective effect of Sin on OA through a series of in vivo and in vitro experiments. In vitro experiments have shown that Sin may inhibit chondrocyte apoptosis induced by tert-butyl hydroperoxide (TBHP); at the same time, it might also inhibit the production of MMP13 and promote the production of aggrecan and collagen II. Mechanism studies have shown that Sin promotes chondrocyte autophagy by activating AMPK/mTOR signaling pathway. On the contrary, inhibition of autophagy can partially abolish the protective effect of Sin on TBHP-treated chondrocytes. In vivo experiments show that Sin may protect against DMM-induced OA pathogenesis. These results provide evidence that Sin serves as a potential candidate for the treatment of OA.

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Section: Introductionmentioning

confidence: 99%

Sinensetin Reduces Osteoarthritis Pathology in the Tert-Butyl Hydroperoxide-Treated Chondrocytes and the Destabilization of the Medial Meniscus Model Mice via the AMPK/mTOR Signaling Pathway

et al. 2021

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“…In our previous study, we reported that extracts of edible plants Citrus platymamma and Citrus aurantium L. contained abundant amounts of SIN with anti-cancer and anti-inflammatory effects [ 23 ]. A recent study showed that SIN caused apoptosis and autophagy in human T-cell leukemia [ 24 ]. However, the anti-cancer effects and the molecular mechanisms of the SIN compound on HCC cells are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Sinensetin Induces Autophagic Cell Death through p53-Related AMPK/mTOR Signaling in Hepatocellular Carcinoma HepG2 Cells

Kim

Lee

et al. 2020

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Sinensetin (SIN) has been reported to exhibit anti-inflammatory and anti-cancer activity. However, the cellular and molecular mechanism by which SIN promotes hepatocellular carcinoma (HCC) cell death remains unclear. In the present study, we investigated the induction of cell death by SIN and its underlying mechanism in HepG2 cells, an HCC cell line. We found that SIN significantly induced cell death in HepG2 cells, whereas the proliferation rate of Thle2, human liver epithelial cells, was unaffected by SIN. SIN-treated HepG2 cells were not affected by apoptotic cell death; instead, autophagic cell death was induced through the p53-mediated AMPK/mTOR signaling pathway. Inhibition of p53 degradation led to both autophagy and apoptosis in HepG2 cells. p53 translocation led to SIN-induced autophagy, whereas p53 translocation inhibited SIN-induced apoptosis. However, SIN showed apoptosis in the p53-mutant Hep3B cell line. Molecular docking simulation of the p53 core domain showed effective binding with SIN, which was found significant compared with the known p53 activator, RITA. Collectively, these data suggest that SIN may be a potential anti-cancer agent targeting autophagic cell death in human liver cancer.

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“…Sinensetin was found to significantly impede Jurkat cell proliferation and additionally triggered apoptosis and autophagy ( Tan et al, 2019 ). Human T-cell acute lymphoblastic leukemia, CCRF-CEM, non-Hodgkin’s lymphoma cell line, Jurkat cell and mouse primary T-cells isolated and purified from six week-old male BALB/c mice were used in this study.…”

Section: Introductionmentioning

confidence: 99%

“…In the same study, sinensetin downregulated phosphorylation of Akt and mTOR dose-dependently. Inhibition of those two tremendously led Jurkat cells to be more sensitive to cytotoxicity effect of sinensetin in Jurkat cells, suggest that co-treatment of sinensetin with Akt and mTOR inhibitor synergistically blocked Akt/mTOR signaling pathway ( Tan et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Sinensetin: An Insight on Its Pharmacological Activities, Mechanisms of Action and Toxicity

et al. 2021

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Sinensetin, a plant-derived polymethoxylated flavonoid found in Orthosiphon aristatus var. aristatus and several citrus fruits, has been found to possess strong anticancer activities and a variety of other pharmacological benefits and promising potency in intended activities with minimal toxicity. This review aims to compile an up-to-date reports of published scientific information on sinensetin pharmacological activities, mechanisms of action and toxicity. The present findings about the compound are critically analyzed and its prospect as a lead molecule for drug discovery is highlighted. The databases employed for data collection are mainly through Google Scholar, PubMed, Scopus and Science Direct. In-vitro and in-vivo studies showed that sinensetin possessed strong anticancer activities and a wide range of pharmacological activities such as anti-inflammatory, antioxidant, antimicrobial, anti-obesity, anti-dementia and vasorelaxant activities. The studies provided some insights on its several mechanisms of action in cancer and other disease states. However, more detail mechanistic studies are needed to understand its pharmacological effects. More in vivo studies in various animal models including toxicity, pharmacokinetic, pharmacodynamic and bioavailability studies are required to assess its efficacy and safety before submission to clinical studies. In this review, an insight on sinensetin pharmacological activities and mechanisms of action serves as a useful resource for a more thorough and comprehensive understanding of sinensetin as a potential lead candidate for drug discovery.

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Sinensetin induces apoptosis and autophagy in the treatment of human T-cell lymphoma

Cited by 23 publications

References 31 publications

Sinensetin Reduces Osteoarthritis Pathology in the Tert-Butyl Hydroperoxide-Treated Chondrocytes and the Destabilization of the Medial Meniscus Model Mice via the AMPK/mTOR Signaling Pathway

Sinensetin Reduces Osteoarthritis Pathology in the Tert-Butyl Hydroperoxide-Treated Chondrocytes and the Destabilization of the Medial Meniscus Model Mice via the AMPK/mTOR Signaling Pathway

Sinensetin Induces Autophagic Cell Death through p53-Related AMPK/mTOR Signaling in Hepatocellular Carcinoma HepG2 Cells

Sinensetin: An Insight on Its Pharmacological Activities, Mechanisms of Action and Toxicity

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