Neferine induces autophagy of human ovarian cancer cells via p38 MAPK/ JNK activation

Xu, Limei; Li, Yinuo; Lu, Shu-Hua; Lu, Shan; Li, Jieyin; Wang, Yuqiong; Tian, Xiaoxue; Wei, Jian Jun; Shao, Changshun; Liu, Zhaojian

doi:10.1007/s13277-015-4737-8

Cited by 70 publications

(53 citation statements)

References 25 publications

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“…In recent years, various studies have shown that neferine has a direct antitumor activity in various cancer cells including ovarian cancer, hepatocellular carcinoma, lung cancer, osteosarcoma, and neuroblastoma in vitro and in vivo (Pham et al., ; Poornima et al., ; Xu et al., ; Yoon et al., ; Zhang et al., ). Moreover, neferine acts as a chemosensitizer, sensitizing cancer cells to chemotherapeutic agents and reversing multidrug resistance.…”

Section: Discussionmentioning

confidence: 99%

Neferine in the Lotus Plumule Potentiates the Antitumor Effect of Imatinib in Primary Chronic Myeloid Leukemia Cells In Vitro

Zhang

Xiao

Dong

et al. 2019

Journal of Food Science

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Imatinib, the prototype BCR‐ABL tyrosine kinase inhibitor (TKI), is the first‐line treatment for Philadelphia chromosome‐positive chronic myeloid leukemia (CML) in the chronic phase. However, a subgroup of patients exhibit poor response or experience relapse. This issue may be overcome by combination therapy using natural compounds. Neferine, a major bisbenzylisoquinoline alkaloid extracted from “lotus plumule” (seed embryo of lotus) commonly used in traditional Chinese medicine and tea, was used herein in the combination treatment of CML. The MTT assay showed that neferine exerted cytotoxicity in primary CML cells in a dose‐dependent manner. Moreover, low concentrations of neferine (4 and 8 µM) sensitized primary CML cells to imatinib (CI < 1), and significantly decreased its IC50 from 0.70 ± 0.10 to 0.32 ± 0.06 µM and 0.16 ± 0.02 µM, respectively. Cotreatment of neferine and imatinib significantly decreased the expression of BCR‐ABL protein and its molecular chaperone heat shock protein 90 (Hsp90) mRNA and protein levels, and further decreased phospho‐extracellular regulated protein kinase 1/2 (p‐Erk1/2) and myeloid cell leukemia (Mcl‐1) expression. These results suggest that neferine might be a potential imatinib sensitizer in CML treatment. Practical application In China, Lotus plumule, the green embryo of lotus, is used as a tea and as a source of herbal medicine in the treatment of anxiety, insomnia, spermatorrhea, and thirst. Additional, neferine, a bisbenzylisoquinoline alkaloid extracted from lotus plumule has been shown to have antitumor potential. Herein, the effect of neferine and imatinib cotreatment on primary CML cells obtained from CML patients was assessed, with a synergistic effect being observed between the two compounds. Therefore, neferine might be a promising natural compound to potentiate imatinib in CML patients.

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Section: Discussionmentioning

confidence: 99%

Neferine in the Lotus Plumule Potentiates the Antitumor Effect of Imatinib in Primary Chronic Myeloid Leukemia Cells In Vitro

Zhang

Xiao

Dong

et al. 2019

Journal of Food Science

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“…Neferine from green seed embryos of Nelumbo nucifera (Gaertn) is a bisbenzylisoquinoline alkaloid with cytotoxicity toward cancer cells (Poornima et al, 2014; Xu et al, 2016). It also revealed cell cycle arrest, apoptosis, endoplasmic reticulum stress, autophagy, as well as anti-angiogenic and anti-migratory effects in human hepatocellular carcinoma cells (Yoon et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…In traditional Chinese medicine, it has been widely used to treat nervous disorders, insomnia, high fevers with restlessness, as well as pulmonary and cardiovascular diseases such as hypertension, atherosclerosis, restenosis, and arrhythmia (Sridhar and Bhat, 2007; Jun et al, 2016; Sharma et al, 2017). Various studies pointed out the potential anti-cancer effect of neferine as well (Huang et al, 2011b; Yoon et al, 2013; Poornima et al, 2014; Xu et al, 2016). In this study, we evaluated the effect of neferine in terms of P-gp inhibition via in silico molecular docking, QSAR and in vitro cytotoxicity assays and P-gp substrate uptake assays in drug-resistant cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Mode of Action Analyses of Neferine, a Bisbenzylisoquinoline Alkaloid of Lotus (Nelumbo nucifera) against Multidrug-Resistant Tumor Cells

Kadioglu¹,

Law

Mok

et al. 2017

Front. Pharmacol.

