Enhanced Antitumor Efficacy of Gemcitabine by Evodiamine on Pancreatic Cancer via Regulating PI3K/Akt Pathway

Wei, Wei‐Tian; Chen, Hui; Wang, Zhaohong; Ni, Zhonglin; Liu, Haibin; Tong, Hongfei; Guo, Hong-Chun; Liu, Dian-Lei; Lin, Shigang

doi:10.7150/ijbs.8.1

Cited by 65 publications

(53 citation statements)

References 46 publications

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“…The extract was dried on anhydrous Na 2 SO 4 , the EtOAc was removed and the crude product was purified by column chromatography to afford the pure target compounds. The characterization data for these compounds was as follows: (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Yellowish product 1.22 g, yield 53.8%, m.p.…”

Section: Synthesis Of N13-substituted Evodiamine Derivatives: Generalmentioning

confidence: 99%

“…(5 (6). This compound was obtained by the hydrolysis of 9-(2,2-diethoxyethyl)evodiamine (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Into a solution of 2-18 (1.26 g, 3.0 mmol) in ethanol (20 mL) was added 10% hydrochloric acid (10 mL), and the mixture was stirred for 4-5 h at room temperature, while monitored by TLC.…”

Section: Synthetic Procedures For 3-1-3-3mentioning

confidence: 99%

“…It was demonstrated by Hu [4] and Linag [1] that evodiamine possesses a wide range of biological activities related to anti-inflammatory, anti-obesity and antitumor properties. In particular, both the strong cytotoxicity of evodiamine against human cancer cells and the underlining mechanisms of growth inhibition, apoptosis induction and suppression of invasion and metastasis have attracted much attention [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Moreover, it was demonstrated that evodiamine sensitized chemoresistant breast cancer cells to adriamycin without obvious cytotoxicity against normal human peripheral blood cells [4,23], which indicated the potential of evodiamine for clinical application.…”

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis and Evaluation of N13-Substituted Evodiamine Derivatives against Human Cancer Cell Lines

Song

Chen

et al. 2013

Molecules

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Abstract:Attempting to improve the anticancer activity and solubility of evodiamine in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) solutions, thirty-eight N13-substituted evodiamine derivatives were designed, synthesized and tested for antitumor activities against six kinds of human cancer cell lines, namely prostate cancer (DU-145 and PC-3), lung cancer (H460), breast cancer (MCF-7), colon cancer (HCT-5) and glioblastoma (SF-268). The solubility of these compounds in SGF and SIF solutions was evaluated, and apoptosis induced by 2-2, 2-3, 2-16 and 3-2 was determined. The results showed: (1) among all compounds examined, 2-16 showed the highest antitumor activity and a broader spectrum of activity, with IC 50 values ranging from 1-2 µM; (2) their solubility was obviously improved; (3) 2-3, 2-16 and 3-2 had a significant impact inducing apoptosis in some cancer cell lines. The preliminary structure-activity relationships of these derivatives were discussed.

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Section: Synthesis Of N13-substituted Evodiamine Derivatives: Generalmentioning

confidence: 99%

Section: Synthetic Procedures For 3-1-3-3mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis and Evaluation of N13-Substituted Evodiamine Derivatives against Human Cancer Cell Lines

Song

Chen

et al. 2013

Molecules

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“…Jiang et al 40 reported that the IC 50 of GEM after a 48-h exposure is 16 μg/mL, and Celano et al 41 observed a significant effect at 100 μM GEM after a 72-h treatment. Cell viability in SW1990 cells, treated with 20 μM GEM, was reduced to 57% after 24 h. 42 Zhang et al 43 demonstrated that GEM induced a dose-and time-dependent decrease in the proliferation of the lung cancer cell line SPC-A-1. Compared with that of the control cells, SPC-A-1 cells showed a 60%, 35%, and 18% reduction in the levels …”

Section: Effect Of Agnps and Gem On Cell Viabilitymentioning

confidence: 99%

Silver nanoparticles enhance the apoptotic potential of gemcitabine in human ovarian cancer cells: combination therapy for effective cancer treatment

