1. Academic Validation
  2. Apoptosis-mediated anticancer activity in prostate cancer cells of a chestnut honey (Castanea sativa L.) quinoline-pyrrolidine gamma-lactam alkaloid

Apoptosis-mediated anticancer activity in prostate cancer cells of a chestnut honey (Castanea sativa L.) quinoline-pyrrolidine gamma-lactam alkaloid

  • Amino Acids. 2021 Jun;53(6):869-880. doi: 10.1007/s00726-021-02987-9.
Giangiacomo Beretta 1 Roberta Manuela Moretti 2 Rita Nasti 3 Raffaella Cincinelli 4 Sabrina Dallavalle 5 Marina Montagnani Marelli 2
Affiliations

Affiliations

  • 1 Department of Environmental Science and Policy, University of Milan, 20133, Milan, Italy. giangiacomo.beretta@unimi.it.
  • 2 Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133, Milan, Italy.
  • 3 Department of Environmental Science and Policy, University of Milan, 20133, Milan, Italy.
  • 4 Department of Pharmaceutical Sciences, University of Milan, 20133, Milan, Italy.
  • 5 Department of Food, Environmental and Nutritional Sciences, University of Milan, 20133, Milan, Italy.
Abstract

Prostate Cancer (PCa) is the most common malignancy in men and represents the second leading cause of Cancer deaths in Western countries. PCa is initially androgen-dependent, however, this tumor inevitably progresses as castration-resistant prostate Cancer (CRPC), which represents the most aggressive phase of the pathology. In this work, in two CRPC cell lines (DU145 and PC3), we studied the in vitro inhibitory properties of the tryptophan-derived Endogenous Metabolite kynurenic acid (KYNA) and of the lactam form of 3-2'-pyrrilonidinyl-kynurenic acid (3-PKA-L), Alkaloids usually present in combination in chestnut honey. Cytotoxicity was evaluated by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell colony formation assay, and Western blot analysis of the major mediator proteins involved in apoptotic processes. In all experiments, KYNA was scarcely or not active while 3-PKA-L showed Anticancer activity in the high concentration range (0.01 mM - 1 mM) from 24 to 72 h. The results obtained showed that cell death was induced by extrinsic apoptotic pathway, by cell morphological changes and reduction of cell colonies number. These novel results represent the first promising step to the accurate description of 3-PKA-L cytotoxic effect, not observed with KYNA, paving the way to the search of new Anticancer agents, as well as to the better understanding of the physiopathological role of this interesting natural product.

Keywords

Apoptosis; Kynurenic acid; Prostate cancer; Quinoline alkaloids; Tryptophan metabolism.

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  • HY-101297
    ≥98.0%, Caspase-8抑制剂