SB365, Pulsatilla saponin D suppresses the proliferation of human colon cancer cells and induces apoptosis by modulating the AKT/mTOR signalling pathway

Son, Mi Kwon; Jung, Kyung Hee; Hong, Sang–Won; Lee, Hee-Seung; Zheng, Hongmei; Choi, Myung‐Joo; Seo, Ju Hyeon; Suh, Jun‐Kyu; Hong, Soon‐Sun

doi:10.1016/j.foodchem.2012.07.096

Cited by 45 publications

(36 citation statements)

References 36 publications

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“…Akt/mTOR pathway activation is downstream accompanied with signals promoting resistance to apoptosis, altered tissue remodeling and metastasis formation (Guertin and Sabatini, 2007). In particular, following Akt/mTOR/p70S6K axis induction, HIF-1α expression is observed (Liu et al, 2006;Shaw and Cantley, 2006;Zhou et al, 2007), and this protein directly enhances VEGF secretion that, in turn, acts as a powerful proangiogenic effector in colon epithelial cells and strongly promotes colon carcinoma progression (Son et al, 2013). VEGF binding at VEGF-R2 is downstream followed by a complex molecular network, including ERK, JNK, PI3K, Akt, P70S6K and p38MAPK that subsequently promote proliferation, migration and tube formation of endothelial cells (Ferrara et al, 2003), converging to massive neovascularization.…”

Section: Discussionmentioning

confidence: 99%

Palmitoylethanolamide Exerts Antiproliferative Effect and Downregulates VEGF Signaling in Caco-2 Human Colon Carcinoma Cell Line Through a Selective PPAR-α-Dependent Inhibition of Akt/mTOR Pathway

et al. 2016

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Palmitoylethanolamide (PEA) is a nutraceutical compound that has been demonstrated to improve intestinal inflammation. We aimed at evaluating its antiproliferative and antiangiogenic effects in human colon adenocarcinoma Caco-2 cell line. Caco-2 cells were treated with increasing concentrations of PEA (0.001, 0.01 and 0.1 μM) in the presence of peroxisome proliferator-activated receptor-a (PPAR-α) or PPAR-γ antagonists. Cell proliferation was evaluated by performing a MTT assay. Vascular endothelial growth factor (VEGF) release was estimated by ELISA, while the expression of VEGF receptor and the activation of the Akt/mammalian target of rapamycin (mTOR) pathway were evaluated by western blot analysis. PEA caused a significant and concentration-dependent decrease of Caco-2 cell proliferation at 48 h. PEA administration significantly reduced in a concentration-dependent manner VEGF secretion and VEGF receptor expression. Inhibition of Akt phosphorylation and a downstream decrease of phospho-mTOR and of p-p70S6K were observed as compared with untreated cells. PPAR-α, but not PPAR-γ antagonist, reverted all effects of PEA. PEA is able to decrease cell proliferation and angiogenesis. The antiangiogenic effect of PEA depends on the specific inhibition of the AkT/mTOR axis, through the activation of PPAR-α pathway. If supported by in vivo models, our data pave the way to PEA co-administration to the current chemotherapeutic regimens for colon carcinoma. Copyright © 2016 John Wiley & Sons, Ltd.

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Section: Discussionmentioning

confidence: 99%

Palmitoylethanolamide Exerts Antiproliferative Effect and Downregulates VEGF Signaling in Caco-2 Human Colon Carcinoma Cell Line Through a Selective PPAR-α-Dependent Inhibition of Akt/mTOR Pathway

et al. 2016

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“…chinensis ): The Pulsatilla genus has been historically used in both Korean and Chinese medicinal applications in the treatment of dysentery, malaria, and bacterial infections. A number of studies are now showing that the extracts of Pulsatilla contain saponins isolated from the root, in part capable of suppressing growth of diverse tumor cells including anaplastic thyroid (Park et al ., ), colon and hepatocellular carcinoma by inducing apoptosis, initiating reduction of vascular endothelial growth factor (Park, Jung, 2012) and suppression of the AKT/mTOR pathway (Son et al ., ) (Hong et al ., ). Several saponins isolated from Pulsatilla koreana root are toxic to diverse cancer cell lines, such as A‐549, SK‐OV‐3, SK‐MEL‐2, HCT15, human liver 7402 cells (Xu et al ., ), effective against BDF1 mice bearing Lewis lung carcinoma (Bang et al ., ; Kim et al ., ), and tumor growth in xenograft models (Hong et al ., ).…”

