Inhibition of nasopharyngeal carcinoma cell proliferation and synergism of cisplatin with silvestrol and episilvestrol isolated from Aglaia stellatopilosa

Abstract

Nasopharyngeal carcinoma (NPC) is a type of tumour that arises from the epithelial cells that line the surface of the nasopharynx. NPC is treated with radiotherapy and cytotoxic chemotherapeutic drugs such as cisplatin and 5-fluorouracil. However, current strategies are often associated with potential toxicities. This has prompted efforts to identify alternative methods of treatment. The present study aimed to investigate silvestrol and episilvestrol-mediated inhibition of cell proliferation in human NPC cells. The growth kinetics of NPC cells treated with silvestrol or episilvestrol were monitored dynamically using a real-time, impedance-based cell analyzer, and dose-response profiles were generated using a colorimetric cell viability assay. Furthermore, apoptosis was evaluated using flow cytometry and high content analysis. In addition, flow cytometry was performed to determine cell cycle distribution. Finally, the effects of combining silvestrol or episilvestrol with cisplatin on NPC cells was examined. Apoptosis was not observed in silvestrol and episilvestrol-treated NPC cells, although cell cycle perturbation was evident. Treatment with both compounds induced a significant increase in the percentage of cells in the G2/M phase, as compared with the control. In vitro cultures combining silvestrol or episilvestrol with cisplatin showed synergistic effects against NPC cells. The results of the present study suggested that silvestrol and episilvestrol had an anti-tumour activity in NPC cells. Silvestrol and episilvestrol, particularly in combination with cisplatin, merit further investigation, so as to determine the cellular mechanisms underlying their action(s) as anti-NPC agents.

Localised Delivery of Cisplatin from Chitosan-Coated Titania Nanotube Array Nanosystems Targeting Nasopharyngeal Carcinoma

“… 26 The C666-1, an EBV-related NPPC was more susceptible to the chemotherapeutic drug treatment, resulting in a lower IC 50 of CDDP-treated cells. In comparison to C666-1, the resistance of NPC/HK-1 towards CDDP treatment was previously noted by Daker et al 27 In the same report, Daker also discussed on the higher sensitivity of C666-1 compared to NPC/HK-1 towards the NPC treatment given thus confirming the resistance of NPC/HK-1 towards cancer treatment. Earlier reports also discussed the importance of using other chemotherapeutic drugs, such as the combination of CDDP and 5-fluorouracil, to treat NPC/HK-1 effectively.…”

“…Earlier reports also discussed the importance of using other chemotherapeutic drugs, such as the combination of CDDP and 5-fluorouracil, to treat NPC/HK-1 effectively. 27 , 28 However, according to Low et al, 29 undifferentiated C666-1 appears to be less sensitive towards CDDP treatment compared with differentiated NPC/HK-1. This phenomenon could be explained by the involvement of DUSP16 in the response of NPC towards CDDP treatment.…”

Analysis of NK-92 cytotoxicity in nasopharyngeal carcinoma cell lines and patient-derived xenografts using impedance-based growth method

“…Following this, cytotoxicity results obtained by xCELLigence were similar to conventional MTT assay. In NPC studies, xCELLigence was commonly used to monitor cellular processes such as proliferation, migration and invasion [ [35] , [36] , [37] ]. A recent immunotherapy publication used xCELLigence to detect cytotoxicity effect of Epstein-Barr virus latent membrane protein 2 (EBV LMP2)-activated CD8 + T cells against LMP2-expressing target cells [ 38 ].…”

Comparative phytochemistry of flavaglines (= rocaglamides), a group of highly bioactive flavolignans from Aglaia species (Meliaceae)

“…5). Synergistic effects of compounds 14 and 15 in combination with cisplatin were observed in the inhibition of nasopharyngeal carcinoma cell proliferation (Daker et al 2016). Recently, both silvestrols (14, 15) were also isolated from the stems of A. stellatopilosa Pannell and their strong cytotoxicity was confirmed against the cancer cell lines H-29, MCF-7, and NCI-H460 (Othman et al 2016).…”