SL4, a chalcone‐based compound, induces apoptosis in human cancer cells by activation of the ROS/MAPK signalling pathway

Abstract

These data demonstrate that SL4 induced apoptosis in human cancer cells through activation of the ROS/MAPK signalling pathway, suggesting that it may be a novel lead compound, as a cancer drug candidate, with polypharmacological characteristics.

Quantitative Structure–Cytotoxicity Relationship of Chalcones

“…Chalcones are promising lead antitumor/chemopreventive drugs due to three different activities: antioxidant, cytotoxic, and apoptosis induction (2). Several studies with murine xenograft models have shown that administration of chalcones significantly reduced the tumor volume by inducing apoptosis (3)(4)(5)(6)(7)(8)(9)(10). The tumor specificity of chalcones has been reported in comparing sensitivity of hepatocarcinoma HepG2 cells to normal liver AML12 cells (11); osterosarcoma to bone marrow and smallintestinal epithelial cells (12); murine acute lymphoblastic leukemia cells L-1210 to normal human lymphocytes (13); and human prostate cancer cells PC3 and DU145 to normal human prostate epithelial cells (14).…”

Anti-tumor activity of SL4 against breast cancer cells: induction of G2/M arrest through modulation of the MAPK-dependent p21 signaling pathway

“…The IC 50 values were 1.1 ± 0.2 μM, 0.5 ± 0.1 μM, 1.3 ± 0.1 μM and 0.3 ± 0.1 μM for MCF-7, MDA-MB-231, MDA-MB-436 and Bcap37 cell lines, respectively. These values are lower than our previously reported IC 50 (16.9 ± 2.4 μM) for SL4 on normal MCF-10A breast cells16. Given their sensitivity to SL4 and their genotype-phenotype characteristics, we selected MCF-7 (ER+, PR+, HER2-, and p53 wild type) and MDA-MB-231 (ER-, PR-, HER2-, and p53 mutation) for subsequent experiments.…”

“…SL4 was administered at a dose of 2.5 or 5.0 mg/kg, in accordance with our previous report16. As shown in Fig.…”

“…Our previous study revealed that a novel chalcone-based compound SL4 (also named 5d; Fig. 1A) showed obvious anti-invasive and anti-angiogenic potential by suppressing HIF-1 activity and displayed a remarkable ability to induce cell apoptosis by enhancing ROS accumulation1516. Notably, studies by other groups demonstrated that chalcone-based compounds can also arrest the cell cycle in several cancer cells171819.…”

Chrysotoxene induces apoptosis of human hepatoblastoma HepG2 cells in�vitro and in�vivo via activation of the mitochondria-mediated apoptotic signaling pathway

“…C-caspase-9 can induce the cleavage of procaspase-3 (c-caspase-3), which induces apoptosis of cells (21). The cleavage of procaspase-3 caused by c-caspase-9 can be inhibited by Survivin, whose function can be attenuated by Smac in the cytoplasm (22,23). The results of western blot analysis in the present study indicated that chrysotoxene induced the apoptosis of HepG2 cells by promoting the release of Smac and Cytochrome c from the mitochondria to the cytoplasm, downregulating Survivin and Bcl-2 protein levels, and upregulating Bax, Apaf-1, c-caspase-9 and c-caspase-3 protein levels (Figs.…”