Quinovic acid purified from medicinal plant Fagonia indica mediates anticancer effects via death receptor 5

Plants are major source for discovery and development of anticancer drugs. Several plant-based anticancer drugs are currently in clinical use. Fagonia indica is a plant of medicinal value in the South Asian countries. Using mass spectrometry and NMR spectroscopy, several compounds were purified from the F. indica extract. We have used one of the purified compounds quinovic acid (QA) and found that QA strongly suppressed the growth and viability of human breast and lung cancer cells. QA did not inhibit growth and viability of non-tumorigenic breast cells. QA mediated its anticancer effects by inducing cell death. QA-induced cell death was associated with biochemical features of apoptosis such as activation of caspases 3 and 8 as well as PARP cleavage. QA also upregulated mRNA and protein levels of death receptor 5 (DR5). Further investigation revealed that QA did not alter DR5 gene promoter activity, but enhanced DR5 mRNA and protein stabilities. DR5 is one of the major components of the extrinsic pathway of apoptosis. Accordingly, Apo2L/TRAIL, the DR5 ligand, potentiated the anticancer effects of QA. Our results indicate that QA mediates its anticancer effects, at least in part, by engaging DR5-depentent pathway to induce apoptosis. Based on our results, we propose that QA in combination with Apo2L/TRAIL can be further investigated as a novel therapeutic approach for breast and lung cancers.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:474

Enthalten in:

Molecular and cellular biochemistry - 474(2020), 1-2 vom: 30. Nov., Seite 159-169

Sprache:

Englisch

Beteiligte Personen:

Khayam, Asma Umer [VerfasserIn]
Patel, Harsh [VerfasserIn]
Faiola, Nicholas A [VerfasserIn]
Figueroa Milla, Andre E [VerfasserIn]
Dilshad, Erum [VerfasserIn]
Mirza, Bushra [VerfasserIn]
Huang, Ying [VerfasserIn]
Sheikh, M Saeed [VerfasserIn]

Links:

Volltext

Themen:

9JP167T0ZN
Antineoplastic Agents, Phytogenic
Apo2L/TRAIL
Breast cancer
DR5
Journal Article
Lung cancer
Natural product
Plant Extracts
Quinovic acid
Receptors, TNF-Related Apoptosis-Inducing Ligand
TNFRSF10B protein, human
Triterpenes

Anmerkungen:

Date Completed 17.05.2021

Date Revised 17.05.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1007/s11010-020-03841-4

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM313100527