AI Article Synopsis
- Recalcitrant cancers pose challenges for chemotherapy, prompting research into new drugs for multi-drug resistant (MDR) cancer cell lines.* -
- This study tested a ferrulic acid derivative, DHCF2, on 18 different cancer cell lines to assess its cancer-fighting properties and mechanisms of cell death.* -
- Results showed DHCF2 had strong cytotoxic effects, with IC values lower than those of the reference drug doxorubicin, indicating its potential as an effective treatment for resistant cancers through mechanisms like autophagy and apoptosis.*
Article Abstract
Background: Recalcitrant cancers appear as a major obstacle to chemotherapy, prompting scientists to intensify the search for novel drugs to tackle the cell lines expressing multi-drug resistant (MDR) phenotypes.
Purpose: The purpose of this study was to evaluate the antiproliferative potential of a ferrulic acid derivative, 8,8-bis-(dihydroconiferyl)-diferulate (DHCF2) on a panel of 18 cancer cell lines, including various sensitive and drug-resistant phenotypes, belonging to human and animals. The mode of induction of cell death by this compound was further studied.
Methods: The antiproliferative activity, autophagy, ferroptotic and necroptotic cell death were evaluated by the resazurin reduction assay (RRA). CCRF-CEM leukemia cells were used for all mechanistic studies. A caspase-Glo assay was applied to evaluate the activity of caspases. Cell cycle analysis (PI staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP) (JC-1) and reactive oxygen species (ROS) (HDCFH-DA) were assessed by flow cytometry.
Results: DHCF2 demonstrated impressive cytotoxic effects towards the 18 cancer cell lines tested, with IC values all below 6.5 µM. The obtained IC values were in the range of 1.17 µM (towards CCRF-CEM leukemia cells) to 6.34 µM (towards drug-resistant HCT116 p53 human colon adenocarcinoma cells) for DHCF2 and from 0.02 µM (against CCRF-CEM cells) to 122.96 µM (against multidrug-resistant CEM/ADR5000 leukemia cells) for the reference drug, doxorubicin. DHCF2 had IC values lower than those of doxorubicin, against CEM/ADR5000 cells and on some melanoma cell lines, such as MaMel-80a cells, Mel-2a cells, MV3 cells and SKMel-505 cells. DHCF2 induced autophagy as well as apoptosis in CCRF-CEM cells though caspases activation, MMP alteration and increase of ROS production.
Conclusion: The studied diferulic acid, DHCF2, is a promising antiproliferative compound. It deserves further indepth investigations with the ultimate aim to develop a novel drug to fight cancer drug resistance.
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| http://dx.doi.org/10.1016/j.phymed.2020.153215 | DOI Listing |
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