Yuan¹,

Peng²,

Gurunathan³

2017

IJN

126

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Background Gemcitabine (GEM) is widely used as an anticancer agent in several types of solid tumors. Silver nanoparticles (AgNPs) possess unique cytotoxic features and can induce apoptosis in a variety of cancer cells. In this study, we investigated whether the combination of GEM and AgNPs can exert synergistic cytotoxic effects in the human ovarian cancer cell line A2780. Methods We synthesized AgNPs using resveratrol as a reducing and stabilizing agent. The synthesized nanomaterials were characterized using various analytical techniques. The anticancer effects of a combined treatment with GEM and AgNPs were evaluated using a series of cellular assays. The expression of pro- and antiapoptotic genes was measured using real-time reverse transcription polymerase chain reaction. Apoptosis was confirmed by TUNEL assay. Results In this study, combined treatment with GEM and AgNPs significantly inhibited viability and proliferation in A2780 cells. Moreover, the levels of apoptosis in cells treated with a combination of GEM and AgNPs were significantly higher compared with those in cells treated with GEM or AgNPs alone. Our data suggest that GEM and AgNPs exhibit potent apoptotic activity in human ovarian cancer cells. Combined treatment with GEM and AgNPs showed a significantly higher cytotoxic effect in ovarian cancer cells compared with that induced by either of these agents alone. Conclusion Our study demonstrated that the interaction between GEM and AgNPs was cytotoxic in ovarian cancer cells. Combined treatment with GEM and AgNPs caused increased cytotoxicity and apoptosis in A2780 cells. This treatment may have therapeutic potential as targeted therapy for the treatment of ovarian cancer. To our knowledge, this study could provide evidence that AgNPs can enhance responsiveness to GEM in ovarian cancer cells and that AgNPs can potentially be used as chemosensitizing agents in ovarian cancer therapy.

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“…All animal studies were approved by the Animal Research and Ethical Committee of Wenzhou Medical College (Zhejiang, China). Pancreatic cancer xenograft tumor model was performed as described in our previous studies (25,26). PANC-1 cells (5x10 6 ) in 200 µl complete culture medium were injected subcutaneously into the right flank of each mouse.…”

Section: Real-time Polymerase Cahin Reaction (Pcr)mentioning

confidence: 99%

Involvement of the phosphoinositide 3-kinase/Akt pathway in apoptosis induced by capsaicin in the human pancreatic cancer cell line PANC-1

et al. 2012

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Abstract. Capsaicin, one of the major pungent ingredients found in red peppers, has been recently demonstrated to induce apoptosis in various malignant cell lines through an unclear mechanism. In this study, the effect of capsaicin on proliferation and apoptosis in the human pancreatic cancer cell line PANC-1 and its possible mechanism(s) of action were investigated. The results of a Cell Counting Kit-8 (CCK-8) assay revealed that capsaicin significantly decreased the viability of PANC-1 cells in a dose-dependent manner. Capsaicin induced G0/G1 phase cell cycle arrest and apoptosis in PANC-1 cells as demonstrated by a flow cytometric assessment. Caspase-3 expression at both the protein and mRNA level was promoted following capsaicin treatment. Furthermore, we revealed that phospho-PI3 Kinase p85 (Tyr458) and phospho-Akt (Ser473) in PANC-1 cells were downregulated in response to capsaicin. Moreover, capsaicin gavage significantly inhibited the growth of pancreatic cancer PANC-1 cell xenografts in athymic nude mice. An increased number of TUNEL-positive cells and cleaved caspase-3 were observed in capsaicin-treated mice. In vivo, capsaicin downregulated the expression of phospho-PI3 Kinase p85 (Tyr458) and phospho-Akt (Ser473).In conclusion, we have demonstrated that capsaicin is an inhibitor of growth of PANC-1 cells, and downregulation of the phosphoinositide 3-kinase/Akt pathway may be involved in capsaicin-induced apoptosis in vitro and in vivo.

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Enhanced Antitumor Efficacy of Gemcitabine by Evodiamine on Pancreatic Cancer via Regulating PI3K/Akt Pathway

Cited by 65 publications

References 46 publications

Design, Synthesis and Evaluation of N13-Substituted Evodiamine Derivatives against Human Cancer Cell Lines

Design, Synthesis and Evaluation of N13-Substituted Evodiamine Derivatives against Human Cancer Cell Lines

Silver nanoparticles enhance the apoptotic potential of gemcitabine in human ovarian cancer cells: combination therapy for effective cancer treatment

Involvement of the phosphoinositide 3-kinase/Akt pathway in apoptosis induced by capsaicin in the human pancreatic cancer cell line PANC-1

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