Cytotoxicity of trans-chalcone and licochalcone A against breast cancer cells is due to apoptosis induction and cell cycle arrest

Bortolotto, Luis Felipe Buso; Barbosa, Flávia Regina; Silva, Gabriel; Bitencourt, Tamires Aparecida; Beleboni, Renê Oliveira; Baek, Seung Joon; Marins, Mozart; Fachin, Ana Lúcia

doi:10.1016/j.biopha.2016.11.047

Cited by 84 publications

(73 citation statements)

References 28 publications

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“…The potency of LicA in different tumor types is highly different. As reported, breast cancer cells demonstrated high sensitivity to LicA with an IC 50 of 20 µM (16), and the iC 50 of licA in cervical cancer and head and neck cancer was 40 and 100 µM, respectively (18,19). in our study, the IC 50 of LicA in gastric cancer was ~60 µM, which was in accordance with the results reported by Hao et al (24).…”

Section: Discussionsupporting

confidence: 92%

“…LicA was reported to possess different biological activities, including anti-oxidative (13), anti-inflammatory (14), antiviral and antimicrobial activities (15). Recently, increasing evidence has demonstrated that LicA exhibits profound antitumor activities in various types of cancers, such as breast (16), non-small cell lung (17) and cervical cancer. Induction of cell apoptosis, cell cycle arrest and autophagy (16,18,19), inhibition of migration and metastasis (20), and blockade of angiogenesis in tumor tissues (21) have been identified to be the underlying mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Licochalcone A suppresses hexokinase 2-mediated tumor glycolysis in gastric cancer via downregulation of the Akt signaling pathway

Zhang

Wang

et al. 2017

Oncol Rep

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Licochalcone A (LicA) is a chalcone extracted from liquorice which has been used as a traditional Chinese medicine for many generations. Increased glucose consumption and glycolytic activity are important hallmarks of cancer cells, and hexokinase 2 (HK2) upregulation is a major contributor to the elevation of glycolysis. Recently, the antitumor activities of LicA have been reported in various cancers; however, its effect on tumor glycolysis in gastric cancer and the underlying mechanisms are completely unknown. In vitro, cell proliferation and clonogenic survival were substantially inhibited after LicA treatment. LicA reduced HK2 expression, and both glucose consumption and lactate production in gastric cancer cells were significantly suppressed. Mechanistic investigations revealed that multiple signaling pathways including Akt, ERK and NF‑κB were suppressed by LicA. Further studies demonstrated that the inhibition of glycolysis by LicA was mainly attributed to the blockade of the Akt signaling pathway, and the suppression of glycolysis was substantially attenuated when Akt was exogenously overexpressed. In addition to the role in the inhibition of glycolysis, reduction in HK2 was confirmed to be involved in the induction of cell apoptosis. The apoptosis induced by LicA was substantially impaired after HK2 overexpression in gastric cancer cells. The in vivo experiment showed that MKN45 xenograft growth was markedly delayed after LicA treatment and HK2 expression in LicA‑treated tissues was markedly decreased. All of these data demonstrated that blockade of the Akt/HK2 pathway was the underlying mechanism required for LicA to exert its biological activities in glycolysis inhibition and apoptosis induction.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Licochalcone A suppresses hexokinase 2-mediated tumor glycolysis in gastric cancer via downregulation of the Akt signaling pathway

Zhang

Wang

et al. 2017

Oncol Rep

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“…Chalcones are known to induce apoptosis in several cancer cells, being able to up regulate more than 15 pro-apoptotic markers expression, such as Bad, Bax, Bid, Bim, CD40, Fas, IGFBP-5, IGFBP-6, p21, and sTNF-R116. Hsu and Bortolloto and their respective collaborators have demonstrated pro-apoptotic activity of unsubstituted chalcone against MCF-7 breast cancer cells 38,39 . These authors have described intrinsic apoptotic pathway induced by unsubstituted chalcone, with inhibition of Bcl-2 and induction of Bax apoptotic markers.…”

