Dutch
Albanian
Arabic
Armenian
Azerbaijani
Belarusian
Bengali
Bosnian
Catalan
Czech
Danish
Deutsch
Dutch
English
Estonian
Finnish
Français
Greek
Haitian Creole
Hebrew
Hindi
Hungarian
Icelandic
Indonesian
Irish
Italian
Japanese
Korean
Latvian
Lithuanian
Macedonian
Mongolian
Norwegian
Persian
Polish
Portuguese
Romanian
Russian
Serbian
Slovak
Slovenian
Spanish
Swahili
Swedish
Turkish
Ukrainian
Vietnamese
Български
中文(简体)
中文(繁體)
Anti-Cancer Agents in Medicinal Chemistry 2020-Sep

Chloroform Fraction of Methanolic Extract of Seeds of Annona muricata Induce S Phase Arrest and ROS Dependent Caspase Activated Mitochondria Mediated Apoptosis in Triple Negative Breast Cancer

Alleen geregistreerde gebruikers kunnen artikelen vertalen
Log in Schrijf in
De link wordt op het klembord opgeslagen
Ajith George
Bibu Kariyil
Usha Ayyappan
Anu Gopalakrishnan

Sleutelwoorden

Abstract

Background: Triple negative breast cancers (TNBCs) are having high morbidity and shorter survival rate in the population. These types of cancers are having high aggressiveness, lymphatic invasion and absence of receptors. The treatment options for these types of cancers are also scarce. Several studies have been conducted to investigate the effectiveness of seeds of Annona muricata for its anti cancer activities in various cancer cell lines such as lung A549, breast MCF7, colon HT-29, oral KB and human hepatoma cell lines. But works related to its anticancer effect and mechanism of action in TNBCs has not been elucidated.

Objective: The present study was undertaken to evaluate the in vitro, in vivo and in silico anticancer potential of chloroform fraction of methanolic extract of seeds of Annona muricata (CMAM) against TNBC along with elucidation of its mechanistic pathway.

Methods: In vitro cytotoxicity- and antiproliferative- studies in three triple negative breast cancer cell lines were conducted using MTT and SRB assays respectively. The mechanism through which CMAM exerts its pharmacological effect was elucidated in vitro employing cell morphological assessment studies using acridine orange/ ethidium bromide (AO/EB), intra cellular reactive oxygen species assay, DNA fragmentation assay, agarose gel electrophoresis, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cell cycle analysis, annexin binding assay and caspase activated mitochondria mediated apoptotic assays using western blot. In vivo evaluation in 4T1 induced murine mammary tumour model was also conducted. Phytoconstituents in CMAM was analysed using liquid chromatography mass spectroscopy. In silico binding studies with various annonaceous acetogenins against BCL-2 and cyclin E were performed.

Results: Cytotoxicity studies in MDA-MD-231, 4TI and BT-549 revealed the IC50 value of CMAM to be 2.5±0.14, 4.8±0.3 and 4.5±0.16 µg/mL respectively. Anti proliferative studies in 4T1, MDA-MB-231 and BT-549 revealed the GI50 values to be 0.128+0.03, 18.03+0.20, 0.95+0.04 µg/mL respectively. CMAM exhibited its cytotoxicity through the lysis of cell membrane, ROS dependent caspase activated mitochondria mediated apoptosis, and arresting the S phase of the cell cycle. In vivo evaluation also supported the tumoricidal property of CMAM as evidenced by reduction in tumour volume and serum biomarkers. Histopathologically there was a marked reduction in cellularity, nuclear chromatin condensation and a few normal cells in group treated with CMAM at a dose of 31mg/Kg. Phytoconstituent evaluation has revealed the presence of annonaceous acetogenins in CMAM. Among the various annonaceous acetogenins, muricatacin alone showed lipophilicity and binding affinity towards BCL-2 and cyclin E1.

Conclusion: The current study shows the effectiveness of CMAM against TNBC both in vitro and in vivo. This anticancerous effect of CMAM could be by virtue of its ROS dependent caspase activated mitochondria mediated apoptosis and the S-phase arrest of the cell cycle in the TNBCs. Our results indicate that the presence of annonaceous acetogenins, especially muricatacin, could be contributing to this anticanceros effect of CMAM. Thus muricatacin could be a potential candidate for the targeted therapy of TNBCs.

Keywords: Annonaceous acetogenins; ROS dependent; Sphase arrest; apoptosis; caspase mediated; in silico studies; intrinsic pathway; triple negative breast cancer cells.

Word lid van onze
facebookpagina

De meest complete database met geneeskrachtige kruiden, ondersteund door de wetenschap

  • Werkt in 55 talen
  • Kruidengeneesmiddelen gesteund door de wetenschap
  • Kruidenherkenning door beeld
  • Interactieve GPS-kaart - tag kruiden op locatie (binnenkort beschikbaar)
  • Lees wetenschappelijke publicaties met betrekking tot uw zoekopdracht
  • Zoek medicinale kruiden op hun effecten
  • Organiseer uw interesses en blijf op de hoogte van nieuwsonderzoek, klinische onderzoeken en patenten

Typ een symptoom of een ziekte en lees over kruiden die kunnen helpen, typ een kruid en zie ziekten en symptomen waartegen het wordt gebruikt.
* Alle informatie is gebaseerd op gepubliceerd wetenschappelijk onderzoek

Google Play badgeApp Store badge