14-Thienyl Methylene Matrine (YYJ18), the Derivative from Matrine, Induces Apoptosis of Human Nasopharyngeal Carcinoma Cells by Targeting MAPK and PI3K/Akt Pathways &lt;b&gt;&lt;i&gt;in Vitro&lt;/i&gt;&lt;/b&gt;

Background: Matrine is a bioactive alkaloid that has a variety of pharmacological effects and is widely used in Chinese medicine. However, its effects on male reproduction are not well known. In this study, we aimed to investigate the in vitro toxicity of matrine on mature mouse sperm. Methods: Mouse cauda epididymal sperm were exposed to matrine (10-200 µM) in vitro. The viability, motility, capacitation, acrosome reaction and fertilization ability of the mouse sperm were examined. Furthermore, the intracellular calcium concentration ([Ca²⁺]_i), calcium (Catsper) and potassium (Ksper) currents, and phosphorylation of extracellular signal regulated kinases 1/2 (p-ERK1/2) of the sperm were analyzed. Results: After exposure to 100 µM or more of matrine, mouse cauda epididymal sperm exhibited a significant reduction in total motility, progressive motility, linear velocity and acrosome reaction rate induced by Ca²⁺ ionophore A23187. As a result, the fertilization ability of mouse sperm was remarkably decreased by matrine. Our data further demonstrated that matrine significantly reduced sperm [Ca²⁺]_i and [Ca²⁺]_i-related p-ERK1/2; however, both the CatSper and KSper currents, which are thought to interactively regulate Ca²⁺ influx in sperm, were not affected by matrine. Conclusion: Our findings indicate that matrine inhibits mouse sperm function by reducing sperm [Ca²⁺]_i and suppressing the phosphorylation of ERK1/2.

Section: Discussionsupporting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Matrine Inhibits Mouse Sperm Function by Reducing Sperm [Ca2+]i and Phospho-ERK1/2

Luo

Zou²,

He³

et al. 2015

“…Because apoptosis induction appears to be the most important property for candidate anticancer drug, the morphological observation was conducted to explore whether the cytotoxic effect was related with the apoptotic process [4][5][6]. Elevation of oxidative stress species (ROS) in excess of the buffering capacity designed to modulate ROS levels result in potentially cytotoxic effect [7].…”

Section: Introductionmentioning

confidence: 99%

Pectolinarigenin Suppresses the Tumor Growth in Nasopharyngeal Carcinoma

Wang

Cheng

Liu

et al. 2016

Background/Aims: Nasopharyngeal cancer (NPC) is one of the common human malignant diseases all over the world, and chemotherapy remains the main therapy for NPC. However, the survival and life quality of NPC patients are still very poor. Thus, novel and selective anti-tumor agents are pressingly needed. Our previous study identified pectolinarigenin as a novel effective anti-tumor drug candidate for NPC. In this study, we further investigated its anti-tumor activities and explored the potential molecular mechanism. Methods: NPC C666-1 cells were cultured and treated by pectolinarigenin. Cell proliferation assay, colony formation assay, Transwell assay and wound healing assay were conducted and cell apoptosis was detected by flow cytometry. Mitochondrial transmembrane potential and ROS were also observed. NPC subcutaneous xenograft mice model was established to evaluate the anti-tumor effect of pectolinarigenin in vivo. Results: We observed that treatment of pectolinarigenin inhibited cell viability and cell migration of NPC C666-1 cells in concentration- and time-dependent manner. Pectolinarigenin induced cell apoptosis in C666-1 cells detected by flow cytometry analysis, which was associated with the activation of mitochondrial-related apoptosis and the accumulation of reactive oxygen species (ROS). Pectolinarigenin also activated caspase signaling pathway. The in vivo experiment of subcutaneous xenograft mice model also indicated that the administration of pectolinarigenin could decrease the tumor growth of NPC and no severe toxicity was observed. Conclusions: Based on our findings, we conclude that pectolinarigenin could suppress the tumor growth of NPC, which verifies it as a new therapeutic agent for treating this devastating disease.

“…The prevalence of NPC is low in most parts of the world, whereas it is high in southern China and other Southeast Asian Qi et [2]. Despite significant advancements in the treatment of NPC, the average 5-year survival rate remains between 34% and 52% [3].…”

Section: Introductionmentioning

confidence: 99%

MiR-142-3p Suppresses SOCS6 Expression and Promotes Cell Proliferation in Nasopharyngeal Carcinoma

Zhou

et al. 2015

Background/Aims: An increasing number of studies show that microRNAs (miRNAs) play crucial roles in nasopharyngeal carcinoma (NPC) tumorigenesis. The aim of our study was to investigate the biological roles and mechanisms of miR-142-3p in NPC. Methods: miR-142-3p expression was examined in NPC specimens and nasopharyngitis biopsy samples by quantitative real-time PCR. The biological functions of miR-142-3p were studied using a series of in vitro and in vivo approaches. Results: miR-142-3p is over-expressed in NPC tissues and cell lines. Knockdown of miR-142-3p significantly inhibited cell proliferation and cell cycle progression in vitro, and suppressed tumor growth in a mouse model. Suppressor of cytokine signaling 6 (SOCS6) was identified as a direct target of miR-142-3p, and miR-142-3p down-regulated the expression of SOCS6 by directly binding to its 3′untranslated region (UTR). Knockdown of SOCS6 abrogated the effects of miR-142-3p down-regulation. Conclusion: These findings indicate that miR-142-3p regulates NPC development by downregulating SOCS6 expression and suggest that modulation of miR-142-3p expression could be a therapeutic strategy for NPC.