Functional proteomic analysis revels that the ethanol extract of Annona muricata L. induces liver cancer cell apoptosis through endoplasmic reticulum stress pathway

Liu, Na; Yang, Hua; Wang, Pu; Lü, Yu; Yang, Ying Juan; Wang, Lan; Lee, Shao Chin

doi:10.1016/j.jep.2016.05.045

Cited by 61 publications

(50 citation statements)

References 26 publications

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“…For example, extracts of Annona muricata can cause apoptosis of cancer cells and inhibit tumor growth through the activation of ERS pathway, with the upregulation of GRP94, HSP70, Bip and CHOP, as well as the upregulated phosphorylation of PERK and eIF2α [32]. Andrographolide induces apoptosis of colon cancer cells via the upregulation of ERS proteins GRP78, CHOP as well as the decreased BAX/Bcl-2 ration [33].…”

Section: Discussionmentioning

confidence: 99%

MiR-410 Acts as a Tumor Suppressor in Estrogen Receptor-Positive Breast Cancer Cells by Directly Targeting ERLIN2 via the ERS Pathway

Guo

et al. 2018

Cell Physiol Biochem

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Background/Aims: Endoplasmic reticulum lipid raft-associated 2 (ERLIN2) is reported to be overexpressed in human breast cancer cells and plays an important role in cell proliferation. MicroRNAs (miRNAs) act as post-transcriptional regulators of gene expression and are involved in the development of multiple malignancies, including breast cancer. However, the molecular mechanism of the aberrant ERLIN2 expression in human breast cancer remains poorly understood. Methods: MiR-410 expression level was analyzed using Real-time PCR, and ERLIN2 expression was analyzed using Western blot, Real-time PCR and immunohistochemical staining. The effect of miR-410 on ERLIN2 3’UTR intensity was performed using a luciferase assay. Cell proliferation was analyzed using CCK-8 and colony formation assay, together with an Annexin V-PE/7-AAD kit for cell apoptosis assay. Cell migration and invasion was detected using a Transwell migration and invasion assay. Methylation specific PCR was used to examine whether miR-410 promoter was demethylated. Results: In this study, we validated that ERLIN2 was a direct target of miR-410 and miR-410 suppressed ERLIN2 expression at the post-transcriptional level. Importantly, the regulation of ERLIN2 by miR-410 was estrogen receptor (ER) dependent. Functional studies demonstrated that miR-410 inhibited breast cancer cell proliferation, migration and invasion, but promoted cell apoptosis. However, inhibition of miR-410 resulted in opposite effects. A xenograft nude mouse model further confirmed that miR-410 suppressed breast tumor growth. In addition, miR-410 modulated the expression levels of epithelial-mesenchymal transition (EMT)-related genes. ERLIN2 knockdown suppressed cell proliferation, migration and invasion, as well as EMT. ERLIN2 overexpression can restore the cell proliferation, migration and invasion that were inhibited by miR-410. Furthermore, our data demonstrated that miR-410 inhibition suppressed the expression of endoplasmic reticulum-stress (ERS)-related genes, while ERLIN2 knockdown abrogated the effects of miR-410 inhibitor. Finally, we showed that miR-410 was downregulated in human ER-positive breast cancer tissues, inversely correlated with ERLIN2. We further demonstrated the downregulation of miR-410 in breast cancer might be due to the hypermethylation of its promoter. Conclusions: Our study indicates that miR-410 suppresses cell growth, migration and invasion by directly downregulating ERLIN2 in ER positive breast cancer, acting as a tumor suppressor. Our study also suggests that miR-410 may serve as a potential therapeutic target for patients with ER positive breast cancer.

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Section: Discussionmentioning

confidence: 99%

MiR-410 Acts as a Tumor Suppressor in Estrogen Receptor-Positive Breast Cancer Cells by Directly Targeting ERLIN2 via the ERS Pathway

Guo

et al. 2018

Cell Physiol Biochem

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“…The analysis of the mechanism of action revealed that growth‐inhibition activity is associated with the disruption of membrane mitochondrial potential, ROS generation, and G 0 /G 1 cell arrest. An involvement of the apoptotic pathway was also identified for A. muricata in liver cancer Hep G2 cells . The extract reduced cell viability and elicited apoptosis via the upregulation of HSP70, GRP94, and DPI‐related protein 5 expression.…”

Section: Extracts From Annona Speciesmentioning

confidence: 84%

“…An involvement of the apoptotic pathway was also identified for A. muricata in liver cancer Hep G2 cells. 12 The extract reduced cell viability and elicited apoptosis via the upregulation of HSP70, GRP94, and DPIrelated protein 5 expression.…”

Section: Extracts From Annona Speciesmentioning

confidence: 97%

Annona species (Annonaceae): a rich source of potential antitumor agents?