Section: Discussionmentioning

confidence: 99%

High Throughput Screening of Natural Products for Anti‐mitotic Effects in MDA‐MB‐231 Human Breast Carcinoma Cells

Mazzio

Badisa

Mack

et al. 2013

Phytotherapy Research

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Some of the most effective anti-mitotic microtubule-binding agents, such as paclitaxel (Taxus brevifolia) were originally discovered through robust NCI botanical screenings. In this study, a high-through microarray format was utilized to screen 897 aqueous extracts of commonly used natural products (0.00015–0.5 mg/ml) relative to paclitaxel for anti-mitotic effects (independent of toxicity) on proliferation of MDA-MB-231 cells. The data obtained showed that less than 1.34 % tested showed inhibitory growth (IG50) properties <0.0183 mg/ml. The most potent anti-mitotics (independent of toxicity) were Mandrake root (Podophyllum peltatum), Truja Twigs (Thuja occidentalis), Colorado desert mistletoe (Phoradendron flavescens), Tou Gu Cao Speranskia Herb (Speranskia tuberculata), Bentonite Clay, Bunge Root (Pulsatilla chinensis), Brucea Fruit (Brucea javanica), Madder Root (Rubia tinctorum), Gallnut of Chinese Sumac (Melaphis chinensis), Elecampane Root (Inula Helenium), Yuan Zhi Root (Polygala tenuifolia), Pagoda Tree Fruit (Melia Toosendan), Stone Root (Collinsonia Canadensis) and others such as American Witchhazel, Arjun and Bladderwrack. The strongest tumoricidal herbs identified from amongst the subset evaluated for anti-mitotic properties were wild yam (Dioscorea villosa), beth-root (Trillium Pendulum) and alkanet-root (Lithospermum canescens). Additional data was obtained on a lesser-recognized herb: (Speranskia tuberculata) which showed growth inhibition on BT-474 (human ductal breast carcinoma) and Ishikawa (human endometrial adenocarcinoma) cells with ability to block replicative DNA synthesis leading to G2 arrest in MDA-MB-231 cells. In conclusion, these findings present relative potency of natural anti-mitotic resources effective against human breast carcinoma MDA-MB-231 cell division.

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“…In particular, several triterpenoid saponins have been observed to exert higher sensitivity on cancer cells than normal cells, suggesting their potential safety as anticancer agents [6,15,28,38,44,45,53,67,74,81,86,91]. Furthermore, the anticancer activities of triterpenoid saponins have been evaluated in various animal models bearing human or animal cancers [18,21,33,34,41,42,54,56,58,60,[64][65][66][67]77,78,[80][81][82][89][90][91][92]97]. Of note, the tested triterpenoid saponins were generally very well tolerated in animals at doses that caused tumor regression, and showed no observable toxicity, such as injury of organs or changes in body weight.…”

Section: Triterpenoid Saponins In the Prevention And Therapy Of Cancersmentioning

confidence: 99%

Research Progress on Natural Triterpenoid Saponins in the Chemoprevention and Chemotherapy of Cancer

Long

Chen

2014

The Enzymes

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SB365, Pulsatilla saponin D suppresses the proliferation of human colon cancer cells and induces apoptosis by modulating the AKT/mTOR signalling pathway

Cited by 45 publications

References 36 publications

Palmitoylethanolamide Exerts Antiproliferative Effect and Downregulates VEGF Signaling in Caco-2 Human Colon Carcinoma Cell Line Through a Selective PPAR-α-Dependent Inhibition of Akt/mTOR Pathway

Palmitoylethanolamide Exerts Antiproliferative Effect and Downregulates VEGF Signaling in Caco-2 Human Colon Carcinoma Cell Line Through a Selective PPAR-α-Dependent Inhibition of Akt/mTOR Pathway

High Throughput Screening of Natural Products for Anti‐mitotic Effects in MDA‐MB‐231 Human Breast Carcinoma Cells

Research Progress on Natural Triterpenoid Saponins in the Chemoprevention and Chemotherapy of Cancer

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