Abstract
Citrus folium and its main ingredient nobiletin (NOB) have received widespread attention in recent years due to their antitumor effects. The antitumor effect of Citrus folium is related to the traditional use, mainly in its Chinese medicinal properties of soothing the liver and promoting qi, resolving phlegm, and dispelling stagnation. Some studies have proved that Citrus folium and NOB are more effective for triple-negative breast cancer (TNBC), which is related to the syndrome of stagnation of liver qi. From the perspective of modern biomedical research, NOB has anticancer effects. Its potential molecular mechanisms include inhibition of the cell cycle, induction of apoptosis, and inhibition of angiogenesis, invasion, and migration. Citrus folium and NOB can also reduce the side effects of chemotherapy drugs and reverse multidrug resistance (MDR). However, more research studies are needed to clarify the underlying mechanisms. The modern evidence of Citrus folium and NOB in breast cancer treatment has a strong connection with the traditional concepts and laws of applying Citrus folium in Chinese medicine (CM). As a low-toxic anticancer drug candidate, NOB and its structural changes, Citrus folium, and compound prescriptions will attract scientists to use advanced technologies such as genomics, proteomics, and metabolomics to study its potential anticancer effects and mechanisms. On the contrary, there are relatively few studies on the anticancer effects of Citrus folium and NOB in vivo. The clinical application of Citrus folium and NOB as new cancer treatment drugs requires in vivo verification and further anticancer mechanism research. This review aims to provide reference for the treatment of breast cancer by Chinese medicine.
Highlights
According to the latest data from the International Agency for Research on Cancer (IARC) in 2018, the incidence of breast cancer (BC) in female cancers worldwide is 24.2%, ranking first among female cancers, which is the main cause of female cancer deaths [1]
We have discovered from the compound prescriptions that Citrus folium is commonly used to treat BC as Chinese medicine (CM)
Every publication in English that was reviewed for this study was extracted from the PubMed, Embase, Web of Science, and CNKI databases restricted to the Medical Subject Headings Index (MeSH/DeCS) to April 2021. e search was based on different combinations of the following keywords: “Citrus folium,” “Folium citrus reticulate,” “nobiletin,” “NOB,” “mechanism,” “anti-breast-cancer,” and “pharmacology.” we reviewed the references in the selected articles for additional reports not included in the original article search
Summary
According to the latest data from the International Agency for Research on Cancer (IARC) in 2018, the incidence of breast cancer (BC) in female cancers worldwide is 24.2%, ranking first among female cancers, which is the main cause of female cancer deaths [1]. As one of the main complementary and alternative medicines, traditional Chinese medicine (TCM) has a history of thousands of years [11] It has the advantages of Evidence-Based Complementary and Alternative Medicine multiple targets, small side effects, and significant clinical effects in cancer treatment [12,13,14,15]. Citrus folium is derived from the leaves of the Rutaceae plant Tangerine and its cultivated varieties. It has the effects of soothing the liver, promoting qi, removing phlegm, and resolving mass. Modern pharmacological studies have shown that Citrus folium mainly contains volatile oil, carbohydrates, flavonoids, and other ingredients, which can effectively treat cough, pulmonary carbuncle, breast carbuncle, hypochondriac pain, abdominal distension, hernia, edema, etc. The material basis of its efficacy is still unclear, so the mechanism of BC treatment at the molecular level is worthy of further study
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