Naringin Causes Cell Cycle Arrest and Cell Death in Nasal Cancer Cells

Jim Crocker
27th July, 2024

Naringin Causes Cell Cycle Arrest and Cell Death in Nasal Cancer Cells

Image Source: Natural Science News, 2024

Key Findings

  • Researchers from China Medical University, Taiwan, found that naringin, a compound in grapefruit, is effective against nasopharyngeal carcinoma (NPC) cells
  • Naringin stops NPC cells from dividing by causing cell cycle arrest at the G1 phase
  • Naringin induces programmed cell death (apoptosis) in NPC cells through mitochondrial dysfunction and other pathways
Nasopharyngeal carcinoma (NPC) is a type of cancer that originates in the nasopharynx, the area behind the nose and above the back of the throat. It is particularly prevalent in certain geographic regions such as southern China, and its development has been linked to various factors including genetic predisposition, environmental influences, and viral infections, notably the Epstein-Barr virus (EBV)[2]. Recent research from China Medical University, Taiwan, has explored the anticancer effects of naringin, a compound found in grapefruit and citrus, on NPC cells[1]. Naringin has shown promise in treating several types of cancer, including cervical, thyroid, colon, brain, liver, lung, and breast cancers. The current study aimed to investigate its effects specifically on nasopharyngeal carcinoma cells. Researchers found that naringin exhibits cytotoxicity towards NPC-TW 039 and NPC-TW 076 cells, with IC50 values (the concentration required to kill half the population of cells) of 372/328 µM and 394/307 µM for 24 or 48 hours, respectively. Importantly, naringin showed minimal toxicity towards normal gingival epithelial cells, indicating its potential as a targeted therapy for NPC. The study revealed that naringin induces cell cycle arrest at the G1 phase in NPC cells by downregulating proteins essential for cell cycle progression, such as cyclin D1, cyclin A, and CDK2, while upregulating p21, a protein that inhibits cell cycle progression. This arrest prevents the cells from dividing and proliferating uncontrollably. Furthermore, naringin triggers apoptosis (programmed cell death) in NPC cells. This process involves several changes, including cell shrinkage, membrane blebbing (formation of bulges in the cell membrane), and chromatin condensation (tightening of the DNA structure). Annexin V and PI staining techniques confirmed that naringin promotes both necrosis (uncontrolled cell death) and late apoptosis in these cells. The mechanism behind naringin-induced apoptosis involves a decline in mitochondrial membrane potential, leading to the release of cytochrome c, a protein that activates a cascade of events involving Apaf-1, caspase-9, and caspase-3, ultimately resulting in cell death. Additionally, naringin increases the expression of pro-apoptotic Bax and decreases anti-apoptotic Bcl-xL, disrupting the balance between these proteins and promoting apoptosis. The compound also enhances the expression of t-Bid, a protein linked to death receptor pathways. Naringin also induces endoplasmic reticulum (ER) stress-associated apoptosis. This is evidenced by increased levels of proteins such as IRE1, ATF-6, GRP78, GADD153, and caspase-12. These proteins play roles in the ER stress response, which can lead to cell death when the stress is prolonged or severe. Interestingly, the study found that naringin triggers the production of reactive oxygen species (ROS), which are chemically reactive molecules containing oxygen. The increase in ROS contributes to G1 arrest and apoptosis. When the researchers used an antioxidant, N-acetylcysteine, to inhibit ROS generation, they observed a prevention of G1 arrest and apoptosis, highlighting the critical role of ROS in naringin's anticancer effects. The findings from this study align with previous research that has explored the complex interplay of genetic, viral, and environmental factors in NPC. For example, the role of EBV in NPC has been well-documented, with variations in the virus's genetic sequence impacting cancer development[2]. Additionally, the increased risk of second primary cancers in NPC survivors underscores the need for effective treatments that can reduce the initial tumor burden and prevent recurrence[3]. The identification of biomarkers for NPC and other head and neck cancers has also been a focus, aiming to improve individualized cancer therapy[4]. In conclusion, the study from China Medical University demonstrates that naringin exhibits significant anticancer activity against nasopharyngeal carcinoma cells by inducing cell cycle arrest and apoptosis through multiple pathways, including mitochondrial dysfunction, death receptor signaling, ER stress, and ROS production. These findings suggest that naringin could be a promising therapeutic strategy for treating NPC, potentially improving outcomes for patients affected by this challenging disease.

MedicineHealthBiochem

References

Main Study

1) Naringin Induces ROS-Stimulated G1 Cell-Cycle Arrest and Apoptosis in Nasopharyngeal Carcinoma Cells.

Published 26th July, 2024

https://doi.org/10.1002/tox.24378

Related Studies

2) The Evolving Epidemiology of Nasopharyngeal Carcinoma.

https://doi.org/10.1158/1055-9965.EPI-20-1702

3) The incidence and risk of second primary cancers in patients with nasopharyngeal carcinoma: a population-based study in Taiwan over a 25-year period (1979-2003).

https://doi.org/10.1093/annonc/mdn003

4) Emerging biomarkers in head and neck cancer in the era of genomics.

https://doi.org/10.1038/nrclinonc.2014.192


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