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Sulfated polysaccharides derived from marine microalgae, Synechococcus sp. VDW, inhibit the human colon cancer cell line Caco-2 by promoting cell apoptosis via the JNK and p38 MAPK signaling pathway
(2023-01-01)
Srimongkol, Piroonporn
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Songserm, Pajareeya
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Kuptawach, Kittisak
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Puthong, Songchan
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Sangtanoo, Papassara
This study offers an examination of the physicochemical qualities of marine microalgae-derived sulfated polysaccharides (MMPS) from Synechococcus sp. VDW along with an investigation of their antioxidant and antitumor activities. On average, MMPS offered a molecular weight of 190.94 kDa with sulfate content of 16.83 %. There were shown to be four different monosaccharides contained within MMPS. The anticancer characteristics of human colon cancer cell lines (Caco-2) were also investigated. Flow cytometry revealed that MMPS triggered apoptosis at doses of 1 mg mL−1. Meanwhile, analysis of gene and apoptosis protein expression demonstrated that MMPS increased apoptosis in Caco-2 cells via the p38 MAPK and JNK signaling pathways. These findings contribute to our current understanding of how MMPS helps promote tumor suppression. In conclusion, the possibility that MMPS may possess anticancer qualities in the treatment of human colon cancer makes it an appealing candidate for anticancer polysaccharide combinations with chemotherapeutic agents and functional foods.
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4-Aryl-N-phenylpyrimidin-2-amines targeting EGFR-tyrosine kinase attenuated EGFR-expressing cell lines
(2022-08-01)
Tabtimmai, Lueacha
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Supakun, Prapasri
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Toviwek, Borvornvat
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Jiwacharoenchai, Nattanan
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Kiriwan, Duangnapa
Target therapies have been widely developed to combat various diseases and cancer. Epidermal Growth Factor Receptor is still a currently therapeutic target for solid tumor. Aberration of EGFR activity or expression reflect disease progression and poor prognosis. Recently, several newly synthesized 4-aryl-N-phenylpyrimidin-2-amines with some modifications at R2 selectively elicited cytotoxicity against A549. Therefore, harboring EGFR expression would be reasonable for the assessment. Herein, the 4-aryl-N-phenylpyrimidin-2-amines derivatives; N-(3-{[4-(4-methoxyphenyl) pyrimidin-2-yl]amino}phenyl), 3-{[4-(3-methoxyphenyl) pyrimidin-2-yl] amino}benzene-1-sulfonamide. (13g), methanesulfonamide (13c), 3-[(4-phenylpyrimidin-2-yl)amino] benzene-1-sulfonamide (13f) and 3-(benzene-1-sulfonamide) (5) were selected as promising derivatives for targeted-EGFR analysis. Kinase enzymatic-based assay exhibited IC<inf>50</inf> values of 5.61, 31.92, 73.80 and 0.79 nM of each derivative, respectively whilst 41.50 nM of Gefitinib. Molecular docking deciphered the mode of binding of each derivative in ATP-binding site greater than gefitinib. Although, (13g) demonstrated the highest binding free energy among the other but not in ATP-binding site as the others does that related to its IC<inf>50</inf> values. (13c), (13f), and (5) therefore were subjected for cell-based analysis. A549 and A431 were used as wtEGFR-expressing cells for cell-based assay. (13c), (13f), and (5) had high toxicity towards in both cells while (5) had much more toxicity on A431. (13c), (13f) and (5) not only induced apoptosis in a dose-dependent manner but reduced clonogenic formation greater than gefitinib. Migration of EGF-stimulated A431 was significantly delayed by the compounds over time but they could not delay EGF-stimulated A549 migration. Taken together, (13c), (13f) and (5) would be a newly synthesized derivative by targeting wtEGFR-expressing cells that attenuated EGFR-driven cancer hallmark leading to targeted therapy development.
