Neferine induces apoptosis by modulating the ROS‑mediated JNK pathway in esophageal squamous cell carcinoma

An, Kang; Zhang, Yuehan; Liu, Yingjiao; Yan, Shengxi; Hou, Zhenshan; Cao, Meng; Liu, Guangkuo; Dong, Congcong; Gao, Jie; Liu, Gaifang

doi:10.3892/or.2020.7675

Cited by 21 publications

(16 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, the leaf extract of lotus inhibited proliferation and metastasis of breast cancer cells (Yang, Hung, et al., 2019) and the stamen extract was found to be cytotoxic to colon cancer cells (Zhao et al., 2017). Neferine, an alkaloid derived from green seed embryos of lotus has been shown to have antiproliferative potential in hepatocellular carcinoma (Yoon et al., 2013), ovarian cancer (Xu et al., 2016), renal cancer (Kim et al., 2019), cervical cancer (Dasari et al., 2020), esophageal squamous cell carcinoma (An et al., 2020), osteosarcoma cells and NSCLC cells (Poornima et al., 2013). Flavonoids from leaf extract of lotus was also reported to inhibit growth of breast cancer cells as well as xenografts in mouse model (Chang et al., 2016).…”

Section: Discussionmentioning

confidence: 99%

“…For example, stamen extract of lotus induced apoptosis of colon carcinoma cell by increase or decrease of expression of apoptosis‐associated genes such as Fas and Fas ligand or anti‐apoptotic gene such as Bcl‐2, respectively (Dasari et al., 2020; Zhao et al., 2017). In NSCLC cells, neferine was evaluated as an apoptosis inducer through reactive oxygen species (ROS) generation (Kalai Selvi et al., 2017; Poornima et al., 2013) and MAPKs’ activation (An et al., 2020). Isoliensinine, an alkaloid from lotus embryo, was shown to cause apoptosis of hepatocellular carcinoma via suppression of NF‐κB signaling (Shu et al., 2015).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Lotus ( Nelumbo nucifera ) seedpod extract inhibits cell proliferation and induces apoptosis in non‐small cell lung cancer cells via downregulation of Axl

et al. 2020

View full text Add to dashboard Cite

Non-small-cell lung cancer (NSCLC) is the most frequent cause of cancer-related death. In this study, we found the anticancer activity of lotus seedpod extract (LSPE) in NSCLC cells, since LSPE treatment inhibited cell proliferation of A549 and H460 cells in a dose-dependent manner and the clonogenic activities of LSPE-treated cells were also reduced. In LSPE-treated cells, the cleavage of poly (ADP-ribose) polymerase (PARP) and phosphorylation of H2X, were also observed, indicating the pro-apoptotic effect of LSPE. Next, we found that LPSE treatment diminished the levels of protein and mRNA of Axl, a receptor tyrosine kinase (RTK) that transduces critical signals for cell proliferation and inhibition of apoptosis. The promoter activity of Axl was found to be dose-dependently decreased in response to LSPE treatment, implying that LSPE inhibited Axl gene expression at transcriptional level. In addition, Axl overexpression was found to decrease the effects of LSPE on inhibition of cell proliferation and colony formation as well as induction of PARP cleavage and phosphorylation of H2AX, while the same activities of LPSE were increased by knockdown of Axl gene expression, indicating that the antiproliferative and pro-apoptotic effect of LSPE is inversely proportional to the protein level of Axl. Taken together, we found that the LSPE suppressed cell proliferation and induced apoptosis of NSCLC cells, which is attenuated or augmented by overexpression or RNA interference of Axl expression, respectively. Our data suggest that Axl is a novel therapeutic target of LSPE to inhibit cell proliferation and promote apoptosis in NSCLC cells. Practical applications In this study, lotus seedpod extract (LSPE) was found to have the cytotoxic and apoptosis-inducing potentials in non-small-cell lung cancer (NSCLC) cells. LSPE downregulated the Axl expression at transcriptional level and the effects of LSPE on cell proliferation as well as apoptosis were affected by Axl protein level. Therefore, the inference of Axl-mediated intracellular signals by LSPE must be a novel approach to control NSCLC.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Lotus ( Nelumbo nucifera ) seedpod extract inhibits cell proliferation and induces apoptosis in non‐small cell lung cancer cells via downregulation of Axl

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Similarly, in KYSE30, KYSE150, and KYSE510 cell lines (esophageal squamous cell carcinoma (ESCC), neferine (15 μM) induces apoptosis through G2/M phase cell cycle arrest. In addition, the study reports ROS‐mediated activation of p‐JNK pathway and inhibition of nuclear factor erythroid 2–related factor 2 (Nrf2) by neferine leading to apoptosis‐mediated cell death (An et al., 2020). Neferine (6 μM) treatment along with cisplatin in colorectal cancer HCT‐15 cells increased the cellular uptake of cisplatin and induces ROS‐mediated apoptotic cell death through S phase cell cycle arrest and inhibiting cell survival proteins PI3K and p‐AKT thereby reduce the cisplatin dose requirement and potentiating the anti‐tumor efficacy of cisplatin (Manogaran et al., 2019).…”

