Antiproliferative activity and apoptosis-inducing mechanism of Amaryllidaceae alkaloid montanine on A549 and MOLT-4 human cancer cells

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F23%3A10471319" target="_blank" >RIV/00216208:11160/23:10471319 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11150/23:10471319 RIV/00216275:25310/23:39920436

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=QQ23LPWRb7" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=QQ23LPWRb7</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.biopha.2023.115295" target="_blank" >10.1016/j.biopha.2023.115295</a>

Result language

angličtina

Original language name

Antiproliferative activity and apoptosis-inducing mechanism of Amaryllidaceae alkaloid montanine on A549 and MOLT-4 human cancer cells

Original language description

The isoquinoline alkaloids found in Amaryllidaceae are attracting attention due to attributes that can be harnessed for the development of new drugs. The possible molecular mechanisms by which montanine exerts its inhibitory effects against cancer cells have not been documented. In the present study, montanine, manthine and a series of 15 semisynthetic montanine analogues originating from the parent alkaloid montanine were screened at a single test dose of 10 mu M to explore their cytotoxic activities against a panel of eight cancer cell lines and one non-cancer cell line. Among montanine and its analogues, montanine and its derivatives 12 and 14 showed the highest cytostatic activity in the initial single-dose screening. However, the native montanine exhibited the greatest antiproliferative activity against cancer cells, with a lower mean IC50 value of 1.39 mu M, compared to the displayed mean IC50 values of 2.08 mu M for 12 and 3.57 mu M for 14. Montanine exhibited the most potent antiproliferative activity with IC50 values of 1.04 mu M and 1.09 mu M against Jurkat and A549 cell lines, respectively. We also evaluated montanine&apos;s cytotoxicity and cell death mechanisms. Our results revealed that montanine triggered apoptosis of MOLT-4 cells via caspase activation, mitochondrial depolarisation and Annexin V/PI double staining. The Western blot results of MOLT-4 cells showed that the protein levels of phosphorylated Chk1 Ser345 were upregulated with increased montanine concentrations. Our findings provide new insights into the mechanisms underlying the cytostatic, cytotoxic and pro-apoptotic activities of montanine alkaloids in lung adenocarcinoma A549 and leukemic MOLT-4 cancer cell types.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30100 - Basic medicine

Project

<a href="/en/project/EF18_069%2F0010046" target="_blank" >EF18_069/0010046: Pre-application research into innovative medicines and medical technologies</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Biomedicine &amp; Pharmacotherapy

ISSN

0753-3322

e-ISSN

1950-6007

Volume of the periodical

166

Issue of the periodical within the volume

Oct

Country of publishing house

FR - FRANCE

Number of pages

17

Pages from-to

115295

UT code for WoS article

001062266400001

EID of the result in the Scopus database

2-s2.0-85167975554