Antitumor functions and mechanisms of nitidine chloride in human cancers

Cui, Yue; Wu, Linhui; Cao, Ruoxue; Xu, Hui; Xia, Jun; Wang, Z. Peter; Ma, Jia

doi:10.7150/jca.37890

Cited by 39 publications

(35 citation statements)

References 62 publications

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“…One of the key advantages of using natural products instead of synthetic compounds in drug discovery is that natural products are likely to be multi-target compounds. Nitidine is a common alkaloid found in many Zanthoxylum species, and it has been reported to suppress cell proliferation, to stimulate apoptosis, to induce cell cycle arrest, and to retard migration, invasion and metastasis in a variety of malignancies via multiple molecular mechanisms (Cui et al, 2020;Nhiem et al, 2020). In this work, we unveil a potential polypharmacological capacity for nitidine, which might be responsible for its synthetic lethal activity against BRCA1-deficient cells.…”

Section: Discussionmentioning

confidence: 88%

“…It was described to have anti-inflammatory, anti-parasitic, and antifungal properties (Nhiem et al, 2020). Interestingly, this metabolite was reported to possess potent antitumor activities by inhibiting proliferation and inducing apoptosis in several types of cancer models (Chen et al, 2012;Liao et al, 2013;Fang et al, 2013;Cui et al, 2020;Nhiem et al, 2020). Since oxynitidine is the 6-oxo analogue of nitidine, we decided to test whether nitidine also depicts selective cytotoxicity against BRCA1-deficient cells.…”

Section: The Commercially Available Alkaloid Nitidine Is a Powerful Smentioning

confidence: 99%

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Synthetic Lethal Activity of Benzophenanthridine Alkaloids From Zanthoxylum coco Against BRCA1-Deficient Cancer Cells

et al. 2020

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Several plants from South America show strong antitumoral properties based on anti-proliferative and/or pro-apoptotic activities. In this work we aimed to identify selective cytotoxic compounds that target BRCA1-deficient cancer cells by Synthetic Lethality (SL) induction. Using a high-throughput screening technology developed in our laboratory, we analyzed a collection of extracts from 46 native plant species from Argentina using a wide dose-response scheme. A highly selective SL-induction capacity was found in an alkaloidal extract from Zanthoxylum coco (Fam. Rutaceae). Bio-guided fractionation coupled to HPLC led to the identification of active benzophenanthridine alkaloids. The most potent SL activity was found with the compound oxynitidine, which showed a remarkably low relative abundance in the active fractions. Further validation experiments were performed using the commercially available and closely related analog nitidine, which showed SL-induction activity against various BRCA1-deficient cell lines with different genetic backgrounds, even in the nanomolar range. Exploration of the underlying mechanism of action using BRCA1-KO cells revealed AKT and topoisomerases as the potential targets responsible of nitidine-triggered SL-induction. Taken together, our findings expose an unforeseen therapeutic activity of alkaloids from Zanthoxylum-spp. that position them as novel lead molecules for drug discovery.

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Section: Discussionmentioning

confidence: 88%

Section: The Commercially Available Alkaloid Nitidine Is a Powerful Smentioning

confidence: 99%

Synthetic Lethal Activity of Benzophenanthridine Alkaloids From Zanthoxylum coco Against BRCA1-Deficient Cancer Cells

et al. 2020

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“…Previous studies revealed that NC has multiple pharmacological functions, such as anti-fungal, anti-inflammatory, and anti-oxidant properties 14 , 15 . Recently, several studies revealed tumor-suppressive functions of NC in various types of human malignant cancers 16 – 19 . As a natural anti-cancer drug, NC has received extensive attention.…”

Section: Introductionmentioning

confidence: 99%

Nitidine chloride possesses anticancer property in lung cancer cells through activating Hippo signaling pathway

Zhang

Lian

et al. 2020

Cell Death Discov.

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Nitidine chloride (NC) has significant anti-tumor properties; however, the precise mechanism related to NC still needs further investigation. This study intends to investigate the anti-tumor functions and the feasible molecular basis of NC in NSCLC cells. Therefore, we determined the mechanism of NC-mediated anti-tumor function through various methods. Cell proliferation ability and migration and invasion were detected by CCK-8, colony formation assay and Transwell assay, respectively. Furthermore, flow cytometry was used to detect apoptosis, cell cycle and ROS. Moreover, protein expression level was measured by western blot. Our results showed that NC can inhibit the growth, motility of NSCLC cells, induce apoptosis and arrest cell cycle. Meanwhile, NC increased the level of ROS in NSCLC cells. Moreover, western blot data showed that NC suppressed the expression of Lats1, Mob1, and YAP, and enhanced the expression of p-Lats1, p-Mob1, p-YAP1 (ser127). Overall, our research reveals that NC exerts anticancer activity by activating and modulating the Hippo signaling pathway.

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“…Nitidine chloride (NC) has been identified as a phytochemical alkaloid that possessed antifungal, antioxidant and anticancer properties [ 6 ]. Accumulated evidence has suggested that NC exerts a tumor suppressive effect via targeting multiple signaling pathways in various human cancers [ 6 ]. NC reduced the cell migratory and invasive ability by repressing the c-Src/focal adhesion kinase (FAK) pathway in mammary carcinoma [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Nitidine chloride suppresses NEDD4 expression in lung cancer cells

Zhang

Cao

Lian

et al. 2020

Aging

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Nitidine chloride (NC) possesses anticancer properties in various types of human malignancies. However, the effects of NC on lung cancer cells have not been elucidated. Moreover, the molecular mechanism of NC-involved antitumor activity is unclear. Therefore, we aimed to determine the biological effect of NC and the underlying molecular insights in lung cancer cells. The antineoplastic function of NC was assessed by MTT assays, Annexin V-FITC/PI apoptosis assay, wound healing analysis, and Transwell chamber migration and invasion assay in lung cancer cells. NEDD4 modulation was evaluated by western blotting assays of lung cancer cells after NC treatments. NEDD4 overexpression and downregulation were employed to validate the critical role of NEDD4 in the NC-mediated tumor suppressive effects. We found that NC suppressed cell viability, migration and invasion, but induced apoptosis in lung cancer cells. Mechanistic exploration revealed that NC exhibited its antitumor effects by reducing NEDD4 expression. Furthermore, our rescue experiments dissected that overexpression of NEDD4 abrogated the NC-mediated antineoplastic effects in lung cancer cells. Consistently, downregulation of NEDD4 enhanced the NC-induced anticancer effects. Thus, NC is a promising antitumor agent in lung cancer, indicating that NC might have potential therapeutic applications in the treatment of lung cancer.

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Antitumor functions and mechanisms of nitidine chloride in human cancers

Cited by 39 publications

References 62 publications

Synthetic Lethal Activity of Benzophenanthridine Alkaloids From Zanthoxylum coco Against BRCA1-Deficient Cancer Cells

Synthetic Lethal Activity of Benzophenanthridine Alkaloids From Zanthoxylum coco Against BRCA1-Deficient Cancer Cells

Nitidine chloride possesses anticancer property in lung cancer cells through activating Hippo signaling pathway

Nitidine chloride suppresses NEDD4 expression in lung cancer cells

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