Platycodin D induces anoikis and caspase‐mediated apoptosis via p38 MAPK in AGS human gastric cancer cells

Chun, Jaemoo; Joo, Eun Ji; Kang, Minseok; Kim, Yeong Shik

doi:10.1002/jcb.24386

Cited by 80 publications

(78 citation statements)

References 51 publications

(37 reference statements)

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“…The inhibition of the activation of the p38 signal transduction pathway can induce apoptosis (28). p38 MAPK could promote apoptosis of lung adenocarcinoma cells via the regulation of the expression of the apoptosis-related proteins Bax and Bcl2 (29).…”

Section: Discussionmentioning

confidence: 99%

Silencing of FANCD2 enhances the radiosensitivity of metastatic cervical lymph node-derived head and neck squamous cell carcinoma HSC-4 cells

Feng

Bao

Zeng

et al. 2017

International Journal of Oncology

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Abstract. Fanconi anemia complementation group D2 (FANCD2) is involved in the key steps of the Fanconi anemia (FA) pathway, which plays a role in the repair of DNA crosslink damage. However, the role of FANCD2 during radiotherapy for head and neck squamous cell carcinoma (HNSCC) is unclear. In this study, the HNSCC cell line HSC-4 was used. Western blotting was used to evaluate the expression of the FANCD2 in HSC-4 cells. We investigated the impact of FANCD2 on the radiosensitivity of HSC-4 cells in vitro and in vivo. TUNEL, western blotting and immunohistochemistry were used to analyze the apoptosis and proteins involved in apoptosisrelated pathways after radiotherapy to investigate the relevant mechanism. The present study showed that shRNA interference could effectively and stably silence FANCD2 expression in HSC-4 cells. In vitro, the silencing of FANCD2 inhibited cell proliferation, decreased the survival rate, increased apoptosis and induced S phase arrest in HSC-4 cells after radiotherapy. In vivo, the silencing of FANCD2 could prolong the tumor-forming time and slow tumor growth. In addition, the tumor volume was significantly reduced, the weight was deceased, and the tumor inhibition rate was increased after radiotherapy. TUNEL showed that the silencing of FANCD2 significantly increased apoptosis in HSC-4 cells induced by radiotherapy. Both in vitro and in vivo esperiments revealed that the expression of the Bax and p-p38 proteins in HSC-4 cells, in which FANCD2 had been silenced, was increased after radiotherapy, whereas the expression of the p38 and Bcl2 proteins was decreased. Our results suggested that the silencing of FANCD2 enhanced the radiosensitivity of HSC-4 cells, and its mechanism involves the activation of the p38 MAPK signaling pathway and the regulation of the expression of Bax and Bcl2 proteins. This study provides a novel candidate target for HNSCC therapy.

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Section: Discussionmentioning

confidence: 99%

Silencing of FANCD2 enhances the radiosensitivity of metastatic cervical lymph node-derived head and neck squamous cell carcinoma HSC-4 cells

Feng

Bao

Zeng

et al. 2017

International Journal of Oncology

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“…Platycodin D (PD) is a triterpenoid saponin isolated from the Chinese medicinal herb Platycodonis Radix. It possesses important biological activities, including immune stimulation (Xie et al, 2008), anti-inflammation (Kim et al, 2001Ahn et al, 2005), anti-nociception (Choi et al, 2002), anti-obesity Lee et al, 2010), anti-atherosclerosis (Wu et al, 2012) and anti-cancer (Kim et al, 2005Kim et al, 2008a;Kim et al, 2008b;Shin et al, 2009;Choi et al, 2010;Yu and Kim, 2010;Chun et al, 2012) etc. Due to the various pharmacological activities, PD has been listed as the marker for the quality control of Platycodonis Radix in the Pharmacopoeia of the People's Republic of China (Pharmacopoeia Commission of the Ministry of Health of the P.R.…”

Section: Introductionmentioning

confidence: 99%

Platycodin D Induces Apoptosis, and Inhibits Adhesion, Migration and Invasion in HepG2 Hepatocellular Carcinoma Cells

T¹,

Xu²,

Wu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…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%

“…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, and anti-obesity effects (7), as well as spermicidal and contraceptive activity (8). 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).…”

Section: Introductionmentioning

confidence: 99%

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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Platycodin D induces anoikis and caspase‐mediated apoptosis via p38 MAPK in AGS human gastric cancer cells

Cited by 80 publications

References 51 publications

Silencing of FANCD2 enhances the radiosensitivity of metastatic cervical lymph node-derived head and neck squamous cell carcinoma HSC-4 cells

Silencing of FANCD2 enhances the radiosensitivity of metastatic cervical lymph node-derived head and neck squamous cell carcinoma HSC-4 cells

Platycodin D Induces Apoptosis, and Inhibits Adhesion, Migration and Invasion in HepG2 Hepatocellular Carcinoma Cells

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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