[RETRACTED ARTICLE] Suppressive effect of platycodin D on bladder cancer through microRNA-129-5p-mediated PABPC1/PI3K/AKT axis inactivation

Chen, Dayin; Chen, Tingyu; Guo, Yingxue; Wang, Chennan; Dong, Longxin; Lu, Chunfeng

doi:10.1590/1414-431x202010222

Cited by 8 publications

(5 citation statements)

References 40 publications

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“…Ultimately, PI3K and its modulators may be attractive targets in cancer treatment, as they contribute to chemotherapeutic resistance, which induces cancer cell apoptosis (Mayer and Arteaga 2016;Lien et al 2017). Similar to the results of several previous studies Xu et al 2014;Zhao et al 2015;Seo et al 2018;Chen et al 2021), we also found that PD reduced the levels of phosphorylated PI3K, Akt, and mTOR, meaning that the PI3K/Akt/mTOR signaling was inactivated in PD-treated cells. Furthermore, an inhibitor of PI3K, LY294002, markedly increased the apoptotic potential of PD and further suppressed cell viability, supporting our conclusion that PD-induced EJ cell apoptosis was mediated by the inhibition of PI3K/Akt/mTOR signaling.…”

Section: Discussionsupporting

confidence: 90%

“…In this study, we also found that PD effectively induced apoptotic cell death in human bladder urothelial carcinoma cells. Importantly, the concentrations of PD used in the present experiments did not significantly affect the viability of normal cells (Khan et al 2016;Chen et al 2021), indicating that PD may selectively induce apoptosis in cancer cells. We demonstrated that PD activated caspase-9 as well as caspase-8, inhibited the expression of IAP-family proteins, and promoted mitochondrial dysfunction in EJ cells, accompanied by enhancement of the Bax/Bcl-2 expression ratio, cytoplasmic release of cytochrome c, and loss of MMP.…”

Section: Discussionmentioning

confidence: 65%

“…Previous studies also demonstrated that PD exhibited anti-proliferative effects by inducing cell cycle arrest and apoptosis in many types of cancer cells (Shin et al 2009;Chun and Kim 2012;Yu and Kim 2012;Xu et al 2014;Zhao et al 2015;Khan et al 2016;Seo et al 2018;Zhang et al 2020). Although Chen et al (2020Chen et al ( , 2021 recently reported that PD inhibited the proliferation of human bladder cancer cells through induction of apoptosis; the underlying mechanisms involved in apoptosis are still unclear. Therefore, in the present study, we investigated the effect of PD on apoptosis in human bladder urothelial carcinoma cells and identified the mechanism.…”

Section: Introductionmentioning

confidence: 99%

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Induction of apoptosis through inactivation of ROS-dependent PI3K/Akt signaling pathway by platycodin D in human bladder urothelial carcinoma cells

Park¹,

Cha²,

Lee³

et al. 2022

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Platycodin D (PD) is a triterpenoid saponin, a major bioactive constituent of the roots of Platycodon grandiflorum, which is well known for possessing various pharmacological properties. However, the anti-cancer mechanism of PD in bladder cancer cells remains poorly understood.In the current study, we investigated the effect of PD on the growth of human bladder urothelial carcinoma cells. PD treatment significantly reduced the cell survival of bladder cancer cells associated with induction of apoptosis and DNA damage. PD inhibited the expression of inhibitor of apoptosis family members, activated caspases, and induced cleavage of poly (ADP-ribose) polymerase. PD also increased the release of cytochrome c into the cytoplasm by disrupting the mitochondrial membrane potential while upregulating the expression ratio of Bax to Bcl-2. The PD-mediated anti-proliferative effect was significantly inhibited by pre-treatment with a pancaspase inhibitor, but not by an inhibitor of necroptosis. Moreover, PD suppressed the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway, and the apoptosis-inducing effect of PD was further enhanced by a PI3K inhibitor. In addition, PD increased the accumulation of reactive oxygen species (ROS), whereas N-acetyl cysteine (NAC), an ROS inhibitor, significantly attenuated the growth inhibition and inactivation of the PI3K/

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 99%

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Induction of apoptosis through inactivation of ROS-dependent PI3K/Akt signaling pathway by platycodin D in human bladder urothelial carcinoma cells

Park¹,

Cha²,

Lee³

et al. 2022

gpb

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“…PD is a triterpenoid saponin present in the roots of P. grandiflorum . Increasing evidence suggests that PD has a wide spectrum of antitumor activity, exhibiting significant growth inhibitory effects and strong cytotoxicity against various cancers ( 29 – 33 ). Our in vitro and in vivo experiments also showed that PD exerted an antitumor effect on KRAS -mutant CRC cells.…”

Section: Discussionmentioning

confidence: 99%

Platycodin D sensitizes KRAS-mutant colorectal cancer cells to cetuximab by inhibiting the PI3K/Akt signaling pathway

Liu

Song

et al. 2022

Front. Oncol.