Tundis

Xiao

Loizzo

2017

Annals of the New York Academy of Sciences

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Plants have provided the basis of traditional medicine systems throughout the world for thousands of years and continue to yield molecules for new remedies. We analyzed studies published from 2009 to 2016 on the Annona species (Annonaceae), including A. coriacea, A. crassifolia, A. hypoglauca, A. muricata, A. squamosa, A. sylvatica, and A. vepretorum, as sources of potential antitumor agents. Here, we report and discuss the mechanisms of action and structure-activity relationships of the most active Annona constituents. Annonaceous acetogenins are one of the most promising classes of natural products, owing to their potential antitumor activity. However, their neurotoxicity should not be underestimated.

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“…A. muricata is used for curing hypertension, headaches, fever, rheumatism, diabetes, insomnia, parasite infection, diarrhea, dysentery and many more conditions [26,31]. Extract of A. muricata leaves is used as an alternative therapy for cancer as it causes apoptosis of the liver cancer cells [32]. Likewise, T. indica is used for abdominal pain, wound healing, constipation, inflammation, respiratory problems, diarrhea and dysentery [25,27,33].…”

Section: Introductionmentioning

confidence: 99%

Neglected and Underutilized Fruit Species in Sri Lanka: Prioritisation and Understanding the Potential Distribution under Climate Change

2019

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Neglected and underutilized fruit species (NUFS) can make an important contribution to the economy, food security and nutrition requirement for Sri Lanka. Identifying suitable areas for cultivation of NUFS is of paramount importance to deal with impending climate change issues. Nevertheless, limited studies have been carried out to assess the impact of climate change on the potential distribution of NUFS. Therefore, we examined the potential range changes of NUFS in a tropical climate using a case study from Sri Lanka. We prioritized and modeled the potentially suitable areas for four NUFS, namely Aegle marmelos, Annona muricata, Limonia acidissima and Tamarindus indica under current and projected climates (RCP 4.5 and RCP 8.5) for 2050 and 2070 using the maximum entropy (Maxent) species distribution modeling (SDM) approach. Potentially suitable areas for NUFS are predicted to decrease in the future under both scenarios. Out of the four NUFS, T. indica appears to be at the highest risk due to reduction in potential areas that are suitable for its growth under both emissions scenarios. The predicted suitable area reductions of this species for 2050 and 2070 are estimated as >75% compared to the current climate. A region of potentially higher climatic suitability was found around mid-county for multiple NUFS, which is also predicted to decrease under projected climate change. Further, the study identified high-potential agro-ecological regions (AERs) located in the mid-country’s wet and intermediate zones as the most suitable areas for promoting the cultivation of NUFS. The findings show the potential for incorporating predictive modeling into the management of NUFS under projected climate change. This study highlights the requirements of climate change adaptation strategies and focused research that can increase the resilience of NUFS to future changes in climate.

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Functional proteomic analysis revels that the ethanol extract of Annona muricata L. induces liver cancer cell apoptosis through endoplasmic reticulum stress pathway

Abstract: Our results indicate that the ethanol extract of leaves of Annona muricata L. causes apoptosis of liver cancer cells through ER stress pathway, which supports the ethnomedicinal use of this herb as an alternative or complementary therapy for cancer.

Cited by 61 publications

References 26 publications

MiR-410 Acts as a Tumor Suppressor in Estrogen Receptor-Positive Breast Cancer Cells by Directly Targeting ERLIN2 via the ERS Pathway

MiR-410 Acts as a Tumor Suppressor in Estrogen Receptor-Positive Breast Cancer Cells by Directly Targeting ERLIN2 via the ERS Pathway

Annona species (Annonaceae): a rich source of potential antitumor agents?

Neglected and Underutilized Fruit Species in Sri Lanka: Prioritisation and Understanding the Potential Distribution under Climate Change

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