cytochrome-c-t and hyperoside

Hyperoside (HY) is a major pharmacologically active component from Prunella vulgaris L. and Hypericum perforatum. The present study aimed to determine the anticancer effect of HY and determine the underlying mechanisms involved. Human A549 cells were treated with HY (10, 50 and 100 µM), and cell viability was detected by an MTT assay. Cell apoptosis and mitochondrial membrane potential were determined by flow cytometry. Western blot analysis was used to identify the expression of apoptosis‑associated proteins and phosphorylation of MAPK. The present study demonstrated that HY significantly inhibited the viability of A549 cells in a time‑ and dose‑dependent manner, and enhanced the percentage of apoptotic cells. HY also significantly increased the protein phosphorylation of p38 mitogen‑activated protein kinase (MAPK) and c‑Jun N‑terminal kinase (JNK), disrupted mitochondrial membrane penetrability, and triggered the release of mitochondrial cytochrome c and apoptosis‑inducing factor into the cytosol. Treatment with HY also activated the expression of caspase‑9 and caspase‑3. These results suggested that HY‑induced apoptosis was associated with activation of the p38 MAPK‑ and JNK‑induced mitochondrial death pathway. HY may offer potential for clinical applications in treating human non‑small cell lung cancer and improving cancer chemotherapy.

Topics: A549 Cells; Antineoplastic Agents, Phytogenic; Apoptosis; Caspase 3; Caspase 9; Cell Fractionation; Cell Survival; Cytochromes c; Cytosol; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Humans; JNK Mitogen-Activated Protein Kinases; Membrane Potential, Mitochondrial; Mitochondria; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Quercetin; Signal Transduction

The present study aimed to demonstrate the antiproliferative effect of hyperoside from Zanthoxylum bungeanum leaves (HZL) and explain the underlying molecular mechanisms in the SW620 human colorectal cancer cell line. The cytotoxic effects of HZL were determined using a3‑(4,5‑dimethylthiazol‑2‑yl)2,5‑diphenyltetrazolium bromide assay. Apoptosis and cell cycle were detected using flow cytometry. Reactive oxygen species (ROS) levels and mitochondrial membrane potential (∆Ψm) were assessed using 2',7'‑dichlorofluorescin diacetate and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl carbocyanine iodide fluorescence spectrophotometry, respectively. Western blot analysis was used to quantify the expression levels of apoptosis‑associated proteins. Reverse transcription‑quantitative polymerase chain reaction analysis was used to determine the mRNA expression of glutathione peroxidase (GSH‑Px) and catalase (CAT). HZL had a marked anti‑proliferative effect on the SW620 human colorectal cancer cells by inducing cell cycle G2/M phase arrest and apoptosis, which was associated with an increase in the expression of p53 and p21. Further mechanistic investigations revealed that the induction of apoptosis was associated with increased generation of ROS, reduced ∆Ψm, and upregulation of B‑cell lymphoma 2‑associated X protein, cytochrome c, caspase‑9, apoptotic protease activating factor 1 and caspase‑3. The antitumor potency of HZL was also attributed to inhibition of the mRNA expression levels of GSH‑Px and CAT. These data indicated that HZL may be involved in the pro‑apoptotic signaling of SW620 human colorectal cancer cells via induction of the caspase‑dependent apoptosis and p53 signaling pathways.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Catalase; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Cyclin-Dependent Kinase Inhibitor p21; Cytochromes c; G2 Phase Cell Cycle Checkpoints; Glutathione Peroxidase; Humans; M Phase Cell Cycle Checkpoints; Membrane Potential, Mitochondrial; Plant Leaves; Quercetin; Reactive Oxygen Species; Signal Transduction; Tumor Suppressor Protein p53; Up-Regulation; Zanthoxylum