Anticancer activity of Bacopa monnieri through apoptosis induction and mitophagy-dependent NLRP3 inflammasome inhibition in oral squamous cell carcinoma

Copyright © 2023 Elsevier GmbH. All rights reserved..

BACKGROUND: Bacopa monnieri (BM) is traditionally used in human diseases for its antioxidant, anti-inflammatory and neuroprotective effects. However, its anticancer potential has been poorly understood.

AIM: The aim of this study was to explore the detailed anticancer mechanism of BM against oral cancer and to identify the bioactive BM fraction for possible cancer therapeutics.

RESULTS: We performed bioactivity-guided fractionation and identified that the aqueous fraction of the ethanolic extract of BM (BM-AF) had a potent anticancer potential in both in vitro and in vivo oral cancer models. BM-AF inhibited cell viability, colony formation, cell migration and induced apoptotic cell death in Cal33 and FaDu cells. BM-AF at low doses promoted mitophagy and BM-AF mediated mitophagy was PARKIN dependent. In addition, BM-AF inhibited arecoline induced reactive oxygen species production in Cal33 cells. Moreover, BM-AF supressed arecoline-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation through mitophagy in Cal33 cells. The in vivo antitumor effect of BM-AF was further validated in C57BL/6J mice through a 4-nitroquinolin-1-oxide and arecoline-induced oral cancer model. The tumor incidence was significantly reduced in the BM-AF treated group. Further, data obtained from western blot and immunohistochemistry analysis showed increased expression of apoptotic markers and decreased expression of inflammasome markers in the tongue tissue obtained from BM-AF treated mice in comparison with the non-treated tumor bearing mice.

CONCLUSION: In conclusion, BM-AF exhibited potent anticancer activity through apoptosis induction and mitophagy-dependent inhibition of NLRP3 inflammasome activation in both in vitro and in vivo oral cancer models. Moreover, we have investigated apoptosis and mitophagy-inducing compounds from this plant extract having anticancer activity against oral cancer cells.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:123

Enthalten in:

Phytomedicine : international journal of phytotherapy and phytopharmacology - 123(2024) vom: 02. Jan., Seite 155157

Sprache:

Englisch

Beteiligte Personen:

Mishra, Soumya Ranjan [VerfasserIn]
Behera, Bishnu Prasad [VerfasserIn]
Singh, Vineet Kumar [VerfasserIn]
Mahapatra, Kewal Kumar [VerfasserIn]
Mundkinajeddu, Deepak [VerfasserIn]
Bhat, Deeksha [VerfasserIn]
Minz, Aruna Mukti [VerfasserIn]
Sethi, Gautam [VerfasserIn]
Efferth, Thomas [VerfasserIn]
Das, Surajit [VerfasserIn]
Bhutia, Sujit Kumar [VerfasserIn]

Links:

Volltext

Themen:

4ALN5933BH
Apoptosis
Arecoline
Bacopa monnieri
Inflammasomes
Journal Article
Mitophagy
NLR Family, Pyrin Domain-Containing 3 Protein
NLRP3 inflammasome
Oral cancer
Reactive Oxygen Species

Anmerkungen:

Date Completed 17.01.2024

Date Revised 17.01.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.phymed.2023.155157

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM364428066