Caffeine–hydrazones as anticancer agents with pronounced selectivity toward T-lymphoblastic leukaemia cells

Kaplánek, Robert; Jakubek, Milan; Rak, Jakub; Kejík, Zdeněk; Havlík, Martin; Dolenský, Bohumil; Frydrych, Ivo; Hajdúch, Marián; Kolář, Milan; Bogdanová, Kateřina; Králová, Jarmila; Džubák, Petr; Král, Vladimír

doi:10.1016/j.bioorg.2015.03.003

Cited by 47 publications

(21 citation statements)

References 28 publications

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“…Importantly, CYP1 family enzymes were not expressed in MCF-10a cells 9 . Thus, eupatorin at 5 μg/mL did not affect the viability of human normal breast MCF-10a cells and was found highly selective towards cancer cells indicated by SI>3 21,22 . Interestingly, although the IC 50 value of eupatorin was far higher than the common anticancer drug doxorubicin on both cancer cell lines, the MCF-10a vs MCF7 and MCF-10a vs MDA-MB-231 SI values of eupatorin were 6.5 and 8.8 times higher than doxorubicin, respectively.…”

Section: Discussionmentioning

confidence: 86%

Cytotoxicity of eupatorin in MCF-7 and MDA-MB-231 human breast cancer cells via cell cycle arrest, anti-angiogenesis and induction of apoptosis

Razak

Abu

et al. 2019

Sci Rep

162

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Eupatorin has been reported with in vitro cytotoxic effect on several human cancer cells. However, reports on the mode of action and detail mechanism of eupatorin in vitro in breast cancer disease are limited. Hence, eupatorin’s effect on the human breast carcinoma cell line MCF-7 and MDA-MB-231 was investigated. MTT assay showed that eupatorin had cytotoxic effects on MCF-7 and MDA-MB-231 cells but was non-toxic to the normal cells of MCF-10a in a time-dose dependent manner. At 24 h, the eupatorin showed mild cytotoxicity on both MCF-7 and MDA-MB-231 cells with IC50 values higher than 20 μg/mL. After 48 h, eupatorin at 5 μg/mL inhibited the proliferation of MCF-7 and MDA-MB-231 cells by 50% while the IC50 of MCF-10a was significantly (p < 0.05) high with 30 μg/mL. The concentration of eupatorin at 5 μg/mL induced apoptosis mainly through intrinsic pathway by facilitating higher fold of caspase 9 compared to caspase 8 at 48 h. The cell cycle profile also showed that eupatorin (5 μg/mL) exerted anti-proliferation activity with the cell cycle arrest of MCF-7 and MDA-MB-231 cells at sub Gθ/G1 in a time-dependent manner. In addition, wound healing assay showed an incomplete wound closure of scratched MDA-MB-231 cells, and more than 60% of the MDA-MB-231 cells were prevented to migrate and invade the membrane in the Boyden chamber after 24 h. Eupatorin also inhibited angiogenic sprouting of new blood vessels in ex vivo mouse aorta ring assay. In gene expression assay, eupatorin up-regulated pro-apoptotic genes such as Bak1, HIF1A, Bax, Bad, cytochrome c and SMAC/Diablo and blocked the Phospho-Akt pathway. In conclusion, eupatorin is a potent candidate to induce apoptosis and concurrently inhibit the invasion, migration and angiogenesis of MDA-MB-231 and MCF-7 cells through inhibition of Phospho-Akt pathway and cell cycle blockade.

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Section: Discussionmentioning

confidence: 86%

Cytotoxicity of eupatorin in MCF-7 and MDA-MB-231 human breast cancer cells via cell cycle arrest, anti-angiogenesis and induction of apoptosis

Razak

Abu

et al. 2019

Sci Rep

162

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“…N -(1′-Naphthyl)-3,4,5-trimethoxybenzohydrazide has been reported as a potential anti-leukemia agent acting as a microtubule destabilizer [11]. 2- N -Heteroaryl caffeine hydrazones demonstrated high activity toward T-lymphoblastic leukemia cells and inhibited both RNA and DNA synthesis and mitosis [12]. 4-(2-Fluorophenoxy)quinolineacylhydrazones showed excellent antiproliferative activity and c-Met kinase inhibitory activity [13].…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Evaluation of Antiproliferative Activity of New Benzimidazolehydrazones

et al. 2016

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Abstract:The synthesis and antiproliferative activity of new benzimidazole derivatives bearing an hydrazone mojety at the 2-position is described. The new N 1 -(4-arylidene)-1H-benzo[d]imidazole-2-carbohydrazides were evaluated for their cytostatic activity toward the murine leukemia (L1210), human T-cell leukemia (CEM), human cervix carcinoma (HeLa) and human pancreas carcinoma cells (Mia Paca-2). A preliminary structure-activity relationship could be defined. Some of the compounds possess encouraging and consistent antiproliferative activity, having IC 50 values in the low micromolar range.

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“…IC 50 values of caffeine against p53 wild type HC116 and CEM/ ADR5000 were even higher than the highest concentration tested (500 µM). Kaplanek et al [23] evaluated caffeine up to 25 µM for 72 h and found IC 50 to be higher than 25 µM against seven cancer cell lines including the four cancer cell types what we investigated currently. Nevertheless, these authors demonstrated a significant suppressing effect on proliferation by increasing the doses of caffeine (the maximum inhibition being achieved at 5000 µM).…”

Section: Resultsmentioning

confidence: 93%

In vitro anti-proliferative activity of selected nutraceutical compounds in human cancer cell lines

2021

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Objective We investigated the anti-proliferative or cytotoxic activities of five nutraceutical compounds: allyl isothiocyanate, β-carotene, caffeine, capsaicin, and lupanine that we consume respectively, for example, from mustard seeds, carrot, coffee, pepper, and lupin seeds against cancer cell lines (human colon: HCT 116 p53 wild type, HCT 116 p53−/− and lymphoblastic: CEM/CCRF, CEM/ADR5000). Result Out of the five compounds tested in vitro, capsaicin and β-carotene were more cytotoxic than the other three compounds against the four cancer cell lines. The most potent nutraceutical compound was capsaicin and it exerted its highest cytotoxicity against HCT 116 p53−/− with IC50 value of 19.67 ± 0.06 µM. It is worth considering capsaicin for further development of anticancer drug against both colon and leukemia cancer types.

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Caffeine–hydrazones as anticancer agents with pronounced selectivity toward T-lymphoblastic leukaemia cells

Cited by 47 publications

References 28 publications

Cytotoxicity of eupatorin in MCF-7 and MDA-MB-231 human breast cancer cells via cell cycle arrest, anti-angiogenesis and induction of apoptosis

Cytotoxicity of eupatorin in MCF-7 and MDA-MB-231 human breast cancer cells via cell cycle arrest, anti-angiogenesis and induction of apoptosis

Design, Synthesis and Evaluation of Antiproliferative Activity of New Benzimidazolehydrazones

In vitro anti-proliferative activity of selected nutraceutical compounds in human cancer cell lines

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