CLEFMA Induces the Apoptosis of Oral Squamous Carcinoma Cells through the Regulation of the P38/HO-1 Signalling Pathway

Abstract

The purpose of this research was to evaluate the impact and the underlying molecular mechanism of CLEFMA-induced cell death in human OSCC. The anti-tumour properties of CLEFMA in oral cancer were explored using colony formation, flow cytometry, human apoptosis array, Western blot, and immunohistochemistry assays. The in vivo anti-tumour effect of CLEFMA administered by oral gavage was evaluated using SCC-9-derived xenograft-bearing nude mouse models. CLEFMA significantly suppressed colony formation and elicited cellular apoptosis in oral cancer cells. CLEFMA treatment remarkably increased phosphorylated p38 and HO-1 along with cleavage of poly ADP-ribose polymerase and activation of caspase-8, -9, and -3 in HSC-3 and SCC-9 cells. Administration of HO-1 small interfering RNA significantly protected the cells from CLEFMA-induced caspase-3, -8, and -9 activation. Attenuation of p38 activity by the pharmacologic inhibitor SB203580 dramatically reduced CLEFMA-induced caspase-3, -8, and -9 activation and HO-1 expression in OSCC. The subcutaneous murine xenograft models showed that CLEFMA in vivo suppressed tumour growth in implanted SCC-9 cells. All of these findings indicated that CLEFMA induced apoptosis through the p38-dependent rise in HO-1 signal transduction cascades in OSCC.

Hispolon induces apoptosis in oral squamous cell carcinoma cells through JNK/HO‐1 pathway activation

“…49 Nevertheless, up-regulation of HO-1 is also found in drug-mediated tumour apoptosis, especially in head and neck squamous cell carcinoma. Our previous studies have indicated that curcumin analogues increased HO-1 expression in OSCC apoptosis through MAPK pathways, 28,29 which agrees with our present study that HO-1 is overexpressed in hispolon-induced apoptosis.…”

“…Human siRNAs for non‐specific control and HO‐1 were obtained from Ambion Inc. The transfection of siRNA was using Lipofectamine RNAi MAX reagent (Invitrogen) by following a previously described process 28,29 . At 48 h after transfection, cells were used for HO‐1 detection by Western blotting assay.…”

CLEFMA induces intrinsic and extrinsic apoptotic pathways through ERK1/2 and p38 signalling in uterine cervical cancer cells

“…21 CLEFMA possesses superior bioavailability and solubility to those of curcumin; it also exerts antiproliferative effects on cancer cells 8,22 and is a potential active anticancer compound. 23,24 Moreover, CLEFMA was demonstrated to have the potential to induce cell death in lung adenocarcinoma cells. 9 To date, no study has investigated the effect of CLEFMA on cervical cancer cells.…”