Hesperidin Induces Paraptosis Like Cell Death in Hepatoblatoma, HepG2 Cells: Involvement of ERK1/2 MAPK

Yumnam, Silvia; Park, Ki-Soo; Kim, Mun Ki; Nagappan, Arulkumar; Hong, Gyeong Eun; Lee, Ho Jeong; Lee, Won Sup; Kim, Eun Hee; Cho, Jae Hyeon; Shin, Sung Chul; Kim, Gon Sup

doi:10.1371/journal.pone.0101321

Cited by 68 publications

(59 citation statements)

References 41 publications

(58 reference statements)

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“…Paraptosis is a form of programmed cell death described in pathologies like neurodegeneration ) that can also be induced by drugs used to treat cancer Ram & Ramakrishna 2014;Yumnam et al 2014;Zhang et al 2015). Our results reveal that follicular atresia is a complex system in which high levels of cell elimination are normal events.…”

Section: Discussionmentioning

confidence: 70%

Paraptosis‐like cell death in Wistar rat granulosa cells

et al. 2016

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Follicular atresia, a common process present in all mammals, involves apoptotic and autophagic cell death. However, the participation of paraptosis, a type of caspase-independent cell death, during follicular atresia is unknown. This study found swollen endoplasmic reticulum in the granulosa cells of adult Wistar rats. Calnexin was used as a marker of the endoplasmic reticulum at the ultrastructural and optical levels. The cells with swelling of the endoplasmic reticulum were negative to the TUNEL assay and active caspase-3 immunodetection, indicating that this swelling is not part of any apoptotic or autophagic process. Additionally, immunodetection of the CHOP protein was used as a marker of endoplasmic reticulum stress, and this confirmed the presence of the paraptosis process. These data suggest that paraptosis-like cell death is associated with the death of granulosa cells during follicular atresia in adult Wistar rats.

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Section: Discussionmentioning

confidence: 70%

Paraptosis‐like cell death in Wistar rat granulosa cells

et al. 2016

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“…Similarly, Saiprasad et al [35] showed that hesperidin can induce apoptosis through modulating BCL2/BAX levels to increase the activity of caspase-3 and caspase-9 in experimental colon cancer models. Furthermore, it has been found that hesperidin can induce cell death in hepatocellular carcinoma HepG2 cells in a caspase-independent manner by activating the ERK1/2 pathway [36]. Taken together, these results indicate that hesperidin may induce different cell death programs in different cancer cell types.…”

Section: Discussionmentioning

confidence: 77%

Anti-proliferative, apoptotic and signal transduction effects of hesperidin in non-small cell lung cancer cells

et al. 2015

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Purpose Hesperidin, a glycoside flavonoid, is thought to act as an anti-cancer agent, since it has been found to exhibit both pro-apoptotic and anti-proliferative effects in several cancer cell types. The mechanisms underlying hesperidin-induced growth arrest and apoptosis are, however, not well understood. Here, we aimed to investigate the anti-proliferative and apoptotic effects of hesperidin on non-small cell lung cancer (NSCLC) cells and to investigate the mechanisms involved. Methods The anti-proliferative and apoptotic effects of hesperidin on two NSCLC-derived cell lines, A549 and NCI-H358, were determined using a WST-1 colorimetric assay, a LDH cytotoxicity assay, a Cell Death Detection assay, an AnnexinV-FITC assay, a caspase-3 assay and a JC-1 assay, respectively, all in a time-and dose-dependent manner. As a control, non-cancerous MRC-5 lung fibroblasts were included. Changes in whole genome gene expression profiles were assessed using an Illumina Human HT-12v4 beadchip microarray platform, and subsequent data analyses were performed using an Illumina Genome Studio and Ingenuity Pathway Analyser (IPA). Results We found that after hesperidin treatment, A549 and NCI-H358 cells exhibited decreasing cell proliferation and increasing caspase-3 and other apoptosis-related activities, in conjunction with decreasing mitochondrial membrane potential activities, in a dose-and time-dependent manner. Through a GO analysis, by which changes in gene expression profiles were compared, we found that the FGF and NF-κB signal transduction pathways were most significantly affected in the hesperidin treated NCI-H358 and A549 NSCLC cells. Conclusions Our results indicate that hesperidin elicits an in vitro growth inhibitory effect on NSCLC cells by modulating immune response-related pathways that affect apoptosis. When confirmed in vivo, hesperidin may serve as a novel antiproliferative agent for non-small cell lung cancer.

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“…In HepG2 hepatocarcinoma cells, its ability to induce apoptosis via both mitochondrial and death receptor pathways has been demonstrated [153], as well as the non-apoptotic programmed cell death namely paraptosis [154]. Hesperidin also inhibits proliferation of Ramos Burkitt’s lymphoma cells and sensitizes them to doxorubicin-induced apoptosis through the inhibition of both constitutive and doxorubicin-mediated NF-κB activation in a PPARγ-independent manner [155].…”

Section: Preclinical Studiesmentioning

confidence: 99%

Chemopreventive Agents and Inhibitors of Cancer Hallmarks: May Citrus Offer New Perspectives?

et al. 2016

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Fruits and vegetables have long been recognized as potentially important in the prevention of cancer risk. Thus, scientific interest in nutrition and cancer has grown over time, as shown by increasing number of experimental studies about the relationship between diet and cancer development. This review attempts to provide an insight into the anti-cancer effects of Citrus fruits, with a focus on their bioactive compounds, elucidating the main cellular and molecular mechanisms through which they may protect against cancer. Scientific literature was selected for this review with the aim of collecting the relevant experimental evidence for the anti-cancer effects of Citrus fruits and their flavonoids. The findings discussed in this review strongly support their potential as anti-cancer agents, and may represent a scientific basis to develop nutraceuticals, food supplements, or complementary and alternative drugs in a context of a multi-target pharmacological strategy in the oncology.

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Hesperidin Induces Paraptosis Like Cell Death in Hepatoblatoma, HepG2 Cells: Involvement of ERK1/2 MAPK

Cited by 68 publications

References 41 publications

Paraptosis‐like cell death in Wistar rat granulosa cells

Paraptosis‐like cell death in Wistar rat granulosa cells

Anti-proliferative, apoptotic and signal transduction effects of hesperidin in non-small cell lung cancer cells

Chemopreventive Agents and Inhibitors of Cancer Hallmarks: May Citrus Offer New Perspectives?

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