ScopeThis study aims to investigate the anticancer properties of Citrus grandis ‘Tomentosa’ (CGT) in non‐small cell lung cancer (NSCLC).Methods and resultsThe ethanol extract of CGT (CGTE) is prepared by using anhydrous ethanol and analyzed by ultra‐performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS), revealing that the main chemical components in CGTE are flavonoids and coumarins, such as naringin, rhoifolin, apigenin, bergaptol, and osthole. CGTE at concentrations without inducing cell death significantly inhibits cell proliferation via inducing cell cycle G1 phase arrest by MTT, colony formation, and flow cytometry assays, implying that CGT has anticancer potential. CGTE markedly inhibits the activity of Skp2‐SCF E3 ubiquitin ligase, decreases the protein level of Skp2, and promotes the accumulation of p27 by co‐immunoprecipitation (co‐IP) and in vivo ubiquitination assay; whereas Skp2 overexpression rescues the effects of CGTE in NSCLC cells. In subcutaneous LLC allograft and A549 xenograft mouse models, CGTE, without causing obvious side effects in mice, significantly inhibits lung tumor growth by targeting the Skp2/p27 signaling pathway.ConclusionThese findings demonstrate that CGTE efficiently inhibits NSCLC proliferation both in vitro and in vivo by targeting the Skp2/p27 signaling pathway, suggesting that CGTE may serve as a therapeutic candidate for NSCLC treatment.

Activation of inflammasomes has been reported in human pancreatic adenocarcinoma (PAAD); however, the expression pattern and functional role of inflammasome-related proteins in PAAD have yet to be identified. In this study, we systemically examined the expression and role of different inflammasome proteins by retrieving human expression data. Several genes were found to be differentially expressed; however, only interferon-inducible protein 16 (IFI16) expression was found to be adversely correlated with the overall survival of PAAD patients. Overexpression of IFI16 significantly promoted tumor growth, increased tumor size and weight in the experimental PAAD model of mice, and specifically increased the population of tumor-associated macrophages (TAMs) in the tumor microenvironment. Depletion of TAMs by injection of liposome clodronate attenuated the IFI16 overexpression-induced tumor growth in PAAD. In vitro treatment of conditioned medium from IFI16-overexpressing PAAD cells induced maturation, proliferation, and migration of bone marrow-derived monocytes, suggesting that IFI16 overexpression resulted in cytokine secretion that favored the TAM population. Further analysis suggested that IFI16 overexpression activated inflammasomes, thereby increasing the release of IL-1β. Neutralization of IL-1β attenuated TAM maturation, proliferation, and migration induced by the conditioned medium from IFI16-overexpressing PAAD cells. Additionally, knockdown of IFI16 could significantly potentiate gemcitabine treatment in PAAD, which may be associated with the reduced infiltration of TAMs in the tumor microenvironment. The findings of our study shed light on the role of IFI16 as a potential therapeutic target for PAAD.

Cynanchum paniculatum Radix, known as Xuchangqing in Chinese, is commonly prescribed in Chinese Medicine (CM) for the treatment of various inflammatory diseases. The anti-inflammatory property of Cynanchum paniculatum can be traced from its wind-damp removing, collaterals’ obstruction relieving, and toxins counteracting effects as folk medicine in CM. This paper systematically reviewed the research advancement of the pharmacological effects of Cynanchum paniculatum among a variety of human diseases, including diseases of the respiratory, circulatory, digestive, urogenital, hematopoietic, endocrine and metabolomic, neurological, skeletal, and rheumatological systems and malignant diseases. This review aims to link the long history of clinical applications of Cynanchum paniculatum in CM with recent biomedical investigations. The major bioactive chemical compositions of Cynanchum paniculatum and their associated action mechanism unveiled by biomedical investigations as well as the present clinical applications and future perspectives are discussed. The major focuses of this review are on the diverse mechanisms of Cynanchum paniculatum and the role of its active components in inflammatory diseases.