Chinese medicine formula 'Baipuhuang Keli' inhibits triple-negative breast cancer by hindering DNA damage repair via MAPK/ERK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Baipuhuang Keli (BPH, constituted by Bai Tou Weng (Pulsatilla chinensis (Bunge) Regel), Pu Gong Ying (Taraxacum mongolicum Hand.-Mazz.), Huang Qin (Scutellaria baicalensis Georgi), Huang Bo (Phellodendron amurense Rupr.)) is a Chinese herbal formula with clearing heat and cooling blood, and removing toxin effects, which is suit for the case of breast cancer. AIM OF THE STUDY: Here, we aim to explore the effects of BPH on triple-negative breast cancer (TNBC) and its potential mechanisms. MATERIALS AND METHODS: In this study, cell viability assay, colony formation assay, soft agar assay, cell proliferation curve assay, and EdU assay were employed to determine the anti-proliferation effect induced by BPH. Cell cycle distribution was detected by flow cytometry. DNA damage in cells treated with BPH was indicated by comet assay, immunofluorescence, and Western Blot. Both the 4T1 orthotopic tumor model and the MDA-MB-231 subcutaneous tumor model were used to assess in vivo effect of BPH (312.5, and 625 mg/kg). The protein expression levels of the DNA damage response (DDR) pathway and the MAPK/ERK pathway were detected by Western Blot. RESULTS: Our results indicated that TNBC cells were more sensitive to BPH than mammary epithelial cells. Cell proliferation of TNBC cells was significantly inhibited by BPH in a dose-dependent manner. Moreover, BPH induced DNA damage in TNBC cells in a concentration and time-dependent manner. DDR of TNBC cells was inhibited by BPH. MAPK/ERK pathway was inhibited in cells treated with BPH, and DNA damage can be reversed while EGF was added to activate MAPK/ERK pathway. The 4T1 orthotopic tumor model and the MDA-MB-231 subcutaneous tumor model further confirmed that BPH inhibited TNBC proliferation via inhibition of DDR and MAPK/ERK pathway in vivo. CONCLUSIONS: Collectively, we proved that BPH is a potential anticancer Chinese herbal formula for TNBC in the manner of in vitro and in vivo experiments.

Metabolism and polarization regulation of macrophages in the tumor microenvironment.

The occurrence and development of tumors depend on the tumor microenvironment (TME), which consists of various types of cellular and acellular components. Tumor-associated macrophages (TAMs) are the most abundant stromal cell types in the TME. The competition for nutrients between tumor cells and macrophages leads to a limited supply of nutrients, such as glucose, lipids, and amino acids, to immune cells, which affects the differentiation and function of macrophages. Other factors in the TME, such as cytokines, chemokines, and immune checkpoints, also affect the polarization and function of macrophages. Remodeling the tumor microenvironment induces changes in macrophage nutrient uptake and polarization status, which enhance anti-tumor immunity and oxidative stress resistance and suppress immune escape. This review summarizes the influence factors on tumor progression and immune function under different conditions of macrophages. It also demonstrates the metabolic heterogeneity and phenotypic plasticity of macrophages, which provides novel strategies for anti-tumor treatment.

Autophagy in cancer: The cornerstone during glutamine deprivation.

Over the past two decades, researchers have revealed the crucial functions of glutamine in supporting the hyperproliferation state of cancer cells. Glutamine acts on maintaining high energy production, supporting redox status and amino acid homeostasis. Therefore, cancer cells exhibit excessive uptake of the extracellular glutamine, synthesize it in some cases, and recycle intracellular and extracellular proteins to provide an additional source of glutamine to satisfy the increasing glutamine demand. On the other hand, autophagy's role is still debated regarding tumor initiation and progression. However, most cancer cells urgently need autophagy to overcome the existential threats during glutamine restriction stress. Downstream to various stress pathways induced during such a condition, autophagy is considered an indispensable cytoprotective tool to maintain cell integrity and survival. However, the overactivation of the autophagy process is related to lethal consequences. This review summarized glutamine pathways to control autophagy and highlighted autophagy's primary activation pathways, and discussed the roles during glutamine deprivation.

A Secure Scheme for Distributed Consensus Estimation against Data Falsification in Heterogeneous Wireless Sensor Networks.

Heterogeneous wireless sensor networks (HWSNs) can achieve more tasks and prolong the network lifetime. However, they are vulnerable to attacks from the environment or malicious nodes. This paper is concerned with the issues of a consensus secure scheme in HWSNs consisting of two types of sensor nodes. Sensor nodes (SNs) have more computation power, while relay nodes (RNs) with low power can only transmit information for sensor nodes. To address the security issues of distributed estimation in HWSNs, we apply the heterogeneity of responsibilities between the two types of sensors and then propose a parameter adjusted-based consensus scheme (PACS) to mitigate the effect of the malicious node. Finally, the convergence property is proven to be guaranteed, and the simulation results validate the effectiveness and efficiency of PACS.