N,N-Dimethyl-anthranilic Acid from Calvatia nipponica Mushroom Fruiting Bodies Induces Apoptotic Effects on MDA-MB-231 Human Breast Cancer Cells

Breast cancer ranks among the most prevalent malignancies affecting women worldwide, and apoptosis-targeting drugs are attractive candidates for the treatment of cancer. In the current study, we investigated the in vitro cytotoxicity of the mushroom Calvatia nipponica in human breast cancer cells (MDA-MB-231), identified potential antitumor compounds through bioactivity-guided isolation, and elucidated the antitumor, pro-apoptotic molecular mechanisms of the identified bioactive compounds. C. nipponica is edible when young, and it has been used as a food source as well as a traditional medicine in wound dressings. However, only a limited number of studies have reported its chemical composition and biological activities. In the screening test, the methanol extract of C. nipponica fruiting bodies exhibited cytotoxicity against MDA-MB-231 cells. Bioactivity-guided fractionation of the methanol (MeOH) extract and chemical investigation of the active fractions resulted in the isolation of fourteen compounds (1-14), including six alkaloids (1-3, 5, 7, and 8), two phenolic compounds (4 and 6), one fatty acid (9), and five steroids (10-14). The structures of the isolated compounds were determined using NMR spectroscopic methods, liquid chromatography-mass spectrometry, and comparison of data with previously reported values. The isolated compounds (1-14) were tested for cytotoxicity against MDA-MB-231 cells, where compound 1, i.e., N,N-dimethyl-anthranilic acid, exhibited the most significant cytotoxicity against MDA-MB-231 cells, with an IC50 value of 90.28 ± 4.23 μM and apoptotic cell death of 56.01% ± 2.64% at 100 μM. Treatment with compound 1 resulted in an upregulation of protein levels, including cleaved caspase-8, cleaved poly (ADP-ribose) polymerase, Bcl-2-associated X protein (Bax), cleaved caspase-3, cleaved caspase-9, Bad, and Cytochrome c, but decreased the levels of B-cell lymphoma 2 (Bcl-2). Overall, these results indicate that N,N-dimethyl-anthranilic acid (1) may have anti-breast cancer activity and is probably involved in the induction of apoptosis mediated by extrinsic and intrinsic signaling pathways.

Media Type:

Electronic Article

Year of Publication:

2023

Publication:

2023

Contained In:

To Main Record - volume:15

Contained In:

Nutrients - 15(2023), 14 vom: 10. Juli

Language:

English

Contributors:

Lee, Dahae [Author]
Lee, Seulah [Author]
Jang, Yoon Seo [Author]
Ryoo, Rhim [Author]
Kim, Jung Kyu [Author]
Kang, Ki Sung [Author]
Kim, Ki Hyun [Author]

Links:

Volltext

Keywords:

0YS975XI6W
Anthranilic acid
Apoptosis
Breast cancer cells
Calvatia nipponica
EC 2.4.2.30
Journal Article
MDA-MB-231
Methanol
N,N-dimethyl-anthranilic acid
Poly(ADP-ribose) Polymerases
Y4S76JWI15

Notes:

Date Completed 31.07.2023

Date Revised 01.08.2023

published: Electronic

Citation Status MEDLINE

doi:

10.3390/nu15143091

funding:

Supporting institution / Project title:

PPN (Catalogue-ID):

NLM360133819