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Cetuximab is a monoclonal antibody against epidermal growth factor receptor that blocks downstream signaling pathways of receptor tyrosine kinases, including Ras/Raf/MAPK and PI3K/Akt, thereby inhibiting tumor cell proliferation and inducing cancer cell apoptosis. Owing to KRAS mutations, the effectiveness of cetuximab is usually limited by intrinsic drug resistance. Continuous activation of the PI3K/Akt signaling pathway is another reason for cetuximab resistance. Platycodin-D, a bioactive compound isolated from the Chinese herb Platycodon grandiflorum, regulates Akt in different trends based on tissue types. To investigate whether platycodin-D can sensitize KRAS-mutant colorectal cancer cells to cetuximab by inhibiting the PI3K/Akt signaling pathway, HCT116 and LoVo cells were treated with cetuximab and platycodin-D. LY294002 and SC79 were used to regulate Akt to further evaluate whether platycodin-D sensitizes cells to cetuximab by inhibiting Akt. Our results confirmed that platycodin-D increased the cytotoxic effects of cetuximab, including inhibition of growth, migration, and invasion, via downregulation of PI3K and Akt phosphorylation in HCT116 and LoVo cells both in vitro and in vivo. Given these data, platycodin-D may sensitize KRAS-mutant colorectal cancer cells to cetuximab via inhibition of the PI3K/Akt signaling pathway.

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“…Several studies revealed that PD possesses various pharmacological properties due to its antioxidant [12][13][14], anti-inflammatory [15,16], hepatoprotective [17,18], anti-obesity [19,20], and immunological adjuvant activities [21]. In addition, some studies have described anticarcinogenic effects of PD against many types of cancers in vitro and in vivo [22,23]. For example, the concentration of 10~40 µM PD inhibited tumor invasion and metastasis in human oral squamous cell carcinoma, hepatocellular carcinoma, breast carcinoma cells via targeting multiple signaling pathways [24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Induction of ROS-dependent apoptotic cell death by platycodin D in human prostate cancer PC3 cells

Choi

2022

J. Mens. Health

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Background and objective: Platycodin D (PD), a triterpenoid saponin isolated from an edible and medicinal plant Platycodon grandiflorum, possesses multiple pharmacological properties. The purpose of this study is to investigate the effect of PD on the growth of PC3 human prostate cancer cells and the underlying molecular mechanisms. Materials and methods:Cell viability, apoptosis and mitochondrial membrane potential (MMP) were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, nuclear staining and flow cytometry analysis. To investigate the mechanism of anti-cancer activity of PD, expression of apoptosis regulatory protein, caspase activity, and generation of intracellular reactive oxygen species (ROS) were determined.Results: PD treatment reduced PC3 cell proliferation, which was associated with induction of apoptosis, and accompanied by increased expression of Fas, Fas-ligand (FasL) and pro-apoptotic Bax, and decreased expression of anti-apoptotic Bcl-2 and truncation of Bid. PD also inhibited expression of c-FLIP and members of inhibitor of apoptosis protein family, and activated caspases, resulting in an increase in poly (ADP-ribose) polymerase cleavage. However, in the presence of a pan-caspase inhibitor, PD-mediated growth inhibition and apoptosis were significantly protected. PD also destroyed the integrity of mitochondria due to the loss of MMP, leading to cytosolic release of cytochrome c. Moreover, the levels of ROS were markedly increased by PD treatment, which was significantly attenuated by the ROS scavenger N-acetyl-L-cysteine (NAC). Furthermore, NAC fully suppressed PDinduced apoptotic events and cytotoxicity. Conclusions:The results of this study show that PD had chemopreventive potential through the induction of ROS-dependent apoptosis in PC3 cells, and that this compound could be useful for developing an effective and selective natural source to inhibit cancer cell proliferation.

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[RETRACTED ARTICLE] Suppressive effect of platycodin D on bladder cancer through microRNA-129-5p-mediated PABPC1/PI3K/AKT axis inactivation

Cited by 8 publications

References 40 publications

Induction of apoptosis through inactivation of ROS-dependent PI3K/Akt signaling pathway by platycodin D in human bladder urothelial carcinoma cells

Induction of apoptosis through inactivation of ROS-dependent PI3K/Akt signaling pathway by platycodin D in human bladder urothelial carcinoma cells

Platycodin D sensitizes KRAS-mutant colorectal cancer cells to cetuximab by inhibiting the PI3K/Akt signaling pathway

Induction of ROS-dependent apoptotic cell death by platycodin D in human prostate cancer PC3 cells

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