neobavaisoflavone and Lung-Neoplasms

Neobavaisoflavone (Neo), as a traditional Chinese medicine, is the active ingredient in the herb Psoralea corylifolial and has antitumor activity. Myeloid-derived suppressor cells (MDSCs), which are a heterogeneous population of haematopoietic cells of the myeloid lineage, have been reported to be closely related to the pathogenesis of tumour progression, but whether Neo can regulate MDSC expansion and function remains unclear. Here, we found that Neo could inhibit the expansion and suppressive function of MDSCs by targeting STAT3. Importantly, Neo inhibited the growth of 4T1 and LLC tumours in vivo, as well as lung metastasis of 4T1 tumours in vivo. Furthermore, we identified MDSCs as the direct targets by which Neo attenuated tumour progression. In addition, Neo notably enhanced anti-PD-1 efficacy in anti-PD-1-insensitive 4T1 tumours. Therefore, our study sheds light on the development of Neobased therapeutic strategies against cancer.

Topics: Humans; Immunosuppression Therapy; Isoflavones; Lung Neoplasms; Myeloid-Derived Suppressor Cells

Lung cancer is the most commonly occurring cancer, which contributes to the majority of death caused by cancer, where non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer. To treat NSCLC, STAT3 has been identified as a target with therapeutic potential. The neobavaisoflavone (NBIF) is one of the flavonoids of traditional Chinese medicine Psoralea corylifolial.. Human NSCLC cell lines, PC-9, H460, and A549, were applied to determine NBIF's anti-proliferative effects through cell viability and colony formation detection. The effect of NBIF on cell apoptosis was determined through flow cytometry-based assay. Western blotting was used in this study to confirm the levels of P-STAT3, Bcl-2, and Bax, which are apoptotic proteins.. It was observed that NBIF could decrease the cell viability and its migration and induce apoptosis in human NSCLC cell lines dose-dependently. Levels of P-STAT3, as well as the downstream signals of the STAT3 pathway, were downregulated, suggesting that the tumorsuppression effects of NBIF might be related to the inhibition of STAT3 signaling. Furthermore, NBIF could contribute to the upregulation of BAX and downregulation of BCL2.. NBIF might perform the anti-NSCLC efficacy as a result of the inhibition of the STAT3 pathway. Besides, our work suggests that NBIF could provide therapeutic alternatives for NSCLC.

Topics: Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Humans; Isoflavones; Lung Neoplasms; STAT3 Transcription Factor

It is necessary to create novel, efficacious and harmless therapeutic strategy for lung cancer treatment. The application of nanoemulsion to specifically suppress cancer progression in the tumor microenvironment would be an effective therapy. Neobavaisoflavone (Neo) is an isoflavone isolated from Psoralea corylifolia L, possesses striking anti-inflammatory and anti-cancer effects. In our stduy, Neo significantly reduced reactive oxygen species (ROS) generation in the activated myofibroblast. Furthermore, a novel Neo nanoemulsion (nano-Neo) was prepared to improve Neo solubility and bioavailability. Nano-Neo showed more effectively anti-proliferative role in lung cancer cells. In addition, in vivo analysis further demonstrated that nano-Neo could effectively suppress tumor growth compared to the free Neo-treated mice without noticeable damage to major organs. Furthermore, nano-Neo treatment markedly reduced extracellular matrix (ECM) deposition in tumor samples by repressing transforming growth factor-β (TGF-β)/SMADs signaling pathway. Meanwhile, the activated immune microenvironment in tumor tissues was dramatically improved by nano-Neo through reducing regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) infiltration, as well as improving the count of natural killer (NK) cells and M2 macrophage phenotype switch to pro-inflammatory M1. In addition, we found that the prepared nano-Neo exerted promising tumor targeting efficiency with improved pharmacokinetic properties. Therefore, the novel approach to prepare nano-Neo introduced here might provide an effective strategy for lung cancer treatment with few adverse effects.

Topics: 3T3 Cells; A549 Cells; Animals; Antineoplastic Agents, Phytogenic; Cell Proliferation; Drug Compounding; Emulsions; Extracellular Matrix; Humans; Isoflavones; Lung Neoplasms; Lymphocytes, Tumor-Infiltrating; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Rats, Sprague-Dawley; Signal Transduction; Tumor Burden; Tumor Microenvironment; Tumor-Associated Macrophages; Xenograft Model Antitumor Assays