Isolation and characterization of N‐(2‐Hydroxyethyl)hexadecanamide from Colletotrichum gloeosporioides with apoptosis‐inducing potential in breast cancer cells

Abstract

Endophytic fungi are a well-established reservoir of bioactive compounds that are pharmaceutically valuable and therefore, contribute significantly to the biomedical field. The present study aims to identify the bioactive anticancer compound from ethyl acetate extract of fungal endophyte, Colletotrichum gloeosporioides associated with the leaf of the medicinal plant Oroxylum indicum. The fatty acid amide compound N-(2-Hydroxyethyl)hexadecanamide (Palmitoylethanolamide; PEA) was identified using antioxidant activity-guided fractionation assisted with tandem liquid chromatography coupled with quadrupole time of flight mass spectrometry, Fourier transform-infrared spectroscopy, time-of-flight mass spectrometry, and nuclear magnetic resonance.In-Silico molecular docking analysis showed that PEA potentially docked to the active sites of apoptosis-inducing proteins including BAX, BCL-2, P21, and P53. Further validation was done using in vitro study that showed PEA inhibitsthe proliferation, alters nuclear morphology and attenuates the wound closure ability of MDA-MB-231 and MCF-7 cells. PEA induces apoptosis via upregulating cell-cycle arrest (P21), tumor suppression (P53), pro-apoptotic (BAX, CASPASE-8, and FADD) genes, and downregulating anti-apoptotic gene BCL-2. The upregulation of the active form of Caspase-3 was also reported. This is the first-ever report for the isolation of PEA from C. gloeosporioides with anticancer activity against human breast cancer cells and therefore holds great potential for future therapeutics.

Isolation of potassium salt of oxadiazole-2-thione and in vitro anticancer activities of its Cu(ii) and Zn(ii) complexes against MDA-MB-231 human breast carcinoma cells

“…Similar to a previous report, our findings suggest that Kpot·H 2 O and its complexes possess the ability to target reactive oxygen species (ROS) in the proximity of DNA, thereby protecting DNA from harmful radical-induced damage. 58…”

“…Similar to a previous report, our findings suggest that Kpot•H 2 O and its complexes possess the ability to target reactive oxygen species (ROS) in the proximity of DNA, thereby protecting DNA from harmful radical-induced damage. 58 Kpot•H 2 O and its complexes 1 and 2 exhibit cytotoxic activity. The MTT assay is commonly used to assess the viability, proliferation, and cytotoxicity of a chemical compound so that it can be evaluated for its potential as a drug.…”

Exploration of in vitro cytotoxic and in ovo antiangiogenic activity of ethyl acetate extract of Penicillium oxalicum

“…54 According to several studies, the MDA-MB-231 and MCF-7 cells induced apoptosis and displayed the typical morphological changes associated with apoptosis, including cell shrinkage, nuclei blebbing, chromatin condensation, and nuclear fragmentation. [55][56][57][58] Furthermore, the increased expression of genes associated with apoptosis and the stimulation of the pro-apoptotic protein Caspase-3 evidence that the EA extract of P. oxalicum facilitates apoptosis in breast cancer cells. This suggests that the bioactive compound present in the EA extract of P. oxalicum has potential to induce apoptosis, a crucial mechanism for suppressing the growth of breast cancer.…”

Exploring the Protective Effect against 7,12-Dimethylbenz[a]anthracene-Induced Breast Tumors of Palmitoylethanolamide

“…A recent study reported that PEA docked to the active site of apoptosis-inducing proteins Bax, Bcl-2, P21, and P53, and in vitro findings suggest the cytotoxic and apoptosis-inducing ability of PEA against human breast cancer cells . PEA exhibited enhanced pro-apoptotic activity in human breast cancer cells, MDA-MB-231 and MCF-7, through the modulation of gene expression associated with the intrinsic ( BAX , BCL-2 , P21 , and P53 ) and extrinsic ( CASPASE-8 and FADD ) apoptotic pathways . To the best of our knowledge, the preclinical therapeutic potential of PEA in the amelioration of DMBA-induced breast cancer progression is limited.…”

“…PEA, an endocannabinoid-like lipid mediator, is recognized for its anti-inflammatory and neuroprotective properties . A recent study reported that PEA docked to the active site of apoptosis-inducing proteins Bax, Bcl-2, P21, and P53, and in vitro findings suggest the cytotoxic and apoptosis-inducing ability of PEA against human breast cancer cells . PEA exhibited enhanced pro-apoptotic activity in human breast cancer cells, MDA-MB-231 and MCF-7, through the modulation of gene expression associated with the intrinsic ( BAX , BCL-2 , P21 , and P53 ) and extrinsic ( CASPASE-8 and FADD ) apoptotic pathways .…”