Ampelopsin inhibits human glioma through inducing apoptosis and autophagy dependent on ROS generation and JNK pathway

Guo, Zhigang; Hu, Guozhang; Wang, Hang; Li, Zhaohui; Liu, Naijie

doi:10.1016/j.biopha.2018.12.136

Cited by 45 publications

(32 citation statements)

References 56 publications

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“…Apoptosis occurs through the extrinsic and the intrinsic pathways. 27,28 The exogenous apoptosis pathway is initiated by Caspase-8, with its activation leading to subsequent downstream cascade reactions. 29 In the intrinsic pathway, cells triggered by intracellular stimuli through the Bcl-2 protein family activate caspase-9 and caspase-3.…”

Section: Discussionmentioning

confidence: 99%

<p>Polyphyllin VI Induces Apoptosis and Autophagy via Reactive Oxygen Species Mediated JNK and P38 Activation in Glioma</p>

Liu

Chai

et al. 2020

OTT

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Background: Polyphyllin VI (PPVI), a bioactive component derived from a traditional Chinese herb Paris polyphylla, exhibits potential antitumor activity against hepatocellular carcinoma, as well as breast and lung cancers. However, its effect on glioma remains unknown. Methods: Five glioma cell lines (U251, U343, LN229, U87 and HEB) and an animal model were employed in the study. Anti-proliferation effects of PPVI were first determined using CCK-8 cell proliferation and clone formation assays, then reactive oxygen species (ROS), cell cycle progression and apoptosis effects measured by flow cytometry. The effect of PPVI on protein expression was quantified by Western blot analysis. Results: Data showed that PPVI inhibited the proliferation of glioma cell lines by modulating the G2/M phase. Additionally, incubation of cells with PPVI promoted apoptosis, autophagy, increased accumulation of ROS and activated ROS-modulated JNK and p38 pathways. On the other hand, N-acetyl cysteine, a ROS inhibitor, attenuated PPVItriggered effects. Furthermore, JNK and p38 inhibitors ameliorated PPVI-triggered autophagy and apoptosis in glioma cells. In vivo assays showed that PPVI inhibited tumor growth of U87 cell line in nude mice. Conclusion: Overall, these data suggested that PPVI might be an effective therapeutic agent for glioma.

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Section: Discussionmentioning

confidence: 99%

<p>Polyphyllin VI Induces Apoptosis and Autophagy via Reactive Oxygen Species Mediated JNK and P38 Activation in Glioma</p>

Liu

Chai

et al. 2020

OTT

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“…During the initial anti-proliferative activity screening, Amcp exhibited a potent anticancer activity against pancreatic cancer cells in vitro and was therefore chosen for the following experiments. As caspases are frequently cleaved into active components once they are activated by various cellular stimuli, we examined the protein expression of both pro- and cleaved caspase-3, and the proteolytic cleavage of PARP [ 21 , 22 ]. As shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

A novel derivative of valepotriate inhibits the PI3K/AKT pathway and causes Noxa-dependent apoptosis in human pancreatic cancer cells

et al. 2020

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Natural compound valepotriate exhibits inhibitory activity against a number of cancers, but the effect of valepotriate against pancreatic cancer is unclear, and the structure–activity relationship of valepotriate has not been characterized. In this study, we performed a structure-based similarity search and found 16 hit compounds. Among the 16 hits, (1S,6S,7R)-6-(acetyloxy)-1-[(3-methylbutanoyl)oxy]-4a,5,6,7a-tetrahydro-1H-spiro[cyclopenta[c]pyran-7,2’-oxiran]-4-ylmethyl 3-methylbutanoate (denoted as Amcp) exhibited superior anticancer activity against human pancreatic cancer BxPC-3 and SW1990 cells. The anti-proliferation activity of Amcp was validated in human pancreatic cancer BxPC-3 and SW1990 cells in vitro. Amcp more effectively induced apoptosis in BxPC-3 and SW1990 cells than gemcitabine. At a concentration of 15 μM, Amcp significantly suppressed the PI3K/AKT pathway and disrupted the mitochondrial membrane equilibrium through modulation of Noxa and Mcl-1 balance in both cell lines. Meanwhile, knockdown of Noxa substantially attenuated Amcp-induced reduction of cell viability and anti-apoptotic protein Mcl-1 level in BxPC-3 cells. In addition, Amcp showed synergistic anticancer effects when combined with gemcitabine in BxPC-3 cells. To conclude, this work not only suggests that Amcp possesses a dual-inhibitory activity towards PI3K/AKT pathway and Mcl-1, but also enlightens further development of bioactive valepotriate derivatives.

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“…Autophagy is an evolutionarily conserved mechanism responsible for cellular homeostasis in eukaryotic cells. It is a form of programmed cell death that regulates tumor development and progression ( 14 , 15 ). In addition, autophagy can have opposing roles in different cell types ( 16 ), for example activation of autophagy can contribute to the survival of human lung carcinoma A549 cells ( 17 ), or promote cell death of U251 ( 14 ) and SMMC7721 cells ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

“…It is a form of programmed cell death that regulates tumor development and progression ( 14 , 15 ). In addition, autophagy can have opposing roles in different cell types ( 16 ), for example activation of autophagy can contribute to the survival of human lung carcinoma A549 cells ( 17 ), or promote cell death of U251 ( 14 ) and SMMC7721 cells ( 15 ). Autophagy triggered in response to anticancer therapy can be associated with cell death, leading to the activation of the pro-death signaling pathway in cancer cells ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

Matrine exerts anti‑breast cancer activity by mediating apoptosis and protective autophagy via the AKT/mTOR pathway in MCF‑7 cells

Jinwen

Song

et al. 2020

Mol Med Rep

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Matrine, a major alkaloid isolated from the traditional chinese herb Sophora flavescens, has been used clinically to treat breast cancer in china. However, the effects of matrine on apoptosis and autophagy in breast cancer cells remain unclear. in the present study, the anti-breast cancer capacity of matrine was evaluated and its role in regulating apoptosis and autophagy in vitro was investigated. Matrine significantly inhibited the growth of McF-7 cells. in addition, Hoechst 33342 staining and annexin V/propidium iodide staining demonstrated that incubation with matrine induced apoptosis in McF-7 cells. Furthermore, matrine induced autophagy in McF-7 cells, manifesting as an accumulation of light chain 3 ii and downregulation of p62. additionally, matrine suppressed aKT and mammalian target of rapamycin (mTor) phosphorylation, indicating that the aKT/mTor pathway is involved in matrine-induced apoptosis and autophagy. overall, the results of the present study indicated that matrine possesses anti-breast cancer activity by providing protective autophagy via inhibition of the aKT/mTor pathway. These findings indicated that matrine may be a promising candidate for drug development targeting breast cancer.

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Ampelopsin inhibits human glioma through inducing apoptosis and autophagy dependent on ROS generation and JNK pathway

Cited by 45 publications

References 56 publications

<p>Polyphyllin VI Induces Apoptosis and Autophagy via Reactive Oxygen Species Mediated JNK and P38 Activation in Glioma</p>

<p>Polyphyllin VI Induces Apoptosis and Autophagy via Reactive Oxygen Species Mediated JNK and P38 Activation in Glioma</p>

A novel derivative of valepotriate inhibits the PI3K/AKT pathway and causes Noxa-dependent apoptosis in human pancreatic cancer cells

Matrine exerts anti‑breast cancer activity by mediating apoptosis and protective autophagy via the AKT/mTOR pathway in MCF‑7 cells

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