Inhibitory effect of hyperoside isolated from Zanthoxylum bungeanum leaves on SW620 human colorectal cancer cells via induction of the p53 signaling pathway and apoptosis

Abstract

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.

Hyperoside Induces Breast Cancer Cells Apoptosis via ROS-Mediated NF-κB Signaling Pathway

“…The biofunctions of hyperoside were mainly involved in antioxidants, hypoglycemic, anti-cancer, anti-inflammatory and cardiovascular effects [19]. Previous studies have showed that hyperoside can help with the amelioration of lung cancer [20], pancreatic cancer [21], prostate cancer [22] and colon cancer [23]. However, whether hyperoside has therapeutic effects on breast cancer remains elusive.…”

Simultaneous Enrichment and Separation of Four Flavonoids from Zanthoxylum bungeanum Leaves by Ultrasound‐Assisted Extraction and Macroporous Resins with Evaluation of Antioxidant Activities

“…In our previous studies, according to the results of the structure–activity relationship of nine flavonoids from Z. bungeanum leaves (Zhang, Wang, Yang, Zhou, & Zhang, ) and the correlation between the chromatographic fingerprint and antioxidant activity of the 22 subsequent fractions of Z. bungeanum leaves ethanol extracts (Zhang, Luo, Wang, He, & Li, ; Zhang, Luo, & Wang, ), it was found that quercitrin, hyperoside, rutin, and afzelin were the dominant flavonoids, which played a major role in antioxidant and antimicrobial activity. Furthermore, hyperoside from Z. bungeanum leaves also exerts many bioactivities, such as antiproliferative effects against SW620 (Zhang, Dong, Zhang, & Zhang, ) and antihyperglycemic and hepatocyte‐protective effects (Zhang, Wang, Dong, Yu, & Zhang, ). Therefore, in view of these benefits, it is necessary to establish a simple, low‐cost and efficient purification method for the four flavonoids from Z. bungeanum leaves.…”

Comparison of tumor related signaling pathways with known compounds to determine potential agents for lung adenocarcinoma

“…It is interesting to discover that five classical signaling pathways play pivotal roles in the tumorigenesis of LUAD and can be targeted by known compounds. These five pathways, including pathways in cancer, and chemokine, MAPK, p53, and Fc epsilon RI signaling pathways, have been studied in multiple cancers, including LUAD . After analyzing these five pathways in CMap, several known compounds were identified.…”