Combination treatment with platycodin D and osthole inhibits cell proliferation and invasion in mammary carcinoma cell lines

Ye, Yiyi; Han, Xin; Guo, Baofeng; Sun, Zhijing; Liu, Sheng

doi:10.1016/j.etap.2013.03.012

Cited by 31 publications

(26 citation statements)

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“…Amounts of studies showed that Osthole regulates cell apoptosis, proliferation and invasion via multiple signaling pathways in many cancer cells [13,15,16]. In addition, it has been reported in recent studies that Osthole has essential roles in brain functions by protecting neurons [17,18,19,20,21], suggesting that Osthole could penetrate the blood-brain barrier for the chemotherapy drugs of brain tumours.…”

Section: Discussionmentioning

confidence: 99%

Osthole Exhibits Anti-Cancer Property in Rat Glioma Cells Through Inhibiting PI3K/Akt and MAPK Signaling Pathways

Ding

Wei

Song

et al. 2013

Cell Physiol Biochem

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Aims: The purpose of this study was to investigate how Osthole affects glioma cell proliferation, apoptosis, invasion and migration. Methods: Rat glioma cells were treated with different concentrations of Osthole (0 µM, 25 µM, 50 µM, and 100 µM). Cell proliferation was assessed by measuring PCNA expression and CCK8 assay at different time points. Apoptosis was evaluated by measuring the expression of pro-apoptotic protein including Bax, Bcl2, PARP, and cleaved Caspase3, and of anti-apoptotic protein Survivin. Cell migration and invasion were assessed using different methods. Signaling pathways such as PI3K/Akt and MAPK, which are involved in the development of glioma cells, were also investigated in this study. Results: Treatment with Osthole markedly inhibits glioma cell proliferation, as assessed by western blot with the PCNA antibody. Osthole also induces cell apoptosis by upregulating the expression of pro-apoptotic proteins, and by reducing the expression of anti-apoptotic factors. Moreover, C6 cell migration and invasion were efficiently inhibited in groups treated with Osthole, compared to the control group. Additionally, inhibition of PI3K/Akt and MAPK signaling pathway was also observed in C6 cells treated with Osthole. Conclusions: Our findings showed an anti-cancer effect of Osthole on glioma cells, including the proliferation inhibition, apoptosis induction, and migration/invasion inhibition. Further investigation in C6 glioma cells implicated the role of Osthole in essential pathways controlling glioma cell progression. Taken together, our data suggested that Osthole may have a potential application in glioma therapy.

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Section: Discussionmentioning

confidence: 99%

Osthole Exhibits Anti-Cancer Property in Rat Glioma Cells Through Inhibiting PI3K/Akt and MAPK Signaling Pathways

Ding

Wei

Song

et al. 2013

Cell Physiol Biochem

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“…It was also found to enhance the anti-proliferative effects of doxorubicin in MCF-7 and MDA-MB-231 breast cancer cells (25). The combination of PD and osthole inhibited the proliferation and invasion of MDA-MB-231 and 4T1 human breast cancer cells (17). We performed the present studies to better understand the potential mechanisms by which PD decreases the viability of MDA-MB-231 cells.…”

Section: Discussionmentioning

confidence: 99%

“…As the most abundant triterpenoid saponin derived from the roots of Platycodin grandiflorum, Platycodin D (PD), has been reported to show a wide range of health benefits, such as anti-atherosclerotic (4), anti-inflammatory (5,6), hypocholesterolemic and anti-obesity effects (7). Previous studies have shown that PD has obvious anticancer activity against different human malignant cancer cells both in vitro (10,11,13,14,16,17) and in vivo (9,12,15).…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Among the various health benefits of PD, anticancer effects have been noted in several cancer cell lines, including lung cancer cells (9), hepatocellular carcinoma cells (10), gastric cancer cells (11), prostate cancer cells (12), and leukemia cells (13,14). PD has also been reported to inhibit the viability of human breast cancer cells in vitro (15)(16)(17).The mouse double minute-2 (mdm2) gene, which was discovered as an oncogene in 1991 (18), has been reported to be amplified in more than 40 different types of malignancies. As reported by Rayburn et al (19), the protein encoded by mdm2, MDM2, is associated with cancer development, progression, the resistance to chemotherapy, and can serve Platycodin D, a metabolite of Platycodin grandiflorum, inhibits highly metastatic MDA-MB-231 breast cancer growth in vitro and in vivo by targeting the MDM2 oncogene…”

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Platycodin D, a metabolite of Platycodin grandiflorum, inhibits highly metastatic MDA-MB-231 breast cancer growth in vitro and in vivo by targeting the MDM2 oncogene

