Qiang Xie

Bio: Qiang Xie is an academic researcher from University of Electronic Science and Technology of China. The author has contributed to research in topics: Histone methyltransferase & Targeted therapy. The author has co-authored 2 publications.

Targeting Autophagy with Natural Compounds in Cancer: A Renewed Perspective from Molecular Mechanisms to Targeted Therapy.

Abstract: Natural products are well-characterized to have pharmacological or biological activities that can be of therapeutic benefits for cancer therapy, which also provide an important source of inspiration for discovery of potential novel small-molecule drugs. In the past three decades, accumulating evidence has revealed that natural products can modulate a series of key autophagic signaling pathways and display therapeutic effects in different types of human cancers. In this review, we focus on summarizing some representative natural active compounds, mainly including curcumin, resveratrol, paclitaxel, Bufalin, and Ursolic acid that may ultimately trigger cancer cell death through the regulation of some key autophagic signaling pathways, such as RAS-RAF-MEK-ERK, PI3K-AKT-mTOR, AMPK, ULK1, Beclin-1, Atg5 and p53. Taken together, these inspiring findings would shed light on exploiting more natural compounds as candidate small-molecule drugs, by targeting the crucial pathways of autophagy for the future cancer therapy.

Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies

Abstract: Triple-negative breast cancer (TNBC) is a subtype of human breast cancer with one of the worst prognoses, with no targeted therapeutic strategies currently available. Regulated cell death (RCD), also known as programmed cell death (PCD), has been widely reported to have numerous links to the progression and therapy of many types of human cancer. Of note, RCD can be divided into numerous different subroutines, including autophagy-dependent cell death, apoptosis, mitotic catastrophe, necroptosis, ferroptosis, pyroptosis and anoikis. More recently, targeting the subroutines of RCD with small-molecule compounds has been emerging as a promising therapeutic strategy, which has rapidly progressed in the treatment of TNBC. Therefore, in this review, we focus on summarizing the molecular mechanisms of the above-mentioned seven major RCD subroutines related to TNBC and the latest progress of small-molecule compounds targeting different RCD subroutines. Moreover, we further discuss the combined strategies of one drug (e.g., narciclasine) or more drugs (e.g., torin-1 combined with chloroquine) to achieve the therapeutic potential on TNBC by regulating RCD subroutines. More importantly, we demonstrate several small-molecule compounds (e.g., ONC201 and NCT03733119) by targeting the subroutines of RCD in TNBC clinical trials. Taken together, these findings will provide a clue on illuminating more actionable low-hanging-fruit druggable targets and candidate small-molecule drugs for potential RCD-related TNBC therapies.

Estrogen Receptor Beta 1: A Potential Therapeutic Target for Female Triple Negative Breast Cancer.

Abstract: Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer characterized by the absence of estrogen receptor alpha, progesterone receptor, and HER2. These receptors often serve as targets in breast cancer treatment. As a result, TNBCs are difficult to treat and have a high propensity to metastasize to distant organs. For these reasons, TNBCs are responsible for over 50% of all breast cancer mortalities while only accounting for 15% - 20% of breast cancer cases. However, estrogen receptor beta 1 (ERβ1), an isoform of the ESR2 gene, has emerged as a potential therapeutic target in the treatment of TNBCs. Using an in vivo xenograft preclinical mouse model with human TNBC, we found that expression of ERβ1 significantly reduced both primary tumor growth and metastasis. Moreover, TNBCs with elevated levels of ERβ1 showed reduction in epithelial-to-mesenchymal transition (EMT) markers and breast cancer stem cell (BCSC) markers, and increases in the expression of genes associated with inhibition of cancer cell invasiveness and metastasis, suggesting possible mechanisms underlying the antitumor activity of ERβ1. Gene expression analysis by qPCR and RNA-seq revealed that treatment with CLI, an ERβ selective agonist ligand often enhanced the suppressive activity of ERβ1 in TNBCs in vivo or in TNBC cells in culture, suggesting the potential utility of ERβ1 and ERβ ligand in improving TNBC treatment. The findings enable understanding of the mechanisms by which ERβ1 impedes TNBC growth, invasiveness and metastasis and consideration of ways by which treatments involving ERβ might improve TNBC patient outcome.

Screening of Apoptosis Pathway-Mediated Anti-Proliferative Activity of the Phytochemical Compound Furanodienone against Human Non-Small Lung Cancer A-549 Cells

Abstract: Furanodienone (FDN), a major bioactive component of sesquiterpenes produced from Rhizoma Curcumae, has been repeatedly acknowledged for its intrinsic anticancer efficacy against different types of cancer. In this study, we aimed to investigate the cytotoxic potential of furanodienone against human lung cancer (NSCLC A549) cells in vitro, as well as its underlying molecular mechanisms in the induction of apoptosis. Herein, we found that FDN significantly inhibited the proliferation of A549 cells in a dose-dependent manner. In addition, treatment with FDN potentially triggered apoptosis in A549 cells via not only disrupting the nuclear morphology, but by activating capsase-9 and caspase-3 with concomitant modulation of the pro- and antiapoptotic gene expression as well. Furthermore, FDN revealed its competence in inducing cell cycle arrest at G0/G1 phase in A549 cells, which was associated with decreased expression of cyclin D1 and cyclin-dependent kinase 4 (CDK4), along with increased expression of CDK inhibitor p21Cip1. Intriguingly, FDN treatment efficiently downregulated the Wnt signaling pathway, which was correlated with increased apoptosis, as well as cell cycle arrest, in A549 cells. Collectively, FDN might represent a promising adjuvant therapy for the management of lung cancer.