Mechanisms of Traditional Chinese medicine/natural medicine in HR-positive Breast Cancer: A comprehensive Literature Review.

ETHNOPHARMACOLOGICAL RELEVANCE: With the emergence of endocrine resistance, the survival and good prognosis of HR-positive breast cancer (HR + BC) patients are threatened. As a common complementary and alternative therapy in cancer treatment, traditional Chinese medicine (TCM) has been widely used, and its internal mechanisms have been increasingly explored. AIM OF THE REVIEW: In this review, the development status and achievements in understanding of the mechanisms related to the anti-invasion and anti-metastasis effects of TCM against HR + BC and the reversal of endocrine drug resistance by TCM in recent years have been summarized to provide ideas for antitumour research on the active components of TCM/natural medicine. METHODS: We searched the electronic databases PubMed, Web of Science, and China National Knowledge Infrastructure database (CNKI) (from inception to July 2023) with the key words "HR-positive breast cancer" or "HR-positive breast carcinoma", "HR + BC" and "traditional Chinese medicine", "TCM", or "natural plant", "herb", etc., with the aim of elucidating the intrinsic mechanisms of traditional Chinese medicine and natural medicine in the treatment of HR + BC. RESULTS: TCM/natural medicine monomers and formulas can regulate the expression of related genes and proteins through the PI3K/AKT, JAK2/STAT3, MAPK, Wnt and other signalling pathways, inhibit the proliferation and metastasis of HR + BC tumours, play a synergistic role in combination with endocrine drugs, and reverse endocrine drug resistance. CONCLUSION: The wide variety of TCM/natural medicine components makes the research and development of new methods of TCM for BC treatments more selective and innovative. Although progress has been made on research on TCM/natural medicine, there are still many problems in clinical and basic experimental designs, and more in-depth scientific explorations and research are still needed.

Compounds targeting ferroptosis in breast cancer: progress and their therapeutic potential.

In recent years, there has been a significant increase in the incidence of Breast cancer (BC), making it the most common cancer among women and a major threat to women's health. Consequently, there is an urgent need to discover new and effective strategies for treating BC. Ferroptosis, a novel form of cell death characterized by the accumulation of iron-dependent lipid reactive oxygen species, has emerged as a distinct regulatory pathway separate from necrosis, apoptosis, and autophagy. It is widely recognized as a crucial factor in the development and progression of cancer, offering a promising avenue for BC treatment. While significant progress has been made in understanding the mechanisms of ferroptosis in BC, drug development is still in its early stages. Numerous compounds, including phytochemicals derived from dietary sources and medicinal plants, as well as synthetic drugs (both clinically approved medications and laboratory reagents), have shown the ability to induce ferroptosis in BC cells, effectively inhibiting tumor growth. This comprehensive review aims to examine in detail the compounds that target ferroptosis in BC and elucidate their potential mechanisms of action. Additionally, the challenges associated with the clinical application of ferroptosis-inducing drugs are discussed, offering valuable insights for the development of novel treatment strategies for BC.

The expression of androgen receptor in triple-negative breast cancer and the effect of a traditional Chinese medicine formula on disease-free survival.

Background: Androgen receptor (AR) is becoming an important factor in the pathogenesis of breast cancer. Traditional Chinese medicine (TCM) is widely used in treating breast cancer patients. Triple-negative breast cancer (TNBC) is a subtype of breast cancer, which has worse prognosis than other subtypes. Herein, through this retrospective study, we summarize the therapeutic implications of AR and TCM in TNBC. Methods: The clinical and pathological data of TNBC patients who had undergone surgery at The First Affiliated Hospital of Zhejiang Chinese Medical University from 2017 to 2019 were collected and examined. The t-test, chi-square test, logistic regression model, and Kaplan-Meier survival estimates were used to analyze the data. Results: We identified 823 early breast cancer patients from January 2017 to December 2019, of whom 92 (11.2%) were pathologically confirmed to have TNBC. We excluded 5 patients according to the inclusion and exclusion criteria. In relation to the remaining 87 patients, 33 (37.9%) were AR positive. In the TNBC patients, positive AR expression was correlated with an older age (P=0.006), a higher weight (P=0.006), and lower Ki-67 expression (P=0.031). After a median follow-up time of 37 months (range, 24-60 months), 13 cases of relapse and metastasis (14.9%) were observed. We found that relapse and metastasis were correlated with being unmarried [P=0.004; hazard ratio (HR) =0.105; 95% confidence interval (95% CI): 0.023-0.487], nonporous (P=0.046; HR =0.209; 95% CI: 0.045-0.971), and negative AR expression (P=0.042; HR =1.223; 95% CI: 0.049-1.012). The AR-positive TNBC patients had better disease-free survival (DFS) than the AR-negative TNBC patients 2-5 years after surgery (P<0.05). TCM was an effective treatment for TNBC (P<0.001; HR =51.682; 95% CI: 6.660-401.025). In the AR-negative group, patients who received the TCM treatment tended to have a better DFS than those who did not receive the TCM treatment (P<0.001; HR =34.832; 95% CI: 4.448-272.756); however, no such difference was found in the AR-positive group. Conclusions: The TNBC patients with positive AR tended to have a low expression of Ki-67 and a better prognosis than AR negative TNBC patients. TCM is an effective treatment and has slight side effects.