Kong

Wang

et al. 2016

Oncology Reports

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Abstract. The objective of the present study was to explore the in vitro and in vivo anticancer effects of Platycodin D (PD), derived from Platycodin grandiflorum, on highly metastatic MDA-MB-231 breast cancer cells. Using the MTT assay, we found that PD inhibited MDA-MB-231 cell growth in a concentration-dependent manner, with an IC 50 value of 7.77±1.86 µM. Further studies showed that PD had antiproliferative effects and induced cell cycle arrest in the G0/G1 phase. To explore the detailed mechanism(s) by which PD suppressed MDA-MB-231 cell growth, western blot analyses were used to detect the expression levels of proteins related to cell proliferation and survival. The data showed that PD decreased the expression of proteins related to the G0/G1 phases, downregulated the protein expression of MDM2, MDMX, and mutant p53, and increased the expression levels of p21 and p27 in vitro. We verified the effects of PD on the expression of MDM2, MDMX, mutant p53, p21 and p27 using a pcDNA3-Flag-MDM2 plasmid and MDM2 siRNA transfection, and found that PD inhibited MDA-MB-231 cell viability by targeting MDM2 and mutant p53. Compared with the corresponding parental cells, the cells with siRNA-MDM2 transfection had a greater decrease in cell viability and proliferation, while those with pcDNA3-MDM2 plasmid transfection did not show any increase in the effects of PD. We also established a MDA-MB-231 xenograft model in BALB/c nude mice, and found that PD significantly inhibited the growth of MDA-MB-231 xenograft tumors in these mice. The expression levels of various proteins in the tumor tissue exhibited changes similar to those observed in vitro. These findings indicate that PD exerted in vitro and in vivo anticancer effects against MDA-MB-231 breast cancer cells, that PD is a potential MDM2/MDMX inhibitor, and that the anticancer effects of PD were likely associated with its inhibition of these proteins. Our observations help to identify a mechanism by which PD functions as an anti-breast cancer agent. IntroductionBreast cancer is the most frequently diagnosed malignancy and the leading cause of cancer death among females worldwide, accounting for 25% of all cancer cases and 15% of the total cancer deaths in 2012 (1). According to the American Cancer Society, about 231,840 new cases of invasive breast cancer and approximately 60,290 new cases of carcinoma in situ would occur in the US in 2015 (2). To relieve the huge burden of cancer therapy and promote women's health, there is an urgent need to discover new drugs to treat breast cancer.Natural products, such as thymoquinone, wogonin, naphtho, and quercetin, have been shown to possess different anticancer functions, such as the induction of cell cycle arrest, suppression of tumor angiogenesis, and inhibition of cell migration or invasion (3). Platycodin D (PD), a triterpenoid saponin derived from the roots of Platycodin grandiflorum, has been reported to possess a wide rangeof health benefits, such as anti-atherosclerotic (4), anti-inflammatory (5,6), hypocholesterolemic, ...

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TGFβ modulates inflammatory cytokines and growth factors to create premetastatic microenvironment and stimulate lung metastasis

Liu

et al. 2015

J Mol Hist

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The formation of tumor-promoting premetastatic microenvironment plays a pivotal role on metastatic progression. Understanding how the primary tumor can promote the formation of premetastatic microenvironment in the lung will aid discovery of a final cure for metastatic breast cancer. The murine 4T1 mammary carcinoma cells were injected into the mammary fat pads of the BALB/c mice. Days 0-14 were considered the premetastatic phase. Lung tissues were examined using hematoxylin-eosin staining and transmission electron microscopy. After intravenous injection of TGFβ1 pretreated 4T1 cells, the relative pulmonary vascular permeability was quantified, the extravasation, survival, and proliferation of tumor cells in premetastatic lungs were evaluated, and the levels of S100A8, S100A9, VEGF, and Angpt2 were detected in tumor-bearing mice. The results showed that during the premetastatic phase, an inflammatory response and inflammation-induced vascular hyperpermeability were established, leading to an abnormal pulmonary microenvironment, which facilitated extravasation of circulating tumor cells, and subsequent survival and proliferation of metastatic tumor cells in a TGFβ-dependent manner. Moreover, the expressions of S100A8, S100A9, VEGF, and Angpt2 were increased, and an induction of these genes by TGFβ was further observed in premetastatic lungs. Thus, this study demonstrated that TGFβ promoted the creation of premetastatic microenvironment by modulating certain crucial inflammatory cytokines and growth factors, and finally enhanced the ability of circulating cells to seed the lung.

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Combination treatment with platycodin D and osthole inhibits cell proliferation and invasion in mammary carcinoma cell lines

Cited by 31 publications

References 31 publications

Osthole Exhibits Anti-Cancer Property in Rat Glioma Cells Through Inhibiting PI3K/Akt and MAPK Signaling Pathways

Osthole Exhibits Anti-Cancer Property in Rat Glioma Cells Through Inhibiting PI3K/Akt and MAPK Signaling Pathways

Platycodin D, a metabolite of Platycodin grandiflorum, inhibits highly metastatic MDA-MB-231 breast cancer growth in vitro and in vivo by targeting the MDM2 oncogene

TGFβ modulates inflammatory cytokines and growth factors to create premetastatic microenvironment and stimulate lung metastasis

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