<i>Anemarrhena asphodeloides</i> Bunge and its constituent timosaponin‐<scp>AIII</scp> induce cell cycle arrest and apoptosis in pancreatic cancer cells

MarElia, Catherine B.; Sharp, Arielle; Shemwell, Tiffany A.; Zhang, Y. Clare; Burkhardt, Brant R.

doi:10.1002/2211-5463.12457

Cited by 25 publications

(17 citation statements)

References 29 publications

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“…Moreover, Timo AIII selectively induces cell death in tumor cells but not in normal cells and has been suggested to be a novel potential anticancer compound in recent years [ 14 , 15 ]. Timo AIII presents antitumor activity in various cancers, such as non-small cell lung cancer [ 16 ], pancreatic cancer [ 17 ], melanoma [ 18 , 19 ], breast cancer [ 20 ], hepatocellular carcinoma [ 21 ], colon cancer [ 22 ], promyelocytic leukemia [ 23 ] and so on. In addition, Chen et al found that Timo AIII also reverses multidrug resistance in human chronic myelogenous leukemia [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Antiangiogenesis effect of timosaponin AIII on HUVECs in vitro and zebrafish embryos in vivo

et al. 2019

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Timosaponin AIII (Timo AIII) is a natural steroidal saponin isolated from the traditional Chinese herb Anemarrhena asphodeloides Bge with proved effectiveness in the treatment of numerous cancers. However, whether Timo AIII suppresses tumor angiogenesis remains unclear. In the present study, we investigated the antiangiogenesis effects of Timo AIII and the underlying mechanisms in human umbilical vein endothelial cells (HUVECs) in vitro and zebrafish embryos in vivo. We showed that treatment with Timo AIII (0.5–2 µM) partially disrupted the intersegmental vessels (ISVs) and subintestinal vessels (SIVs) growth in transgenic zebrafish Tg( fli-1a : EGFP) y1 . Timo AIII (0.5–4 µM) dose-dependently inhibited VEGF-induced proliferation, migration, invasion, and tube formation of HUVECs, but these inhibitory effects were not due to its cytotoxicity. We further demonstrated that Timo AIII treatment significantly suppressed the expression of VEGF receptor (VEGFR) and the phosphorylation of Akt, MEK1/2, and ERK1/2 in HUVECs. Timo AIII treatment also significantly inhibited VEGF-triggered phosphorylation of VEGFR2, Akt, and ERK1/2 in HUVECs. Moreover, we conducted RNA-Seq and analyzed the transcriptome changes in both HUVECs and zebrafish embryos following Timo AIII treatment. The coexpression network analysis results showed that various biological processes and signaling pathways were enriched including angiogenesis, cell motility, cell adhesion, protein serine/threonine kinase activity, transmembrane signaling receptor activity, growth factor activity, etc., which was consistent with the antiangiogenesis effects of Timo AIII in HUVECs and zebrafish embryos. We conclude that the antiangiogenesis effect of Timo AIII is mediated through VEGF/PI3K/Akt/MAPK signaling cascade; Timo AIII potentially exerts antiangiogenesis effect in cancer treatment.

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Section: Introductionmentioning

confidence: 99%

Antiangiogenesis effect of timosaponin AIII on HUVECs in vitro and zebrafish embryos in vivo

et al. 2019

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“…Taken together, these results reveal that TSAIII increases miR-129-5p, which subsequently binds to the 3′-UTR of CTSC gene and suppresses the protein expression of CTSC, and consequently inhibits the migration and invasion of RCC cells. The proposed mechanism that TSAIII inhibits migration and invasion of RCC cells is presented inFigure 8.4 | DISCUSSIONSIt has been reported that TSAIII exerts anticancer activities through various mechanisms, such as induction of apoptosis, autophagy, and cell cycle arrest for BxPC-3, HepG2, and A375-S2 cells(MarElia et al, 2018;Nho, Chun, & Kim, 2016;Wang et al, 2017).Recently, Jung et al, (2016) also reported that TSAIII can inhibit the migration and invasion of A549 cells via ERK/Src/FAK-mediated MMP expression.…”

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confidence: 99%

Timosaponin AIII inhibits metastasis of renal carcinoma cells through suppressing cathepsin C expression by AKT/miR‐129‐5p axis

