A novel anticancer agent, icaritin, induced cell growth inhibition, G1 arrest and mitochondrial transmembrane potential drop in human prostate carcinoma PC-3 cells

Huang, Xin; Zhu, Danyan; Lou, Yijia

doi:10.1016/j.ejphar.2007.02.039

Cited by 127 publications

(78 citation statements)

References 29 publications

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“…3B). Cancer cell growth arrest at G0/G1 phase by influencing the function of cyclin D1 and Cdk4 was also reported by other researchers (23,24). These data suggest that the G0/G1 phase cell growth arrest in MAT-LyLu cells by GP is mediated through the downregulation of Cdk4 and cyclin D1, which further results in down-regulation of phosphorylation of Rb protein.…”

Section: Effect Of Gp On the Expression Of Cell Cycle-regulated Protesupporting

confidence: 61%

Gossypol inhibits the growth of MAT-LyLu prostate cancer cells by modulation of TGFβ/Akt signaling

Jiang

Ye²,

Lin³

2009

Int J Mol Med

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Abstract. Gossypol (GP), a male contraceptive compound naturally present in cottonseed products, possesses antiproliferative and anti-metastatic effects in vitro and in vivo. However, the detailed mechanisms responsible for the effects of GP on the cell cycle of prostate cancer cells remain to be elucidated. In the present study, we investigated the effects of GP on the regulation of the cell cycle of rodent prostate cancer MAT-LyLu cells and the mechanisms of GP-induced growth inhibition. Our results showed that GP inhibited the cell proliferation and colony formation in a dose-dependent manner by the up-regulation of expression and secretion of transforming growth factor ß1 (TGFß1) and down-regulation of expression of Akt and phospho-Akt protein. The inhibition of cell growth was also demonstrated by cell cycle arrest at G0/G1 phase. Furthermore, GP decreased the expression of cyclin D1, Cdk4 and phospho-Rb in MAT-LyLu cells. Thus, the inhibitory effects of GP on the proliferation of MAT-LyLu prostate cancer cells are associated with modulation of TGFß1 and Akt signaling, which influence the expression of regulatory proteins such as cyclin D1, Cdk4 and phospho-Rb which regulate cell cycle progression of prostate cancer cells.

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Section: Effect Of Gp On the Expression Of Cell Cycle-regulated Protesupporting

confidence: 61%

Gossypol inhibits the growth of MAT-LyLu prostate cancer cells by modulation of TGFβ/Akt signaling

Jiang

Ye²,

Lin³

2009

Int J Mol Med

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“…The mechanisms underlying the antitumor activity of icaritin have drawn increasing attention [5,6,[18][19][20] . Although accumulating evidence has shown that icaritin plays a potential role in inhibiting cancer cell growth, the underlying mechanism remains elusive.…”

Section: Introductionmentioning

confidence: 99%

“…However, the rate has been stagnant for 30 years, and disease prognosis is particularly poor for patients with recurrent and metastatic disease, partially due to the emergence of chemotherapy resistance. The abnormal control of cell proliferation in osteosarcoma has been linked to the suppression of apoptosis [15] , increased MMP expression [12,16] and the genetic alteration of oncogenes that regulate the cell cycle [17,18] .…”

Section: Introductionmentioning

confidence: 99%

Icaritin suppresses the proliferation of human osteosarcoma cells in vitro by increasing apoptosis and decreasing MMP expression