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Neferine, a bisbenzylisoquinoline alkaloid isolated from the green seed embryos of Lotus (Nelumbo nucifera Gaertn), has been previously shown to have various anti-cancer effects. In the present study, we evaluated the effect of neferine in terms of P-glycoprotein (P-gp) inhibition via in vitro cytotoxicity assays, R123 uptake assays in drug-resistant cancer cells, in silico molecular docking analysis on human P-gp and in silico absorption, distribution, metabolism, and excretion (ADME), quantitative structure activity relationships (QSAR) and toxicity analyses. Lipinski rule of five were mainly considered for the ADME evaluation and the preset descriptors including number of hydrogen bond donor, acceptor, hERG IC50, logp, logD were considered for the QSAR analyses. Neferine revealed higher toxicity toward paclitaxel- and doxorubicin-resistant breast, lung or colon cancer cells, implying collateral sensitivity of these cells toward neferine. Increased R123 uptake was observed in a comparable manner to the control P-gp inhibitor, verapamil. Molecular docking analyses revealed that neferine still interacts with P-gp, even if R123 was pre-bound. Bioinformatical ADME and toxicity analyses revealed that neferine possesses the druggability parameters with no predicted toxicity. In conclusion, neferine may allocate the P-gp drug-binding pocket and prevent R123 binding in agreement with P-gp inhibition experiments, where neferine increased R123 uptake.

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“…Furthermore, Bahrami and colleagues indicated that monepantel induced autophagy in human ovarian cancer cells through disruption of the mTOR/p70S6K signalling pathway [44]. In contrast, activation of p38 MAPK and JNK signaling pathways contributed to the induction of autophagy in ovarian cancer cells [45–47]. For instance, Neferine induced autophagy of human ovarian cancer cells via p38 MAPK/JNK activation [47].…”

Section: Autophagy and Ovarian Carcinomamentioning

confidence: 99%

“…In contrast, activation of p38 MAPK and JNK signaling pathways contributed to the induction of autophagy in ovarian cancer cells [45–47]. For instance, Neferine induced autophagy of human ovarian cancer cells via p38 MAPK/JNK activation [47]. Inhibition of JNK3 could promote apoptosis and autophagy in chemoresistant human ovarian cancer cells [45].…”

Section: Autophagy and Ovarian Carcinomamentioning

confidence: 99%

Autophagy as an emerging therapy target for ovarian carcinoma

et al. 2016

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Autophagy is a conserved cellular self-digestion pathway for maintenance of homeostasis under basal and stressed conditions. Autophagy plays pivotal roles in the pathogenesis of many diseases, such as aging-related diseases, autoimmune diseases, cardiovascular diseases, and cancers. Of special note is that accumulating data suggest an intimate relationship between autophagy and ovarian carcinoma. Autophagy is well identified to act as either as a tumor-suppressor or as a tumor-promoter in ovarian carcinoma. The exact function of autophagy in ovarian carcinoma is highly dependent on the circumstances of cancer including hypoxic, nutrient-deficient, chemotherapy and so on. However, the mechanism underlying autophagy associated with ovarian carcinoma remains elusive, the precise role of autophagy in ovarian carcinoma also remains undetermined. In this review, we tried to sum up and discuss recent research achievements of autophagy in ovarian cancer. Moreover, waves of novel therapies ways for ovarian carcinoma based on the functions of autophagy were collected.

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Neferine induces autophagy of human ovarian cancer cells via p38 MAPK/ JNK activation

Cited by 70 publications

References 25 publications

Neferine in the Lotus Plumule Potentiates the Antitumor Effect of Imatinib in Primary Chronic Myeloid Leukemia Cells In Vitro

Neferine in the Lotus Plumule Potentiates the Antitumor Effect of Imatinib in Primary Chronic Myeloid Leukemia Cells In Vitro

Mode of Action Analyses of Neferine, a Bisbenzylisoquinoline Alkaloid of Lotus (Nelumbo nucifera) against Multidrug-Resistant Tumor Cells

Autophagy as an emerging therapy target for ovarian carcinoma

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