Section: Pro-apoptotic Activity Of Selected Chalcones 11 and 17mentioning

confidence: 99%

Antiproliferative activity and p53 upregulation effects of chalcones on human breast cancer cells

Santos

Anselmo

Oliveira

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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Chalcones are valuable structures for drug discovery due to their broad bioactivity spectrum. In this study, we evaluated 20 synthetic chalcones against estrogen-receptor-positive breast cancer cells (MCF-7 line) and triple-negative breast cancer (TNBC) cells (MDA-MB-231 line). Antiproliferative screening by MTT assay resulted in two most active compounds: 2-fluoro-4'-aminochalcone (11) and 3-pyridyl-4'-aminochalcone (17). Their IC 50 values ranged from 13.2 to 34.7 mM against both cell lines. Selected chalcones are weak basic compounds and maintained their antiproliferative activity under acidosis conditions (pH 6.7), indicating their resistance to ion-trapping effect. The mode of breast cancer cells death was investigated and chalcones 11 and 17 were able to induce apoptosis rather than necrosis in both lines. Antiproliferative target investigations with MCF-7 cells suggested 11 and 17 upregulated p53 protein expression and did not affect Sp1 protein expression. Future studies on chalcones 11 and 17 can define their in vivo therapeutic potential.

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“…Aside from this antioxidant ability, the anticancer potential of flavonoids also depends on their ability to interact with Phase I and II enzymes involved in procarcinogen biotransformation, as well as their ability to inhibit the enzymes involved in DNA replication. Additionally, flavonoids modulate cyclin activity, thus arresting cell cycle (phases G1/S or G2/M), inhibiting cancer cell proliferation and inducing apoptosis (48).…”

Section: Introductionmentioning

confidence: 99%

Flavonoids, bioactive components of propolis, exhibit cytotoxic activity and induce cell cycle arrest and apoptosis in human breast cancer cells MDA-MB-231 and MCF-7 – a comparative study

Kabała‐Dzik

Rzepecka‐Stojko

Kubina

et al. 2018

Cell Mol Biol (Noisy-le-grand)

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Breast cancer is one of the most common causes of mortality in women. Flavonoids, among other compounds, are bioactive constituents of propolis. In this comparative study, we investigated the effects of flavonoids apigenin (API), genistein (GEN), hesperidin (HES), naringin (NAR) and quercetin (QUE) on the proliferation, apoptosis, and cell cycle of two different human cancer cells-MDA-MB-231, estrogen-negative, and MCF-7, estrogen-positive receptor breast carcinoma cells. Many cytotoxic reports of flavonoids were performed by MTT assay. However, it's reported that MTT is reduced in metabolically active cells and yields an insoluble purple formazan, which indicates that obtained cytotoxic results of flavonoids could be inconsistent. Cell viability was measured by NR, neutral red assay, while the percentage of apoptotic cells and cell cycle arrest were determined by flow cytometry and Muse cell cycle assay, respectively. The results showed a high dose-dependent effect in cell viability tests. IC 50 values were as follows (MCF-7/MDA-MB-231, for 48 h, in µM): 9.39/50.83 for HES, 25.19/88.17 for API, 40.26/333.51 for NAR, 49.49/47.50 for GEN and 95.12/130.10 for QUE. Flavonoid-induced apoptosis was dose-and time-dependent, for both cancer cell lines, though flavonoids were more active on MCF-7 cells. The flavonoids also induced cell cycle arrest in cancer cells.

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Cytotoxicity of trans-chalcone and licochalcone A against breast cancer cells is due to apoptosis induction and cell cycle arrest

Cited by 84 publications

References 28 publications

Licochalcone A suppresses hexokinase 2-mediated tumor glycolysis in gastric cancer via downregulation of the Akt signaling pathway

Licochalcone A suppresses hexokinase 2-mediated tumor glycolysis in gastric cancer via downregulation of the Akt signaling pathway

Antiproliferative activity and p53 upregulation effects of chalcones on human breast cancer cells

Flavonoids, bioactive components of propolis, exhibit cytotoxic activity and induce cell cycle arrest and apoptosis in human breast cancer cells MDA-MB-231 and MCF-7 – a comparative study

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