Dioscorea nipponica Makino inhibits migration and invasion of human oral cancer HSC-3 cells by transcriptional inhibition of matrix metalloproteinase-2 through modulation of CREB and AP-1 activity

Chien, Ming Hsien; Ying, Tsung Ho; Hsieh, Yih Shou; Chang, Yi-Chun; Yeh, Chia Ming; Ko, Jiunn‐Liang; Lee, Wen Sen; Chang, Jer‐Hwa; Yang, Shun Fa

doi:10.1016/j.fct.2011.12.016

Cited by 61 publications

(55 citation statements)

References 49 publications

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“…Steroidal saponins are widely spread throughout the plant kingdom, an example being Dioscorea nipponica Makino, which is a famous traditional Chinese medicinal plant that has diversified pharmacological efficacies (Lu et al, 2010). It has been widely used in China for relieving cough and asthma, eliminating rheumatic aches, alleviating pain, improving blood circulation, and having antilipemic and anticancer properties (Kim et al, 2011;Chien et al, 2012;Kwon et al, 2003;Lu et al, 2014). Recently, the total saponins from Dioscorea nipponica Makino (TSDN) was reported to exert a hepatoprotective effect against CCl 4 -induced liver damage in mice through the suppression of inflammation and apoptosis .…”

Section: Introductionmentioning

confidence: 99%

Effects of the Total Saponins fromDioscorea nipponicaon Immunoregulation in Aplastic Anemia Mice

Wang

Yan

et al. 2015

Am. J. Chin. Med.

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Dioscorea nipponica Makino, a popular folk medicine, exerts anti-inflammation properties. The present study investigated the therapeutic effect of the total saponins from Dioscorea nipponica Makino (TSDN) on aplastic anemia (AA) and possible immune regulation mechanisms. Using a mouse model of AA, three different doses of TSDN were orally administrated for 14 consecutive days. We first demonstrated that TSDN was found to be effective in alleviating pancytopenia with a hypocellular bone marrow as compared with AA model group. Moreover, gastrogavage administration of a medium dose of TSDN was found to dramatically increase the percentage of CD4(+) cells in bone marrow nucleated cells (BMNC) and restore the CD4(+)/CD8(+) ratio. The pro-inflammatory cytokine concentrations of IL-2 and IFN-γ were significantly decreased, and anti-inflammatory cytokine IL-4 was significantly increased in culture supernatant of BMNC. Further investigations showed that TSDN obviously inhibited Fas-FasL-induced BMNC apoptosis as well as effectively suppressed intracellular apoptosis protein of caspase-3 and -8 expressions. Taken together, these findings suggested that TSDN could alleviate AA by elevating the CD4(+)/CD8(+) T-cell ratio, inhibiting inflammatory Th1-cytokines, and exerting anti-apoptosis effects.

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Section: Introductionmentioning

confidence: 99%

Effects of the Total Saponins fromDioscorea nipponicaon Immunoregulation in Aplastic Anemia Mice

Wang

Yan

et al. 2015

Am. J. Chin. Med.

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“…Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer which exhibits frequent lymph node metastasis and local invasion, causing poor prognosis (1,2). The addiction to betel, tobacco, and alcohol is found to be highly correlated with the risk of HNSCC (3) and the studies in this area might lead to new approaches in the prevention and treatment of this important group of human cancers (4).…”

Section: Introductionmentioning

confidence: 99%

AKT serine/threonine protein kinase modulates bufalin-triggered intrinsic pathway of apoptosis in CAL 27 human oral cancer cells

Tsai

Lee

et al. 2012

International Journal of Oncology

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Abstract. Bufalin has been reported to induce apoptosis in a variety of cancers but little is demonstrated in oral squamous cell carcinoma (OSCC) cells. The present study investigated the inhibition of proliferation, cell cycle arrest and apoptotic effects of bufalin in CAL 27 human oral cancer cells. Bufalin inhibited the growth of CAL 27 cells in a concentration-dependent manner and an IC 50 value of bufalin was about 125 nM for 24 h treatment using the MTT assay. Moreover, the cell cycle distribution was arrested at the G 0 /G 1 phase in CAL 27 cells after bufalin exposure. Upon bufalin stimulation, the expression of Bcl-2 was significantly decreased while that of cytochrome c, Apaf-1 and AIF was increased compared to the control group by western blot analysis. An increase in the expression of the active form of caspases was found in bufalin-treated cells, and the caspase activities were also elevated. Bufalin-triggered apoptosis was blocked by specific inhibitors of caspase-9 (z-LEHD-fmk) and caspase-3 (z-DEVD-fmk), respectively. In contrast, CAL 27 cells overexpressing constitutively active AKT (CAL 27/CA-AKT) were exposed to bufalin at different concentrations, and cell growth remained unchanged. Bufalin exhibited minimal apoptotic effects on CAL 27/CA-AKT cells. Taken together, bufalin induced G 0 /G 1 phase arrest and provoked the intrinsic apoptotic pathway via AKT activation in CAL 27 cells. Our data suggest that bufalin could be potentially efficacious in the treatment of oral cancer in the future.