Amorphophalli Rhizoma inhibits breast cancer growth, proliferation, migration, and invasion via the PI3K/AKT pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Amorphophalli Rhizoma (APR) is widely used as an adjuvant treatment for advanced and metastatic triple-negative breast cancer (TNBC), but its effects, potential active ingredients, and mechanism of action on estrogen receptor-positive (ER+) and human epidermal growth factor receptor-positive (HER2+) breast cancer cells were not reported. AIM OF THE STUDY: The present study investigated the effects and mechanism of APR on ER+ and HER2+ breast cancer cells. MATERIALS AND METHODS: Rotary evaporation was used to prepare different extracts of APR. Cell activity was assessed using the cell counting kit-8 (CCK-8) method. Wound healing assays were used to assess cell migration, and a cell invasion assay was performed using a Transwell chamber with Matrigel matrix. A xenograft model was used to analyze the inhibitory effects of APR on tumor growth. Bioinformatics analyses were used to explore the potential mechanism of APR in breast cancer. RT-qPCR and Western blotting were performed to reveal the molecular mechanism. RESULTS: The ethyl acetate extract of APR showed the strongest tumor inhibitory effect on ER+ and HER2+ breast cancer cells compared to petroleum ether or N-butanol extracts. APR inhibited ER+ and HER2+ breast cancer cell growth, proliferation, migration, and invasion via the phosphatidylinositol-3 kinase (PI3K)/AKT pathway. CONCLUSIONS: APR had a significant inhibitory effect on ER+ and HER2+ breast cancer cells via the PI3K/AKT signaling pathway. Therefore, APR may be useful for preventing ER+ and HER2+ breast tumor growth, proliferation, migration, and invasion.

Baicalein inhibits inflammatory response and promotes osteogenic activity in periodontal ligament cells challenged with lipopolysaccharides.

BACKGROUND: Periodontitis is a chronic infection initiated by oral bacterial and their virulence factors, yet the severity of periodontitis is largely determined by the dysregulated host immuno-inflammatory response. Baicalein is a flavonoid extracted from Scutellaria baicalensis with promising anti-inflammatory properties. This study aims to clarify the anti-inflammatory and osteogenic effects of baicalein in periodontal ligament cells (PDLCs) treated with lipopolysaccharides (LPS). METHODS: Human PDLCs were incubated with baicalein (0-100 µM) for 2 h prior to LPS challenge for 24 h. MTT analysis was adopted to assess the cytoxicity of baicalein. The mRNA and protein expression of inflammatory and osteogenic markers were measured by real-time polymerase chain reaction (PCR), western blot and enzyme-linked immunosorbent assay (ELISA) as appropriate. Alkaline phosphatase (ALP) and Alizarin red S (ARS) staining were performed to evaluate the osteogenic differentiation of PDLCs. The expression of Wnt/ß-catenin and mitogen-activated protein kinase (MAPK) signaling related proteins was assessed by western blot. RESULTS: MTT results showed that baicalein up to 100 µM had no cytotoxicity on PDLCs. Baicalein significantly attenuated the inflammatory factors induced by LPS, including interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), matrix metalloprotein-1 (MMP-1), MMP-2 and monocyte chemoattractant protein 1 (MCP-1) at both mRNA and protein level. Moreover, MAPK signaling (ERK, JNK and p38) was significantly inhibited by baicalein, which may account for the mitigated inflammatory response. Next, we found that baicalein effectively restored the osteogenic differentiation of LPS-treated PDLCs, as shown by the increased ALP and ARS staining. Accordingly, the protein and gene expression of osteogenic markers, namely runt-related transcription factor 2 (RUNX2), collagen-I, and osterix were markedly upregulated. Importantly, baicalein could function as the Wnt/ß-catenin signaling activator, which may lead to the increased osteoblastic differentiation of PDLCs. CONCLUSIONS: With the limitation of the study, we provide in vitro evidence that baicalein ameliorates inflammatory response and restores osteogenesis in PDLCs challenged with LPS, indicating its potential use as the host response modulator for the management of periodontitis.