Chiang

Lai

Chiou

et al. 2019

Journal Cellular Physiology

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Timosaponin AIII (TSAIII) is a steroidal saponin that exerts anticancer activity on various cancer cells. In this study, we explore the effects of TSAIII on renal cell carcinoma (RCC) cells. Our findings show that TSAIII treatment (<8 μM) insignificantly influenced cell viability and cell cycle distribution of human RCC cell lines 786‐O, A‐498, and ACHN. Further observations revealed that TSAIII inhibited migration and invasion of 786‐O and A‐498 cells, as well as significantly decreased the production and expression of cathepsin C (CTSC) in both the cell types. Kinase cascade analysis exhibited that PI3K/AKT activation was inhibited, but PTEN expression was increased, in response to TSAIII treatments. Combining TSAIII and PI3K inhibitors, LY294002 synergically reduced the migration and invasion of 786‐O and A‐498 cells, as well as decreased the CTSC expression in both the cell types. We also observed that miR‐129‐5p bound to CTSC gene and suppressed the expression of CTSC and demonstrated that the miR‐129‐5p expression was synergically enhanced by TSAIII and LY294002. In addition, pretreatment with antago‐miR‐129‐5p significantly restored the CTSC expression and the migration and invasion of TSAIII‐treated 786‐O cells. In conclusion, our findings reveal that TSAIII inhibits the metastatic properties of RCC cells, contributing to the inhibition of PI3K/AKT and the increase of miR‐129‐5p and the subsequent downregulation of CTSC. This suggests that TSAIII has significant antimetastatic activity against RCC cells and may be beneficial to RCC treatments.

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“…Thus, mitochondria are at least one of the target structures that suffer from excessive doses and prolonged exposition to A. asphodeloides xanthone fraction. This phenomenon could be also exploited for further anticancer studies as it has been already demonstrated for other constituents from A. asphodeloides rhizoma, i.e., timosaponin A-III and other triterpenoids [34,35].…”

Section: Discussionmentioning

confidence: 69%

Anemarrhenae asphodeloides rhizoma Extract Enriched in Mangiferin Protects PC12 Cells against a Neurotoxic Agent-3-Nitropropionic Acid

Piwowar

Rembiałkowska

Rorbach-Dolata

et al. 2020

IJMS

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The rhizome of Anemarrhena asphodeloides Bunge, used in Traditional Chinese Medicine as a brain function-improving herb, is a promising source of neuroprotective substances. The aim of this study was to evaluate the protective action of xanthones from A. asphodeloides rhizomes on the PC12 cell line exposed to the neurotoxic agent—3-nitropropionic acid (3-NP). The xanthone-enriched fraction of the ethanolic extract of A. asphodeloides (abbreviated from now on as XF, for the Xanthone Fraction), rich in polyphenolic xanthone glycosides, in concentrations from 5 to 100 μg/mL, and 3-NP in concentrations from 2.5 to 15 mM, were examined. After 8, 16, 24, 48, and 72 h of exposure of cells to various combinations of 3-NP and XF, the MTT viability assay was performed and morphological changes were estimated by confocal fluorescence microscopy. The obtained results showed a significant increase in the number of cells surviving after treatment with XF with exposure to neurotoxic 3-NP and decreased morphological changes in PC12 cells in a dose and time dependent manner. The most effective protective action was observed when PC12 cells were pre-incubated with the XF. This effect may contribute to the traditional indications of this herb for neurological and cognitive complaints. However, a significant cytotoxicity observed at higher XF concentrations (over 10 µg/mL) and longer incubation time (48 h) requires caution in future research and thorough investigation into potential adverse effects.

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Anemarrhena asphodeloides Bunge and its constituent timosaponin‐AIII induce cell cycle arrest and apoptosis in pancreatic cancer cells

Cited by 25 publications

References 29 publications

Antiangiogenesis effect of timosaponin AIII on HUVECs in vitro and zebrafish embryos in vivo

Antiangiogenesis effect of timosaponin AIII on HUVECs in vitro and zebrafish embryos in vivo

Timosaponin AIII inhibits metastasis of renal carcinoma cells through suppressing cathepsin C expression by AKT/miR‐129‐5p axis

Anemarrhenae asphodeloides rhizoma Extract Enriched in Mangiferin Protects PC12 Cells against a Neurotoxic Agent-3-Nitropropionic Acid

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