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“…As evidenced by our results, EGCG/gefitinib combination treatment modulates anti-metastatic effects in an HNSCC culture system in vitro. 2 tissue culture flasks (TPP, Techno Plastic Products AG., Trasadingen, Switzerland) with DMEM supplemented with 10% FBS, 2 mM L-glutamine, 100 units/ml penicillin and 100 µg/ml streptomycin and grown at 37˚C in a humidified 5% CO 2 atmosphere and detached by 0.25% Trypsin/0.02% EDTA (38)(39)(40).…”

Section: Introductionmentioning

confidence: 99%

Epigallocatechin gallate sensitizes CAL-27 human oral squamous cell carcinoma cells to the anti-metastatic effects of gefitinib (Iressa) via synergistic suppression of epidermal growth factor receptor and matrix metalloproteinase-2

Chang

et al. 2012

Oncology Reports

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Abstract. Human head and neck squamous cell carcinoma (HNSCC) is a major cause of cancer-related death during the last decade due to its related metastasis and poor treatment outcomes. Gefitinib (Iressa), a tyrosine kinase inhibitor has been reported to reduce the metastatic abilities of oral cancer. Previous studies have shown that epigallocatechin gallate (EGCG), a green tea polyphenol, possesses cancer chemopreventive and anticancer activity. However, the mechanisms involved in the suppression of invasion and metastasis of human oral cancer cells following co-incubation with gefitinib and EGCG remain poorly understood. In the present study, we attempted to investigate the synergistic effects of a combined treatment of gefitinib and EGCG in CAL-27 cells in vitro and to elucidate the underlying molecular mechanisms associated with the supression of cell migration and invasion. In the present study, we found that the individual treatments or the combined treatment of gefitinib and EGCG synergistically inhibited the invasion and migration of CAL-27 cells using Transwell invasion and wound-healing scratch assays, respectively. Similarly, gefitinib in combination with EGCG synergistically attenuated enzymatic activity and the protein expression of MMP-2 in CAL-27 cells. Furthermore, individual or combined treatment with EGCG and gefitinib suppressed the protein expression of p-EGFR and the phosphorylated protein levels of ERK, JNK, p38 and AKT and displayed inhibitory effects on metastatic ability of CAL-27 cells. Combined effects of EGCG and gefitinib-altered anti-metastatic actions for related gene expression were observed using DNA microarray analysis. Importantly, EGCG sensitizes CAL-27 cells to gefitinib-suppressed phosphorylation of epidermal growth factor receptor (EGFR in vitro. Taken together, our results suggest that the synergistic suppression of the metastatic ability of CAL-27 cells after EGCG and gefitinib individual or combined treatment are mediated through mitogen-activated protein kinase (MAPK) signaling. Our novel findings provide potential insights into the mechanism involved with synergistic responses of gefitinib and EGCG against the progression of oral cancer.

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Dioscorea nipponica Makino inhibits migration and invasion of human oral cancer HSC-3 cells by transcriptional inhibition of matrix metalloproteinase-2 through modulation of CREB and AP-1 activity

Cited by 61 publications

References 49 publications

Effects of the Total Saponins fromDioscorea nipponicaon Immunoregulation in Aplastic Anemia Mice

Effects of the Total Saponins fromDioscorea nipponicaon Immunoregulation in Aplastic Anemia Mice

AKT serine/threonine protein kinase modulates bufalin-triggered intrinsic pathway of apoptosis in CAL 27 human oral cancer cells

Epigallocatechin gallate sensitizes CAL-27 human oral squamous cell carcinoma cells to the anti-metastatic effects of gefitinib (Iressa) via synergistic suppression of epidermal growth factor receptor and matrix metalloproteinase-2

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