Hesperidin induces apoptosis and triggers autophagic markers through inhibition of Aurora-A mediated phosphoinositide-3-kinase/Akt/mammalian target of rapamycin and glycogen synthase kinase-3 beta signalling cascades in experimental colon carcinogenesis

Gowrikumar, Saiprasad; Palanivel, Chitra; Manikandan, R.; Sudhandiran, Ganapasam

doi:10.1016/j.ejca.2014.06.013

Cited by 101 publications

(63 citation statements)

References 46 publications

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“…Wang et al (32) identified that hesperidin inhibits HeLa cell viability by increasing cytochrome c protein. Additionally, Saiprasad et al (38) demonstrated that hesperidin induces apoptosis in colon carcinogenesis via the phosphoinositide 3-kinase/protein kinase B/glycogen synthase kinase-3β and cytochrome c signaling pathways (38). The results of the present study identified that hesperidin induces cytochrome c protein expression in ovarian cancer cells.…”

Section: Discussionsupporting

confidence: 60%

Hesperidin inhibits ovarian cancer cell viability through endoplasmic reticulum stress signaling pathways

Zhao

Gao

et al. 2017

Oncol Lett

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Abstract. Hesperidin is a vitamin P flavonoid compound primarily present in citrus fruits. The aim of the present study was to investigate whether hesperidin inhibits ovarian cancer cell viability via endoplasmic reticulum stress signaling pathways. A2780 cells were treated with various doses of hesperidin for 6, 12 or 24 h, and the viability of A2780 cells was assessed using the MTT assay. Hesperidin decreased the viability of A2780 cells and increased cytotoxicity in a doseand time-dependent manner. In addition, hesperidin induced apoptosis and increased cleaved caspase-3 protein expression levels in A2780 cells. Furthermore, hesperidin markedly increased the protein expression of anti-growth arrest-and DNA damage-inducible gene 153, anti-CCAAT'enhancer-binding protein homologous protein, glucose-regulated protein 78 and cytochrome c in A2780 cells. The results of the present study indicated that hesperidin inhibits cell viability and induces apoptosis in ovarian cancer cells via endoplasmic reticulum stress signaling pathways. Thus, hesperidin may offer a novel therapeutic tool for ovarian carcinoma.

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Section: Discussionsupporting

confidence: 60%

Hesperidin inhibits ovarian cancer cell viability through endoplasmic reticulum stress signaling pathways

Zhao

Gao

et al. 2017

Oncol Lett

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“…These results suggest that hesperidin may induce apoptosis in human colon cancer cells through caspase-3 activation [29]. 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].…”

Section: Discussionmentioning

confidence: 90%

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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“…Further, hesperidin administration stimulated autophagic markers like Beclin-1 and LC3-II by inhibiting mTOR protein (mammalian target of rapamycin), which is a key player in autophagy mediated cell death, Additionally hesperidin prevent the accumulation of ␤-catenin in cytoplasm by promoting the activity of glycogen synthase kinase-3 beta (GSK-3␤). Overall authors concluded that hesperidin plays major role in AOM mediated colon carcinogenicity by blocking the Aurora-A mediated PI3K/Akt/GSK-3␤ and mTOR signaling pathways by stimulating apoptosis and autophagy mediated cell death in mice (Saiprasad et al, 2014).…”

Section: Hesperidin Induced Apoptotic Cell Death In Colon Cancermentioning

confidence: 98%

Hesperidin: A promising anticancer agent from nature

Devi

Rajavel

Nabavi

et al. 2015

Industrial Crops and Products

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Hesperidin induces apoptosis and triggers autophagic markers through inhibition of Aurora-A mediated phosphoinositide-3-kinase/Akt/mammalian target of rapamycin and glycogen synthase kinase-3 beta signalling cascades in experimental colon carcinogenesis

Cited by 101 publications

References 46 publications

Hesperidin inhibits ovarian cancer cell viability through endoplasmic reticulum stress signaling pathways

Hesperidin inhibits ovarian cancer cell viability through endoplasmic reticulum stress signaling pathways

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

Hesperidin: A promising anticancer agent from nature

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