Piperlongumine Induces Apoptosis and Synergizes with Cisplatin or Paclitaxel in Human Ovarian Cancer Cells

Gong, Lihua; Chen, Xiuxiu; Wang, Huanhuan; Jiang, Qiwei; Pan, Shi-Shi; Qiu, Jian-Ge; Mei, Xiao-Long; Xue, Youqiu; Qin, Wu-Ming; Zheng, Fangfang; Shi, Zhi; Yan, Xiaojian

doi:10.1155/2014/906804

Cited by 65 publications

(69 citation statements)

References 27 publications

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“…A number of previous studies have noted G2/M arrest upon treatment with 1, including in Chinese hamster lung fibroblasts (V79), [29] OVCAR3 human ovarian cancer cells [30] and PC-3 prostate carcinoma cells [28].…”

Section: Effects Of Piperlongumine On the Cell Cycle And Apoptosismentioning

confidence: 99%

Piperlongumine (piplartine) and analogues: Antiproliferative microtubule-destabilising agents

Meegan

Nathwani

Twamley

et al. 2017

European Journal of Medicinal Chemistry

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Piperlongumine (piplartine, 1) is a small molecule alkaloid that is receiving intense interest due to its antiproliferative and anticancer activities. We investigated the effects of 1 on tubulin and microtubules. Using both an isolated tubulin assay, and a combination of sedimentation and Western blotting, we demonstrated that 1 is a tubulin-destabilising agent. This result was confirmed by immunofluorescence and confocal microscopy, which showed that microtubules in MCF-7 breast cancer cells were depolymerised when treated with 1. We synthesised a number of analogues of 1 to explore structure-activity relationships. Compound 13 had the best cytotoxic profile of this series, showing potent effects in human breast carcinoma MCF-7 cells whilst being relatively non-toxic to non-tumorigenic MCF-10a cells. These compounds will be further developed as potential clinical candidates for the treatment of breast cancer.3

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Section: Effects Of Piperlongumine On the Cell Cycle And Apoptosismentioning

confidence: 99%

Piperlongumine (piplartine) and analogues: Antiproliferative microtubule-destabilising agents

Meegan

Nathwani

Twamley

et al. 2017

European Journal of Medicinal Chemistry

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“…Treating HT-29 cells with MEK inhibitors partially effected piperlongumine induced apoptosis (Randhawa et al, 2013). Human ovarian G2/M phase arrest Gong et al (2014) cancer cells…”

Section: Phenethyl Isothiocyanatementioning

confidence: 99%

“…Piperlongumine has been shown to trigger production of Reactive Oxygen Species (ROS) in ovarian cancer cells. Combinatorial approach consisting of low dose of Piperlongumine / cisplatin or paclitaxel worked synergistically to exert biological effects (Gong et al, 2014). Piperlongumine treated prostate cancer cells displayed a marked decrease in NFKB activity and nuclear accumulation of p50 and p65 subunits was also inhibited (Ginzburg et al, 2014).…”

Section: Phenethyl Isothiocyanatementioning

confidence: 99%

Dealing Naturally with Stumbling Blocks on Highways and Byways of TRAIL Induced Signaling

Rana¹,

Attar²,

Qureshi³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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In-depth analysis of how TRAIL signals through death receptors to induce apoptosis in cancer cells using high throughput technologies has added new layers of knowledge. However, the wealth of information has also highlighted the fact that TRAIL induced apoptosis may be impaired as evidenced by experimental findings obtained from TRAIL resistant cancer cell lines. Overwhelmingly, increasing understanding of TRAIL mediated apoptosis has helped in identifying synthetic and natural compounds which can restore TRAIL induced apoptosis via functionalization of either extrinsic or intrinsic pathways. Increasingly it is being realized that biologically active phytochemicals modulate TRAIL induced apoptosis, as evidenced by cell-based studies. In this review we have attempted to provide an overview of how different phytonutrients have shown efficacy in restoring apoptosis in TRAIL resistant cancer cells. We partition this review into how the TRAIL mediated signaling landscape has broadened over the years and how TRAIL induced signaling machinery crosstalks with autophagic protein networks. Subsequently, we provide a generalized view of considerable biological activity of coumarins against a wide range of cancer cell lines and how coumarins (psoralidin and esculetin) isolated from natural sources have improved TRAIL induced apoptosis in resistant cancer cells. We summarize recent updates on piperlongumine, phenethyl isothiocyanate and luteolin induced activation of TRAIL mediated apoptosis. The data obtained from pre-clinical studies will be helpful in translation of information from benchtop to the bedside.

