Abstract
16-hydroxycleroda-3, 13-dine-15, 16-olide (HCD) isolated from Polyalthia longifolia possesses numerous biological activities. Previous studies have reported that HCD can block phosphorylation activity of cancer cells to inhibit tumor cell growth, but the anti-tumor activity in oral squamous cell carcinoma is unrevealed. This study investigates the inhibiting effect of HCD on human OSCC cell growth; thereby, developing a new oral cancer drug. In in vitro cultured human OSCC cells (OECM1 and SAS) were employed to test the inhibitory growth of HCD via cell cytotoxic effect using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, Western blotting, and further determining of the inhibitory efficacy of tumor growth by a xenograft tumor on BALB/c male nude mice (in vivo test). Under various concentrations of HCD and time course treatments were shown to effectively cause cell death and cell-cycle arrest in OECM1 and SAS cells, which was confirmed via a clinical drug (cisplatin) as a positive control. In addition, HCD induced the autophagic cell death in OECM1 and SAS cells by LC3-mediated LC3-I/LC3-II/p62 pathway at the in vitro level. An in vivo assay indicated that HCD could treat oral cancer by deferring tumor growth. These findings provide a favorable assessment for further elucidating the role of HCD that targets autophagic cell death pathways as a potential agent for cancer therapy.
Highlights
In oral cancer, squamous cell carcinoma, is the most common in both genders, followed by verrucous carcinoma, and followed the end of the undiffer-entiated carcinoma, small salivary adenocarcinoma
Effect of HCD and cisplatin on the cell viability of oral cancer cells To test the potency of HCD and cisplatin on cell viability of oral cancer cells, OECM1 and SAS cells were incubated with various concentrations of HCD and cisplatin and incubation time courses (24 and 48 h) to measure the cell viability by a MTT assay
OECM1 and SAS cells were treated with 5, 10, 20, and 50 μM of cisplatin for 24 h, the results indicated that the cell viabilities of both OECM1 and SAS cells were dose-dependent inhibition (P < 0.05) of HCD treatment and IC50 of cisplatin were at concentrations of 23.44 and 38.91 μM in OECM1 and SAS cells, respectively (Figures 1C & 1D)
Summary
Squamous cell carcinoma, is the most common in both genders, followed by verrucous carcinoma, and followed the end of the undiffer-entiated carcinoma, small salivary adenocarcinoma. The anti-cancer chemical drugs including 5-FU, cisplatin, paclitaxel, and Ufur are commonly used to treat oral cancer. 16-Hydroxycleroda-3,13dien-15,16-olide (HCD) and its analogs, extracted from the bark of P. longifolia exhibits strong antiinflammatory activities [9]; enhanced the expression of cyto-protective HO-1 factor and anti-inflammatory enzyme in microglia [10]; the induction of apoptosis in leukemia K562 cells via both a reduction in histone modifying enzymes PRC2-mediated gene silencing and the reactivation of downstream tumor suppressor gene expressions [11] and via PI3K-Akt pathway and Aurora B resulting in gene silencing and cell cycle disturbance [12]. Cisplatin is the most efficient drug used for treating OSCC in clinics It is applied as a positive control in this study to verify the efficacy of testing compounds. Further study was determined HCD that might cause autophagy through the mTOR/PI3K/ Akt/Beclin-1 signaling pathway
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