Riparsaponin isolated from Homonoia?riparia Lour induces apoptosis of oral cancer cells

Abstract

Abstract. Homonoia riparia Lour (Euphorbiaceae) is a known source of herbal medicine in China, and riparsaponin (RSP) is an active constituent isolated from H. riparia. The aim of the present study was to investigate the antitumor effect of RSP on human oral carcinoma cells and its potential underlying molecular mechanism. RSP was isolated from roots of H. riparia and identified using nuclear magnetic resonance. An MTT assay was used to evaluate the cytotoxicity of RSP on human oral carcinoma cells. Subsequently, DAPI staining was performed to investigate the apoptotic effect of RSP. To investigate the potential underlying molecular mechanism of action of RSP, western blotting was performed to determine the expression of cleaved caspase 3/9, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), Bcl-2-associated death promoter (Bad), epithelial cadherin (E-CAD), c-MET, matrix metalloproteinase (MMP)-2 and MMP-9. RSP exhibited a significant anti-proliferative effect on oral carcinoma cells at concentrations between 10 and 200 µg/ml via apoptosis. Following treatment with RSP (20, 40 and 80 µg/ml), expression of cleaved caspase-3 (P<0.05, P<0.01 and P<0.01, respectively), cleaved caspase-9 (P<0.01), Bad (P<0.01), Bax (P<0.01), c-MET (P<0.01), MMP-2 (P<0.01) and MMP-9 (P<0.01) in oral carcinoma cells was increased significantly compared with the control group, whereas expression of Bcl-2 (P<0.01) and E-CAD (P<0.01) was decreased. These results suggest that RSP possessed notable antitumor activity against oral squamous cell carcinoma by inducing mitochondria-mediated apoptosis. IntroductionIt is reported that oral squamous cell carcinoma (OSCC), one of the most common oral malignancies of the squamous epithelium of the oral cavity, is the sixth most common type of cancer globally (1-3). It has been reported that developing countries have the highest incidence rates of OSCC and it is expected that the incidence will continue to increase (4); furthermore, OSCC commonly occurs in middle-aged and elderly males because of tobacco and alcohol use (5). OSCC commonly occurs in the tissues of the oral cavity, including the gingiva, tongue, lip, hard palate, buccal mucosa and mouth floor (4,6). OSCC exhibits a marked propensity for invasive growth and metastasis, leading to damage of the original tissues or that of distant organs (2,4). The predominant treatment strategy for OSCC is radical surgery and postoperative chemoradiation (4). Marked improvements have been made in clinical diagnosis and management of OSCC; however, high recurrence rates and low 5-year survival rates have remained constant for several decades (7).Increasingly, previous studies have revealed that chemotherapy using natural agents with low toxicity is a promising approach for treating various types of cancer (8-10). In addition, traditional Chinese medicine (TCM) has been used in the treatment of various incurable diseases for centuries, and the reliability and effectiveness of TCMs have been demonstrated by long-term clinical use in China (11,12)...

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“…Staining treated cancer cells and their examination via fluorescent microscopy are considered as acceptable methods for the evaluation of morphological changes as well as cytotoxicity expression in the chromatin and cell membrane (Li & Wang et al., 2017). The DAPI staining method was engaged to detect the phenotypic sign of apoptosis in treated cancerous cells.…”

Assessing the protective effects of cryptotanshinone on CoCl2‑induced hypoxia in RPE cells

“…HIF-1α is hydroxylated by prolyl hydroxylase under conditions of sufficient oxygen, leading to its degradation. However, under hypoxic conditions, the HIF-1α protein is stabilized and accumulates due to inhibition of prolyl hydroxylase ( 26 ). The hydroxylation of prolyl hydroxylase requires molecular oxygen, and cobalt can replace the ferrous ions bound to the active site, causing the inactivation of hydroxylase, thereby stabilizing the HIF-1α protein, and this has been widely used to simulate hypoxia in vitro ( 27 ).…”

“…Cytochrome c is an initiator of apoptosis, and is primarily associated with the Bcl-2 family of proteins, such as Bax and Bcl-2. Bax promotes the release of cytochrome c from the mitochondria, thereby activating a series of downstream caspase reactions leading to apoptosis, whereas Bcl-2 prevents the release of cytochrome C by maintaining the integrity of the mitochondrial membrane ( 26 , 28 ).…”

Advances in Small Molecular Agents against Oral Cancer

“…In addition, ginsenoside M1 (64) dose-dependently inhibits the colony formation and migration of SAS and OEC-M1 cells and reduces the expression of the transfer-related protein vimentin. Li et al [100] found that riparsaponin (65) inhibits OSCC metastasis by down-regulating the expression of cellular-mesenchymal epithelial transition factor (c-MET), MMP-2, and MMP-9 and by up-regulating the expression of E-cadherin; it also shows significant anti-OSCC activity by inducing mitochondria-mediated apoptosis. Gambogic acid causes the G1 arrest of OSCC cells.…”