Inhibitory Effects of Pectinase‐Treated Prunus Mume Fruit Concentrate on Colorectal Cancer Proliferation and Angiogenesis of Endothelial Cells

Abstract

Pectinase is a well‐known enzyme used in the food processing industry to produce fruit juice and concentrate. This study evaluated the anticancer and antiangiogenesis activities of pectinase‐treated Prunus mume fruit concentrate (PC) and its phenolic components. PC treatment (250 to 1,000 µg/mL) resulted in decreased proliferation of SW480 human colorectal cancer cells through S‐phase cell cycle arrest; however, equivalent concentrations of PC did not show toxicity toward CRL‐1539 colon normal cells. Furthermore, PC‐induced caspase‐dependent apoptosis in SW480 cells, which was characterized by accumulation of apoptotic cell population, cell shrinkage, formation of apoptotic bodies, upregulation of proapoptotic Bax, cleaved PARP, caspase‐3, caspase‐8, and caspase‐9, and downregulation of antiapoptotic Bcl‐2. Antiangiogenesis effects of PC were assessed using human umbilical vein endothelial cells (HUVECs). We found that PC did not inhibit HUVECs proliferation at concentrations of 500 to 1,500 µg/mL. In addition, treatment with PC at nontoxic concentrations (500 to 1,000 µg/mL) blocked vascular endothelial growth factor induced cell migration, invasion, capillary‐like tube formation, and angiogenesis from rat aortic rings. HPLC‐PDA analysis showed that there were at least four different phenolics including 5‐HMF, neochlorogenic acid, protocatechuic acid, and syringic acid. Taken together, these results indicated that PC could be used as a good source of phenolic compounds with selective anticancer and antiangiogenesis activities. Practical Application Pectinases are one of the well‐known enzyme used in the part of food processing. Treatment of pectinase is a useful strategy to reduce viscosity, turbidity, and pulp particles in the production of fruit juice, extract, and concentrate. In the present study, we found that pectinase‐treated P. mume fruit concentrate significantly suppresses colorectal cancer proliferation and angiogenesis of human umbilical vein endothelial cells. The significance of our findings is that pectinase‐treated P. mume concentrate may be used as a commercial functional food material to inhibit colorectal cancer and angiogenesis.

Comprehensive Review of Phytochemical Constituents, Pharmacological Properties, and Clinical Applications of Prunus mume

“…The antitumor effects of P. mume have been an important focus of pharmacological studies of the plant in recent years. MK615 and other compounds extracted from P. mume have exhibited anti-proliferative activity in vitro on many human cancer cell lines (Jeong et al, 2006), for example, the human hepatocellular carcinoma cell lines HuH7, HepG2, and Hep3B (Okada et al, 2007;Sakuraoka et al, 2010); human colon cancer cell lines SW480, COLO, and WiDr (Mori et al, 2007;Cho et al, 2019); human pancreatic cancer cell lines PANC-1, PK-1, PK45H, and MIAPaCa-2 cells (Toshie, 2008;Hattori et al, 2013); human malignant melanoma cell lines SK-MEL28 and A375 cells (Tada et al, 2012); human breast cancer cell lines MDA-MB-468 and MCF-7 cells (Nakagawa et al, 2007); human lung cancer cell lines A549 and PC14 cells (Sunage et al, 2011); and human leukemia cell lines HIMeg, HL-60, and Su9T01 cells (Shen et al, 1995;Kai et al, 2011). The proposed antitumor mechanisms, involved directly suppressing Aurora A and Aurora B kinase activity, inhibition of NF-κB activation (Toshie, 2008), triggering of apoptosis and autophagy (Mori et al, 2007), inducing accumulation of ROS in cancer cells but not in normal endothelial cells (Hattori et al, 2013), inhibition of the ERK1/2 and DNA binding-1 (Id-1) pathways, decreasing Bcl-2 expression (Tada et al, 2012), and suppressing hypoxia tolerance by up-regulation of E-cadherin in cancer cells with mutant KRAS (Nishi et al, 2020).…”

“…To date, phytochemical studies have discovered numerous chemical components of the plant, mainly phenolics (Xia et al, 2011;Mitani et al, 2013), flavonoids (Yan et al, 2014a), and organic acids (Gao, 2012). Modern pharmacological studies have disclosed various biological activities and bioactive mechanisms of P. mume and its formulas, including antidiabetic (Kishida et al, 2013;Ko et al, 2013), hepatoprotective (Hokari, 2012;Beretta et al, 2016), antitumoral (Hattori et al, 2013;Cho et al, 2019), antiinflammatory (Morimoto et al, 2009;Mitani et al, 2013), and antimicrobial (Lee and Stein, 2011;Seneviratne et al, 2011) activities. Bailly (2020) reviewed anticancer properties of P. mume extracts, however, no comprehensive review on the phytochemical and pharmacological properties of P. mume is available.…”

Alternative Options for Skin Cancer Therapy via Regulation of AKT and Related Signaling Pathways

“…The active compound 4-hydroxy-3,5-dimethoxybenzoic acid is derived from Euterpe oleracea and Rhus javanica extract, and inhibits colorectal cancer and oral squamous cell carcinoma [ 46 , 47 ]. Syringic acid (0.2 and 1 mM) prevented UVB (0.2 J/cm 2 )-induced skin papilloma and tumors in SKH-1 hairless mice [ 48 ].…”

Screening and Molecular Identification of Novel Pectinolytic Bacteria from Forest Soil

“…Moreover, pectinases are applied for bioethanol production, liquefaction and saccharification of biomass, bio-scouring of cotton fiber, retting and degumming plant fiber, and oil extraction [3][4][5]. A recent study also showed that pectinase-treated fruit juice has inhibitory effects on colorectal cancer proliferation [6]. Due to the extensive applications of pectinase in different avenues, the demand for pectinase enzymes is increasing continuously [7].…”