Cytotoxic effect ofErythroxylum daphnitesextract is associated with G₁cell cycle arrest and apoptosis in oral squamous cell carcinoma

Abstract

Plant-derived molecules showing antineoplastic effects have recently gained increased attention as potential adjuvants to traditional therapies for various cancers. Cerrado biome in Brazil contains high floral biodiversity, but knowledge about the potential therapeutic effects of compounds derived from that flora is still limited. The present study investigated the antineoplastic activity of Erythroxylum daphnites Mart., a Brazilian native plant from Cerrado biome, in the SCC-9 oral squamous cell carcinoma cell line. Cells were treated with various concentrations of hexane extract of Erythroxylum daphnites leaves (EDH) and assessed for cytotoxicity, proliferation, and apoptosis. Thin layer chromatography was conducted to characterize the substances present in EDH. Our results showed that EDH exerted anti-proliferative effects in SCC-9 cells by stabilizing the cell cycle at G 1 phase in association with reduced intracellular levels of cyclins D and E and increased level of p21. EDH also demonstrated pro-apoptotic properties, as shown by an increased expression of caspase-3. Triterpenes were the major constituents of EDH. Our findings demonstrated a cytotoxic effect of EDH against SCC-9 cells in vitro mediated by the restraint of cellular proliferation and induction of apoptosis. Taken together, these findings support EDH constituents as potential therapeutic adjuvants for oral cancer.

Advances in chemistry and bioactivity of the genus Erythroxylum

“…8 ; Table 8 ), which include two acetophenone diglycosides ( 188–189 ) isolated from E. cambodianum [ 72 ], neochlorogenic acid ( 190 ) and protocatechuic acid ( 191 ) extracted from E. lucidum [ 68 ], and scoparon ( 192 ) yielded from E. barbatum [ 76 ]. Additionally, five steroids ( 193–197 ) have been identified in this genus according to the previous studies [ 35 , 44 , 46 – 48 , 76 , 77 ] (Fig. 8 ; Table 8 ).…”

“…5 ; Table 5 ). Besides, recent studies reported five triterpenes ( 92–96 ) from E. ovalifolium [ 14 ], E. daphnites [ 48 ] or E. macrocalyx [ 49 ]. Interestingly, all the triterpenoids identified in this genus are pentacyclic triterpenes.…”

“…Exploring and evaluating bioactivities of the numerous diterpenoids found in Erythroxylum species will be essential for further effective utilization of these natural product resources in this genus. For triterpenes, compounds 93–95 were major constituents of the hexane extract of E. daphnites leaves which showed a cytotoxic effect against SCC-9 oral squamous cell carcinoma cell line [ 48 ]. Additionally, sterols ( 193 , 194 ) isolated from E. monogynum possess good anti-oxidant and anti-glycation activities [ 77 ].…”

Scutellarin suppresses proliferation and increases apoptosis of nasopharyngeal carcinoma cells via MAPKs/NF-κB signaling pathway through G0/G1 cell cycle arrest – An in-vitro approach

“…It is well known that tumor cell apoptotic generation is a fundamental therapeutic approach for malignant treatment. [34] Modifications in the cell cycle may increase metabolism and affect viability. [35] Currently, we noticed that SL reduced cyclin-D1, CDK 4, CDK 6, and pRB expression levels.…”

Streptomyces sp. strain MUSC 5 from mangrove forest in Malaysia: Identification, antioxidant potential and chemical profiling of its methanolic extract

“…Both the ethanolic and water extract of propolis demonstrated antioxidant and antimicrobial activities and pentacosanoic acid, methyl ester (6) was confirmed in both extracts [87] . Hexacosanoic acid, methyl ester (7) was reported in a plant extract demonstrating anticancer properties [88] .…”