Aloperine executes antitumor effects through the induction of apoptosis and cell cycle arrest in prostate cancer in vitro and in vivo

Abstract

BackgroundProstate cancer (PCa) is one of the most common malignant diseases among male patients. Although androgen deprivation therapy remains the main treatment for PCa, most patients would inevitably progress to castration-resistant PCa, which is the main cause of cancer-related deaths. Thus, novel antitumor agents are urgently needed. Recent studies demonstrated that aloperine (ALO) as a natural alkaloid showed antitumor effects in other cancer types. However, the biological function and underlying mechanisms of ALO in PCa have not been investigated.MethodsPCa cell lines including LNCaP, PC3 and DU145 were cultured and treated with ALO. Cell Counting Kit-8 assay, colony formation assay, apoptosis assay and cell cycle assay were conducted to assess the biological role of ALO. In addition, a PCa subcutaneous xenograft mouse model was established to evaluate the role of ALO in terms of proliferation and apoptosis in vivo. We further measured the protein expression levels of p-Akt/Akt, p-ERK/ERK, c-Myc, cleaved caspase 3, p21, p53, Bcl-2 and Bax using the Western blot 48 h after ALO treatment of PCa cells.ResultsALO effectively inhibited the cell viability of PCa by inducing cell cycle arrest via the activation of the p53/p21 pathway and triggering apoptosis in vitro and in vivo. ALO also inhibited phosphorylation of Akt and ERK protein kinases and activated cleaved caspase 3 while exerting antiproliferation function through inducing apoptosis and cell cycle arrest in PCa cells.ConclusionBased on our findings, we conclude that ALO could suppress the tumor growth and promote cell apoptosis and cell cycle arrest in PCa cells, which indicated that ALO could act as a novel therapeutic agent in treatment of human PCa.

Aloperine prevents hypoxia-induced epithelial-mesenchymal transition in bladder cancer cells through regulating the mTOR/p70S6K/4E-BP1 pathway

“…ALO inhibits proliferation, migration and invasion and induces apoptosis in human breast cancer cells [24]. ALO executes anti-tumor effects on prostate cancer through the induction of apoptosis and cell cycle arrest both in vitro and in vivo [15]. Our results showed that ALO inhibited the viability of bladder cancer cells cultured in hypoxia.…”

“…Therefore, increasing experiments have confirmed the therapeutic potential of ALO in many kinds of diseases. Notably, ALO has been demonstrated to have therapeutic potential in various cancers, including thyroid cancer, breast cancer, prostate cancer, myeloma, hepatocellular carcinoma, glioma, and colon cancer [13,[15][16][17][18].…”

miR‑590‑5p may regulate colorectal cancer cell viability and migration by targeting PDCD4

“…Previous studies have revealed that miRNAs may negatively regulate gene expression by binding to the 3'-untranslated region (UTR) of target mRNAs to silence gene expression (9)(10)(11). It has been widely established that miRNAs serve critical roles in the regulation of several biological process, including proliferation, differentiation, apoptosis, tumorigenesis and metastasis (6,12,13). Furthermore, miRNAs may predict overall prognosis in certain types of cancer, including lung cancer (14), gastric cancer (15) and CRC (16).…”

Network Pharmacology‐Based Analysis of the Pharmacological Mechanisms of Aloperine on Cardiovascular Disease

“…Aloperine is extracted from the traditional Chinese medicine Sophora alopecuroides L., which possesses a variety of pharmacological activities such as anti-inflammatory, antifibrosis, anticancer, and antimicrobial [5]. Aloperine executes antitumor effects through the induction of apoptosis and cell cycle arrest in vitro and in vivo [6,7].…”