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

Kód výsledku v 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>

Nalezeny alternativní kódy

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

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30100 - Basic medicine

Projekt

<a href="/cs/project/EF18_069%2F0010046" target="_blank" >EF18_069/0010046: Předaplikační výzkum inovativních léčiv a medicínských technologií</a><br>

Návaznosti

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

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Biomedicine &amp; Pharmacotherapy

ISSN

0753-3322

e-ISSN

1950-6007

Svazek periodika

166

Číslo periodika v rámci svazku

Oct

Stát vydavatele periodika

FR - Francouzská republika

Počet stran výsledku

17

Strana od-do

115295

Kód UT WoS článku

001062266400001

EID výsledku v databázi Scopus

2-s2.0-85167975554