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Suppression of PI3K/Akt/mTOR pathway in chrysoeriol-induced apoptosis of rat C6 glioma cells
(2022-01-01)
Wongkularb, Suppanut
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Limboonreung, Tanapol
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Tuchinda, Patoomratana
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Chongthammakun, Sukumal
Chrysoeriol, a dietary methoxyflavonoid which is found in tropical medicinal plants, has been shown to have antioxidant, anti-inflammatory, and antineoplastic properties. The present study aimed to investigate the effects of chrysoeriol and its related mechanisms in rat C6 glioma cells. Cell viability in rat C6 glioma cells were measured by MTT assay. The protein expression levels of cleaved caspase-3, caspase-3, pro-apoptotic (Bax), anti-apoptotic protein (Bcl-2), and Annexin V were detected by Western blot analysis and immunocytochemical staining. Results showed that chrysoeriol significantly decreased cell viability and induced apoptosis in rat C6 glioma cells. Chrysoeriol significantly increased the levels of Bax/Bcl-2 ratio and cleaved caspase-3/caspase-3 ratio. Moreover, treatment with chrysoeriol significantly reduced the phosphorylation of PI3K, Akt, and mTOR expression in ratios. These results suggest that chrysoeriol promote apoptosis in rat C6 glioma cells via suppression of the PI3K/Akt/mTOR signaling pathway, thereby demonstrating the potential antineoplastic effects of chrysoeriol on glioma cells.
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Titania nanosheet generates peroxynitrite-dependent S-nitrosylation and enhances p53 function in lung cancer cells
(2021-08-01)
Soonnarong, Rapeepun
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Tungsukruthai, Sucharat
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Nutho, Bodee
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Rungrotmongkol, Thanyada
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Vinayanuwattikun, Chanida
Metal nanomaterials can enhance the efficacy of current cancer therapies. Here, we show that Ti<inf>0.8</inf> O<inf>2</inf> nanosheets cause cytotoxicity in several lung cancer cells but not in normal cells. The nanosheet-treated cells showed certain apoptosis characteristics. Protein analysis further indicated the activation of the p53-dependent death mechanism. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analyses revealed the cellular uptake of the nanosheets and the induction of cell morphological change. The nanosheets also exhibited a substantial apoptosis effect on drug-resistant metastatic primary lung cancer cells, and it was found that the potency of the nanosheets was dramatically higher than standard drugs. Ti<inf>0.8</inf> O<inf>2</inf> nanosheets induce apoptosis through a molecular mechanism involving peroxynitrite (ONOO−) generation. As peroxynitrite is known to be a potent inducer of S-nitrosylation, we further found that the nanosheets mediated the S-nitrosylation of p53 at C182, resulting in higher protein-protein complex stability, and this was likely to induce the surrounding residues, located in the interface region, to bind more strongly to each other. Molecular dynamics analysis revealed that S-nitrosylation stabilized the p53 dimer with a ∆Gbindresidue of <−1.5 kcal/mol. These results provide novel insight on the apoptosis induction effect of the nanosheets via a molecular mechanism involving S-nitrosylation of the p53 protein, emphasizing the mechanism of action of nanomaterials for cancer therapy.
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Free radical scavenging properties and induction of apoptotic effects of fa fraction obtained after proteolysis of bioactive peptides from microalgae synechococcus sp. VDW
(2019-01-01)
Suttisuwan, Rutairat
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Phunpruch, Saranya
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Saisavoey, Tanatorn
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Sangtanoo, Papassara
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Thongchul, Nuttha
This study aims to determine the antioxidant activity of bioactive peptides derived from Synechococcus sp. VDW cells cultured for 21 days. Synechococcus sp. VDW protein hydrolysates were prepared with trypsin and purified by ultrafiltration with molecular mass cut-off membranes of 10, 5 and 3 kDa. The M<3 kDa (FA) fraction had the highest 2,2'-azino- bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities, with IC50 values of (11.5±0.3) and (13.6±0.2) μg/ mL, respectively. The FA fraction was separated by reversed phase HPLC to yield four subfractions (F1-4). The F4 subfraction showed the highest maximum ABTS radical scavenging activity (3.55±0.61) % and it was selected for further analysis by electrospray ionisation quadrupole time-of-flight mass spectrometry (ESI-Q-TOF-MS/MS) based on de novo peptide sequencing. Five antioxidant peptides were identified, of which AILESYSAGKTK had the highest ABTS radical scavenging activity. Furthermore, the FA fraction showed high cytotoxic activities against human cancer-derived cell lines, especially the colon cancer cell line (SW620) with an IC50 value of (106.6±21.5) μg/mL, but not the untransformed Wi38 cell line. The FA fraction activated the apoptotic pathway in SW620 cells after treatment for 24, 48 and 72 h, with the highest activities of caspases-3, -8 and -9 being observed after treatment for 72 h. These findings suggested that microalgae Synechococcus sp. VDW may be used to develop natural anticancer drugs.

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