Wang

2014

Acta Pharmacol Sin

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Aim: To explore whether icaritin, a prenylflavonoid derivative of the Chinese tonic herb Epimedium, could suppress the proliferation of human osteosarcoma cells in vitro, and to elucidate the mechanisms of the action. Methods: Human osteosarcoma SaOS 2 cell line was used in the present study. The proliferation of the cells was examined using MTT assay and immunofluorescence DAPI staining. Cell motility was studied with the scratch assay. Cell apoptosis was determined by Annexin V-FITC and PI double staining using flow cytometry. Western blotting and RT-PCR were used to measure the expression of mRNAs and proteins in the cells. Results: Icaritin (5-15 μmol/L) suppressed the proliferation of SaOS 2 cells in vitro in a dose-dependent manner. Furthermore, the cell motility was significantly decreased after exposure to icaritin. Moreover, icaritin (5 μmol/L) time-dependently induced the apoptosis of SaOS 2 cells, markedly suppressed MMP-2 and MMP-9 expression, upregulated caspase-3 and caspase-9 expression, and increased the level of cleaved caspase-3 in the cells. Co-exposure to the caspase-3 inhibitor zVAD-fmk (10 μmol/L) compromised the icaritininduced caspase-3 expression and apoptosis in SaOS 2 cells. Conclusion: Icaritin suppresses the proliferation of SaOS 2 human osteosarcoma cells by increasing apoptosis and downregulating MMP expression.

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“…A modified Arrhenius equation (eq.2) was used to calculate the activation energy required for carrier-mediated transport: (2) Where E a is the activation energy (kcal/mol), R is the gas constant (0.001987 kcal/mol·K), T (K) is the absolute temperature, and A is the Arrhenius constant.…”

Section: Discussionmentioning

confidence: 99%

“…1) are widely distributed in the plant world and have a variety of biological effects including anticancer and anti-aging (e.g., alleviating aging-related degenerative diseases) (1)(2)(3). Prenylated flavonoids also serve as lead compounds to the development of novel estrogen receptor agonists and antagonists (4).…”

Section: Introductionmentioning

confidence: 99%

Intestinal Absorption Mechanisms of Prenylated Flavonoids Present in the Heat-Processed Epimedium koreanum Nakai (Yin Yanghuo)

et al. 2008

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Purpose-The purpose is to determine absorption mechanism of five bioactive prenylated flavonoids (baohuoside I, icariin, epimedine A, B, and C) present in heat-processed Epimedium koreanum Nakai (Yin Yanghuo).Methods-Transport of five prenylated flavonoids present in heat-processed herbs were studied in the human intestinal Caco-2 model and the perfused rat intestinal model.Results-In the perfused rat intestinal model, prenylated flavonoids with a monoglucosidic bond (e.g., icariin) was rapidly hydrolyzed into corresponding metabolites (e.g., baohuoside I). In the Caco-2 model, apical to basolateral permeability of a monoglycoside baohuoside I (1.46 ×10 −6 cm/ sec) was more than 2 folds greater than four prenylated flavonoids with 2 or more sugar moieties (<0.6×10 −6 cm/sec). The slow apical to basolateral transport of baohuoside I was the result of efflux. This efflux was carrier-mediated and active since its transport was vectorial, concentration-and temperature-dependent with activation energies greater than 15 kcal/mol. Efflux of baohuoside I was significantly suppressed by inhibitors of BCRP and MRP2, whereas efflux of icariin was significantly inhibited only by p-glycoprotein inhibitor verapamil. Because YHH is often heat-processed for better efficacy, we determined and found the optimal condition for increasing contents of more bioavailable flavonoids (i.e., baohuoside I) to be 160-170°C for 5-7 min.Conclusions-Poor bioavailability of prenylated flavonoids results from their poor intrinsic permeation and transporter-mediated efflux. Heat processing parameters may be optimized to preserve the herb's bioavailable flavonoids, which help retain and improve its efficacy during processing.

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A novel anticancer agent, icaritin, induced cell growth inhibition, G1 arrest and mitochondrial transmembrane potential drop in human prostate carcinoma PC-3 cells

Cited by 127 publications

References 29 publications

Gossypol inhibits the growth of MAT-LyLu prostate cancer cells by modulation of TGFβ/Akt signaling

Gossypol inhibits the growth of MAT-LyLu prostate cancer cells by modulation of TGFβ/Akt signaling

Icaritin suppresses the proliferation of human osteosarcoma cells in vitro by increasing apoptosis and decreasing MMP expression

Intestinal Absorption Mechanisms of Prenylated Flavonoids Present in the Heat-Processed Epimedium koreanum Nakai (Yin Yanghuo)

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