Section: Pharmacological Properties Of Neferinementioning

confidence: 99%

An updated review on pharmacological properties of neferine—A bisbenzylisoquinoline alkaloid from Nelumbo nucifera

Priya

Huang

et al. 2021

J Food Biochem

View full text Add to dashboard Cite

Phytochemicals have recently received a lot of recognition for their pharmacological activities such as anticancer, chemopreventive, and cardioprotective properties. In traditional Indian and Chinese medicine, parts of lotus (Nelumbo nucifera) such as lotus seeds, fruits, stamens, and leaves are used for treating various diseases. Neferine is a bisbenzylisoquinoline alkaloid, a major component from the seed embryos of N. nucifera. Neferine is effective in the treatment of high fevers and hyposomnia, as well as arrhythmia, platelet aggregation, occlusion, and obesity. Neferine has been found to have a variety of therapeutic effects such as anti‐inflammatory, anti‐oxidant, anti‐hypertensive, anti‐arrhythmic, anti‐platelet, anti‐thrombotic, anti‐amnesic, and negative inotropic. Neferine also exhibited anti‐anxiety effects, anti‐cancerous, and chemosensitize to other anticancer drugs like doxorubicin, cisplatin, and taxol. Induction of apoptosis, autophagy, and cell cycle arrest are the key pathways that underlying the anticancer activity of neferine. Therefore, the present review summarizes the neferine biosynthesis, pharmacokinetics, and its effects in myocardium, cancer, chemosensitizing to cancer drug, central nervous system, diabetes, inflammation, and kidney diseases. Practical applications Natural phytochemical is gaining medicinal importance for a variety of diseases like including cancer, neurodegenerative disorder, diabetes, and inflammation. Alkaloids and flavonoids, which are abundantly present in Nelumbo nucifera have many therapeutic applications. Neferine, a bisbenzylisoquinoline alkaloid from N. nucifera has many pharmacological properties. This present review was an attempt to compile an updated pharmacological action of neferine in different disease models in vitro and in vivo, as well as to summarize all the collective evidence on the therapeutic potential of neferine.

show abstract

“…Although not explored by the authors, the data indicate that AUF1 downregulation causes NOS uncoupling via GTPCH1 regulation in ESCC cells. Since ESCC growth suppression was triggered by endoplasmic reticulum stress activation and increased ROS levels [97,98], NOS uncoupling can be associated with oxidative stress-induced cell death. However, to confirm this hypothesis BH4, BH4/BH2, and O 2…”

Section: Cell Growthmentioning

confidence: 99%

The Role of the BH4 Cofactor in Nitric Oxide Synthase Activity and Cancer Progression: Two Sides of the Same Coin

Gonçalves

Jasiulionis

Melo

2021

IJMS

View full text Add to dashboard Cite

Cancer development is associated with abnormal proliferation, genetic instability, cell death resistance, metabolic reprogramming, immunity evasion, and metastasis. These alterations are triggered by genetic and epigenetic alterations in genes that control cell homeostasis. Increased reactive oxygen and nitrogen species (ROS, RNS) induced by different enzymes and reactions with distinct molecules contribute to malignant transformation and tumor progression by modifying DNA, proteins, and lipids, altering their activities. Nitric oxide synthase plays a central role in oncogenic signaling modulation and redox landscape. Overexpression of the three NOS isoforms has been found in innumerous types of cancer contributing to tumor growth and development. Although the main function of NOS is the production of nitric oxide (NO), it can be a source of ROS in some pathological conditions. Decreased tetrahydrobiopterin (BH4) cofactor availability is involved in NOS dysfunction, leading to ROS production and reduced levels of NO. The regulation of NOSs by BH4 in cancer is controversial since BH4 has been reported as a pro-tumoral or an antitumoral molecule. Therefore, in this review, the role of BH4 in the control of NOS activity and its involvement in the capabilities acquired along tumor progression of different cancers was described.

show abstract

Neferine induces apoptosis by modulating the ROS‑mediated JNK pathway in esophageal squamous cell carcinoma

Cited by 21 publications

References 46 publications

Lotus ( Nelumbo nucifera ) seedpod extract inhibits cell proliferation and induces apoptosis in non‐small cell lung cancer cells via downregulation of Axl

Lotus ( Nelumbo nucifera ) seedpod extract inhibits cell proliferation and induces apoptosis in non‐small cell lung cancer cells via downregulation of Axl

An updated review on pharmacological properties of neferine—A bisbenzylisoquinoline alkaloid from Nelumbo nucifera

The Role of the BH4 Cofactor in Nitric Oxide Synthase Activity and Cancer Progression: Two Sides of the Same Coin

Contact Info

Product

Resources

About