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“…Among the multivalent effects, the potential of piperlongumine as a novel anticancer agent have gained considerable attention recently. Emerging evidence suggests that piperlongumine is capable of killing multiple types of cancer cells, including Burkitt lymphoma (25), head and neck cancer (26), ovarian cancer (27), glioblastoma multiforme (28), breast cancer (29), prostate cancer (30), and colon cancer (31). This alkaloid was also found to sensitize tumors to chemotherapeutic agents such as cisplatin and paclitaxel (26,27).…”

Section: Introductionmentioning

confidence: 99%

“…Emerging evidence suggests that piperlongumine is capable of killing multiple types of cancer cells, including Burkitt lymphoma (25), head and neck cancer (26), ovarian cancer (27), glioblastoma multiforme (28), breast cancer (29), prostate cancer (30), and colon cancer (31). This alkaloid was also found to sensitize tumors to chemotherapeutic agents such as cisplatin and paclitaxel (26,27). Piperlongumine inhibits the growth of tumor cells with no apparent toxicity in nonmalignant human cells (32)(33)(34).…”

Section: Introductionmentioning

confidence: 99%

Piperlongumine Suppresses Growth and Sensitizes Pancreatic Tumors to Gemcitabine in a Xenograft Mouse Model by Modulating the NF-kappa B Pathway

Wang

Zhou

et al. 2016

Cancer Prevention Research

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Pancreatic cancer is an aggressive malignancy, which generally respond poorly to chemotherapy. Hence, novel agents that are safe and effective are highly needed. The aim of this study was to investigate whether piperlongumine, a natural product isolated from the fruit of the pepper Piper longum, has any efficacy against human pancreatic cancer when used either alone or in combination with gemcitabine in vitro and in a xenograft mouse model. In vitro, piperlongumine inhibited the proliferation of pancreatic cancer cell lines, potentiated the apoptotic effects of gemcitabine, inhibited the constitutive and inducible activation of NF-kB, and suppressed the NF-kB-regulated expression of c-Myc, cyclin D1, Bcl-2, Bcl-xL, Survivin, XIAP, VEGF, and matrix metalloproteinase-9 (MMP-9). Furthermore, in an in vivo xenograft model, we found piperlongumine alone significantly suppressed tumor growth and enhanced the antitumor properties of gemcitabine. These results were consistent with the downregulation of NF-kB activity and its target genes, decreased proliferation (PCNA and Ki-67), decreased microvessel density (CD31), and increased apoptosis (TUNEL) in tumor remnants. Collectively, our results suggest that piperlongumine alone exhibits significant antitumor effects against human pancreatic cancer and it further enhances the therapeutic effects of gemcitabine, possibly through the modulation of NF-kB-and NF-kB-regulated gene products.Cancer Prev Res; 9(3); 234-44. Ó2015 AACR.

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Piperlongumine Induces Apoptosis and Synergizes with Cisplatin or Paclitaxel in Human Ovarian Cancer Cells

Cited by 65 publications

References 27 publications

Piperlongumine (piplartine) and analogues: Antiproliferative microtubule-destabilising agents

Piperlongumine (piplartine) and analogues: Antiproliferative microtubule-destabilising agents

Dealing Naturally with Stumbling Blocks on Highways and Byways of TRAIL Induced Signaling

Piperlongumine Suppresses Growth and Sensitizes Pancreatic Tumors to Gemcitabine in a Xenograft Mouse Model by Modulating the NF-kappa B Pathway

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