Sideroxylin (<i>Callistemon lanceolatus</i>) suppressed cell proliferation and increased apoptosis in ovarian cancer cells accompanied by mitochondrial dysfunction, the generation of reactive oxygen species, and an increase of lipid peroxidation

Lim, Whasun; Jeong, Wooyoung; Bazer, Fuller W.; Lee, Dong‐Ho; Song, Gwonhwa

doi:10.1002/jcp.26540

Cited by 18 publications

(14 citation statements)

References 29 publications

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“…Among the six LPA receptors, LPA1 receptor and LPA2 receptor are most extensively studied and their specific antagonists are widely used in research (Lee et al, 2019;Lopez-Serrano et al, 2019). It has been reported that LPA induces activation of the MAPK pathway, which consists of ERK1/2, p38, and JNK (Park et al, 2018). Here we investigated the molecular mechanisms underlying LPA-induced cell death.…”

Section: Introductionmentioning

confidence: 98%

Lysophosphatidic Acid Induces Apoptosis of PC12 Cells Through LPA1 Receptor/LPA2 Receptor/MAPK Signaling Pathway

Zhang

Wang

et al. 2020

Front. Mol. Neurosci.

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Lysophosphatidic acid is a small extracellular signaling molecule, which is elevated in pathological conditions such as ischemic stroke and traumatic brain injury (TBI). LPA regulates the survival of neurons in various diseases. However, the molecular mechanisms underlying LPA-induced neuronal death remain unclear. Here we report that LPA activates LPA1 and LPA2 receptors, and the downstream MAPK pathway to induce the apoptosis of PC12 cells through mitochondrial dysfunction. LPA elicits the activation of ERK1/2, p38, and JNK pathways, decreases the expression of Bcl2, promotes the translocation of Bax, and enhances the activation of caspase-3, resulting in mitochondrial dysfunction and cell apoptosis. This process can be blocked by LPA1 receptor antagonist and LPA2 receptor antagonist and MAPK pathway inhibitors. Our results indicate that LPA1 receptor, LPA2 receptor and MAPK pathway play a critical role in LPA-induced neuronal injury. LPA receptors and MAPK pathways may be novel therapeutic targets for ischemic stroke and TBI, where excessive LPA signaling exist.

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Section: Introductionmentioning

confidence: 98%

Lysophosphatidic Acid Induces Apoptosis of PC12 Cells Through LPA1 Receptor/LPA2 Receptor/MAPK Signaling Pathway

Zhang

Wang

et al. 2020

Front. Mol. Neurosci.

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“…The antiproliferative effects of sideroxylin against ovarian cancer cells are through the induction of mitochondrial dysfunction and the activation of PI3 K and MAPK signal transduction. 45 Selectivity Index (SI) of active compounds was determined in order to investigate, whether the cytotoxic activity was specific to cancer cells. The SI of the samples is defined as the ratio of cytotoxicity (IC50 values) on normal cells (Vero cells) to cancer cells: SI = IC 50 on Vero cells/IC50 on cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Potential anti-proliferative effects of chemical constituents and hemisynthetic derivatives from Scadoxus pseudocaulus (Amarillydaceae)

Pagning¹,

Tamokou²,

Muhammad³

et al. 2020

Afr H. Sci.

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Background: Biological significance of Amaryllidaceae is well advocated from the literature. In Cameroon, plants from this fam- ily are routinely used for the cure of liver, cancer and cardiovascular diseases. To date, no scientific investigation corresponding to the anti-cancer activity of extracts and isolated compounds of Scadoxus pseudocaulus is available. Objective: Current study is focused to elaborate the anti-proliferative effects of natural isolates (compounds 1-6, 9) and hemi-synthetic analogs (compounds 7-8) extracted from S. pseudocaulu. Methods: Column chromatography of the ethyl acetate extract followed by purification of different fractions led to the isolation of seven compounds (1 – 6, 9). Esterification reaction of compound 6 was carried out using butyroyl chlorides and triethylamin to produce two derivatives (7 – 8). The cytotoxic activity was performed after staining of treated cells with florescent dye propid- ium iodide. Dead cells were detected using cytometer FL2 or FL3 channels/filters. Results: Trans-derivative of narciclasine (a natural isolate from S. pseudocaulus), was found to be most potent among all tested compounds. Its effects were more significant on low malignant follicular lymphoma (DoHH2 cells) as compared to highly ma- lignant (EBV infected) Burkitts lymphoma (Raji cells). Conclusion: From our results, narciclasine appears to hold the potential of a lead molecule that can be used to bridge the ther- apeutic gaps in cancer research. Keywords: Scadoxus pseudocaulus; Amaryllidaceae; 7-deoxy-trans-dihydronarciclasin; farrerol; derivatization; cytotoxic activity.

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“…However, excessive production of ROS through external stimulation can lead to cancer cell death due to high levels of ROS in cancer cells compared to the ROS levels in normal cells [37]. We previously demonstrated that the induction of ROS production and lipid peroxidation by external stimuli is a mechanism to induce anticancer effects in EOC cells [38,39]. Furthermore, EOC cells are reported to protect themselves through well-organized mitochondrial biomass and are thereby resistant to chemotherapy [40].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of miR-214-3p Aids in Preventing Epithelial Ovarian Cancer Malignancy by Increasing the Expression of LHX6

Yang

Kim

Park

et al. 2019

Cancers

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In human epithelial ovarian cancer (EOC), various miRNAs can function as either oncogenes or tumor suppressor genes. We investigated miRNAs known to be involved in EOC progression and analyzed their expression in tissues and serum-derived exosomes from benign serous cystadenoma, borderline serous tumor, low-grade serous ovarian cancer, and high-grade serous ovarian cancer patients (HGSO). The HGSO group was divided based on the platinum-free interval, which is defined as the duration from the completion of platinum-based chemotherapy to recurrence. We also analyzed the mRNA levels of target genes that candidate miRNAs might regulate in patient tissues. miR-214-3p was highly expressed in tissues and exosomes derived from EOC with high malignancy and also found to regulate the expression of LIM homeobox domain 6 (LHX6) mRNA. Serum exosomal levels of miR-214-3p were significantly increased in platinum-resistant HGSO (25.2-fold, p < 0.001) compared to the exosomal expression of benign tumor patients. On transfection of miR-214-3p inhibitor in EOC cells, cell proliferation was inhibited while apoptotic cell death was increased. Collectively, we suggest that miR-214-3p in serum exosomes can be a potential biomarker for the diagnosis and prognosis of ovarian tumor, and its inhibition can be a supportive treatment for EOC.

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Sideroxylin (Callistemon lanceolatus) suppressed cell proliferation and increased apoptosis in ovarian cancer cells accompanied by mitochondrial dysfunction, the generation of reactive oxygen species, and an increase of lipid peroxidation

Cited by 18 publications

References 29 publications

Lysophosphatidic Acid Induces Apoptosis of PC12 Cells Through LPA1 Receptor/LPA2 Receptor/MAPK Signaling Pathway

Lysophosphatidic Acid Induces Apoptosis of PC12 Cells Through LPA1 Receptor/LPA2 Receptor/MAPK Signaling Pathway

Potential anti-proliferative effects of chemical constituents and hemisynthetic derivatives from Scadoxus pseudocaulus (Amarillydaceae)

Inhibition of miR-214-3p Aids in Preventing Epithelial Ovarian Cancer Malignancy by Increasing the Expression of LHX6

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