6,8‐Diprenylorobol induces apoptosis in human colon cancer cells via activation of intracellular reactive oxygen species and p53

Abstract

6,8‐Diprenylorobol is a natural compound mainly found in Glycyrrhiza uralensis fisch and Maclura tricuspidata, which has been used traditionally as food and medicine in Asia. So far, the antiproliferative effect of 6,8‐diprenylorobol has not been studied yet in colon cancer. In this study, we aimed to evaluate the antiproliferative effects of 6,8‐diprenylorobol in LoVo and HCT15, two kinds of human colon cancer cells. 6,8‐Diprenylorobol inhibited the proliferation of LoVo and HCT15 cells in a dose‐ and time‐dependent manner. A 40 μM of 6,8‐diprenylorobol for 72 h reduced both of cell viability under 50%. After treatment of 6,8‐diprenylorobol (40 and 60 μM) for 72 h, late apoptotic cell portion in LoVo and HCT15 cells were 24, 70% and 13, 90%, respectively, which was confirmed by checking DNA fragmentation in both cells. Mechanistically, 6,8‐diprenylorobol activated p53 and its phosphorylated form (Ser15, Ser20, and Ser46) expression but suppressed Akt and mitogen‐activated protein kinases (MAPKs) phosphorylation in LoVo and HCT15 cells. Interestingly, 6,8‐diprenylorobol induced the generation of intracellular reactive oxygen species (ROS), which was attenuated with N‐acetyl cysteine (NAC) treatment. Compared to the control, 60 μM of 6,8‐diprenylorobol caused to increase ROS level to 210% in LoVo and HCT15, which was reduced into 161% and 124%, respectively with NAC. Furthermore, cell viability and apoptotic cell portion by 6,8‐diprenylorobol was recovered by incubation with NAC. Taken together, these results indicate that 6,8‐diprenylorobol has the potential antiproliferative effect against LoVo and HCT15 colon cancer cells through activation of p53 and generation of ROS.

Inhibitory Effects of 6,8-Diprenylorobol on Endometriosis Progression in Humans by Disrupting Calcium Homeostasis and Mitochondrial Function

“…Even these limited studies of the bioactive effects of 6,8-diprenylorobol have mainly been conducted for cancers. In a previous study, 6,8-diprenylorobol exhibited antiproliferative and apoptotic effects, and increased the production of ROS in colon cancer [ 17 ]. In addition, 6,8-diprenylorobol suppressed cell viability and induced apoptosis in human liver cancer cells (HCC) via regulation of FOXO3 and CYP2J2 [ 16 ].…”

“…For example, 6,8-diprenylorobol indicated an anticancer effect that induced apoptosis in hepatocellular carcinoma cell lines by inhibiting cytochrome P450 family 2 subfamily J member 2 (CYP2J2) and activating forkhead box O3 (FOXO3) [ 16 ]. In addition, 6,8-diprenylorobol induced apoptosis in colon cancer by activating the P53 apoptotic cell signal pathway [ 17 ]. However, the antiproliferation effects of 6,8-diprenylorobol on human endometriosis have not yet been identified.…”

The silkworm (Bombyx mori) gut microbiota is involved in metabolic detoxification by glucosylation of plant toxins

“…HUVECs were obtained from the Shanghai Institute for Biological Sciences (SIBS), China Academy of Sciences (China). According to a previously reported method 66 , the culture conditions of HUVECs were RPMI-1640 (HyClone) medium consisting of 10% FBS (Sijiqing Company Ltd.), 100 units/mL penicillin G and 100 μg/mL streptomycin in an environment with 5% CO 2 at 37 °C. Cells from the HUVEC line were first seeded into 96-well plates at 3−5 × 103 cells/well and allowed to adhere overnight.…”

“…Cell apoptosis and cell cycle arrest were analysed by flow cytometry according to the literature 66 – 68 with minor modifications as followed. Briefly, after overnight incubation, the cells were exposed to 5% serum medium with concentrations of 0, 2.5, 5, and 10 μM DPL ( 24 ) for 24 h and then harvested and washed with PBS.…”

Metal-Organic Framework-Based Nanotherapeutics With Tumor Hypoxia-Relieving Ability for Synergistic Sonodynamic/Chemo-therapy

“…Due to the excellent thermal and hydrothermal stability, ZIFs have been applied in gas storage, drug carriers, and other biological applications (Banerjee et al, 2008;Wang et al, 2008). Additionally, ZIF-8 has gained attention for its low toxicity under certain conditions (Adhikari et al, 2015) and can be synthesized from zinc ion and 2-methylimidazole (Guo et al, 2020;Choi et al, 2021). In addition, as a stable solvent in a neutral aqueous microenvironment, ZIF-8 can only be decomposed in acidic solutions, indicating its application as a pH-sensitive drug delivery carrier.…”