Neferine-induced apoptosis is dependent on the suppression of Bcl-2 expression via downregulation of p65 in renal cancer cells

Kim, Eunae; Sung, Eon‐Gi; Song, In‐Hwan; Kim, Joo-Young; Sung, Hwa-Jung; Sohn, Ho-Yong; Park, Jong-Yi; Lee, Tae-Jin

doi:10.1093/abbs/gmz061

Cited by 23 publications

(10 citation statements)

References 30 publications

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“…In addition, NEF is the best chemotherapeutic active drug to resist various types of cancer such as in liver, colorectal, and breast cancer cells 42‐45 . 42 Poornima et al, 42 discovered NEF 15 mg/kg.bw treated HepG2 cells showed upregulated the Bax & Bad apoptotic protein expressions while downregulated the Bcl‐2 protein.…”

Section: Discussionmentioning

confidence: 99%

Chemomodulatory effect of neferine on DMBA‐induced squamous cell carcinogenesis: Biochemical and molecular approach

Wang

Yuan

et al. 2020

Environmental Toxicology

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Background Neferine (NEF) is nontoxic, bisbenzylisoquinoline alkaloid is derived from the seed embryo of lotus, a familiar medicinal plant. Although several mechanisms have been planned, an evident antitumor action pathway of NEF on the oral tumor is still not known. In the current study, we aimed at investigating the protecting effect of NEF against experimental oral carcinoma and clarify its possible mechanism through the induction of apoptosis, proliferation, and inflammatory signaling pathways. Methods The experimental hamsters were divided into four groups (I‐IV) containing six hamsters each. The group I was control group, group II and III hamsters treated with 7,12‐dimethylbenz(a)anthracene (DMBA) (0.5%) alone, thrice in a week for 10 weeks, and group III and IV hamsters received oral supplementation of NEF at a concentration of 15 mg/kg bw. All the hamsters were sacrificed after 16 weeks. Results Our results revealed that DMBA treated hamsters exhibited 100% oral tumor cell formation with high‐tumor incidence (TI), tumor number (TN), tumor volume (TV), decreased levels of antioxidants, increased status of lipid peroxidation (LPO), and modulated the activities of liver marker agents as well as NF‐kB, cell proliferation (PCNA), and p53 proteins. NEF supplementation in DMBA treated hamsters, resulted in delayed lesion synthesis, and brought back the levels of the biochemical parameters. In addition, immunostaining of NF‐kB, PCNA, and p53 showed that they were inhibited by NEF. Conclusion Thus, NEF might be considered a better chemopreventive drug in an experimental model of home‐based primary care (HBPC). More research is necessary to study other pathways implicated in oral carcinomas and their modulation by NEF.

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Section: Discussionmentioning

confidence: 99%

Chemomodulatory effect of neferine on DMBA‐induced squamous cell carcinogenesis: Biochemical and molecular approach

Wang

Yuan

et al. 2020

Environmental Toxicology

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“…There is at least one study that evaluated the anticancer effects of N. nucifera in renal cancer. An investigation led by Kim et al [135] explored the anticancer effects of neferine on Caki-1 renal cancer cells. Neferine was found to exhibit a growth-inhibitory effect in a concentration-dependent manner and caused apoptosis through the downregulation of Bcl-2 and X-linked inhibitor of apoptosis (XIAP).…”

Section: Renal Cancermentioning

confidence: 99%

Lotus (Nelumbo nucifera Gaertn.) and Its Bioactive Phytocompounds: A Tribute to Cancer Prevention and Intervention

Bishayee

Patel

Sharma

et al. 2022

Cancers

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Cancer is one of the major leading causes of death worldwide. Accumulating evidence suggests a strong relationship between specific dietary habits and cancer development. In recent years, a food-based approach for cancer prevention and intervention has been gaining tremendous attention. Among diverse dietary and medicinal plants, lotus (Nelumbo nucifera Gaertn., family Nymphaeaceae), also known as Indian lotus, sacred lotus or Chinese water lily, has the ability to effectively combat this disease. Various parts of N. nucifera have been utilized as a vegetable as well as an herbal medicine for more than 2000 years in the Asian continent. The rhizome and seeds of N. nucifera represent the main edible parts. Different parts of N. nucifera have been traditionally used to manage different disorders, such as fever, inflammation, insomnia, nervous disorders, epilepsy, hypertension, cardiovascular diseases, obesity, and hyperlipidemia. It is believed that numerous bioactive components, including alkaloids, polyphenols, terpenoids, steroids, and glycosides, are responsible for its various biological and pharmacological activities, such as antioxidant, anti-inflammatory, immune-modulatory, antiviral, hepatoprotective, cardioprotective, and hypoglycemic activities. Nevertheless, there is no comprehensive review with an exclusive focus on the anticancer attributes of diverse phytochemicals from different parts of N. nucifera. In this review, we have analyzed the effects of N. nucifera extracts, fractions and pure compounds on various organ-specific cancer cells and tumor models to understand the cancer-preventive and therapeutic potential and underlying cellular and molecular mechanisms of action of this interesting medicinal and dietary plant. In addition, the bioavailability, pharmacokinetics, and possible toxicity of N. nucifera-derived phytochemicals, as well as current limitations, challenges and future research directions, are also presented.

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“…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%

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

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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.

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Neferine-induced apoptosis is dependent on the suppression of Bcl-2 expression via downregulation of p65 in renal cancer cells

Cited by 23 publications

References 30 publications

Chemomodulatory effect of neferine on DMBA‐induced squamous cell carcinogenesis: Biochemical and molecular approach

Chemomodulatory effect of neferine on DMBA‐induced squamous cell carcinogenesis: Biochemical and molecular approach

Lotus (Nelumbo nucifera Gaertn.) and Its Bioactive Phytocompounds: A Tribute to Cancer Prevention and Intervention

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

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