Cytotoxic activity and apoptosis induction of 8-hydroxyisocapnolactone-2´,3´-diol and its combination with Doxorubicin on MCF-7 and T47D cells

2021 ◽  
Vol 18 (1) ◽  
pp. 9-22
Author(s):  
Joko Kristianto ◽  
Haryoto Haryoto ◽  
Peni Indrayudha

Mangrove plants as traditional medicine have long been used by the society for the therapy of anticancer diseases. So far, the potency of mangrove plants as anticancer has not been studied intensively. The methanol extract of R. mucronata stem bark has cytotoxic activity on myeloma cells. This study aims to determine the isolates of the ethyl acetate fraction of the methanol extract of the stem bark of R. mucronata and R. apiculata, and to examine the potency of cytotoxic activity against MCF-7 and T47D cells. The powder of the stem bark of R. mucronata and R. apiculata were extracted with methanol by maceration, and then the methanol extract was fractionated consecutively using n-hexane, ethyl acetate, and methanol. Ethyl acetate fraction was then purified by column chromatography with a diameter of 2 cm and a height of 30 cm with a static phase in the form of silica gel 60 (0.063-0.2 mm) Merck 7734 and eluent n-hexane:ethyl acetate (6: 4, 5: 5, 6: 4, 7: 3, 8: 2, 9: 1) and n-hexane: methanol (9,5: 0,5) 10 ml each. The eluates that produce the same number and pattern of stains were combined into one isolate. Then the eluate was evaporated at room temperature. Then the purification results of the extract R. mucronata were isolated using preparative TLC with 0.25 mm GF254 silica gel as static phase and n-hexane mobile phase: ethyl acetate (6: 4), while the apiculata extract with n-hexane mobile phase: ethyl acetate (5: 5). The results of the stain separation of the compound were scraped off and separated from the static phase using a solvent. The purity of isolates compound was examined using TLC in the static phase of silica gel GF254 0.25 mm. The qualitative test results of the ethyl acetate fraction of R. apiculata stem bark with an NMR spectrophotometer showed a composition of cis-3- (3,5-dihydroxyphenyl) acrylic acid, while the ethyl acetate fraction of R. mucronata stem bark contained n-hexan-3-ol compounds. The cytotoxicity test of ethanol extract, n-hexane fraction, ethyl acetate fraction and ethanol extract was carried out on MCF-7 and T47D cells using the MTT method. The results proved that the ethanol extract, n-hexane fraction, ethyl acetate fraction and ethanol fraction from the ethanol extract of R. mucronata and R. apiculata stem bark, based on cytotoxic activity, were inactive against MCF-7 and T47D cells.


2020 ◽  
Vol 20 (4) ◽  
pp. 766
Author(s):  
Muhammad Sulaiman Zubair ◽  
Walied Mohamed Alarif ◽  
Mohamed Ali Ghandourah ◽  
Syariful Anam ◽  
Ibrahim Jantan

Benalu batu (Begonia sp.) had been used traditionally as an anticancer medicinal plant by Wana tribe in Morowali, Central Sulawesi, This study aims to evaluate the cytotoxic activity of 2-O-β-glucopyranosil cucurbitacin D, isolated from the ethyl acetate soluble fraction of Benalu batu (Begonia sp.) and to determine its action on apoptosis induction. Benalu batu (Begonia sp.) herb was extracted by maceration using ethanol 96% as a solvent. Vacuum liquid column chromatography and preparative thin layer chromatography have been applied on fractionation and isolation of the compound. The structure elucidation was performed by extensive analysis of 1D/2D nuclear magnetic resonance (NMR) and Mass Spectrophotometer (MS). Cytotoxic activity against human breast adenocarcinoma (MCF-7) and human colon colorectal carcinoma (HCT-116) cell lines were performed by 5-diphenyltetrazolium bromide (MTT) method. Annexin V-FITC assay was employed to determine the apoptosis induction. 2-O-β-glucopyranosil cucurbitacin D showed potent cytotoxic activity against MCF-7 and HCT-116 with the IC50 of 19.913 and 0.002 μg/mL, respectively. Annexin V-FITC assay clearly exhibited the cytotoxic mechanism on MCF-7 and HCT-116 via apoptosis induction with a significant percentage of early and late apoptosis of 75.8 and 78.4%, respectively. This study reveals the potential cytotoxic activity of 2-O-β-glucopyranosil cucurbitacin D isolated from Benalu batu and its mechanism via apoptosis induction.


2018 ◽  
Vol 8 (3) ◽  
pp. 159 ◽  
Author(s):  
Meghan Fragis ◽  
Abdulmonem I. Murayyan ◽  
Suresh Neethirajan

Background: Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths among Canadian women. Cancer management through changes in lifestyle, such as increased intake of foods rich in dietary flavonoids, have been shown to decrease the risk associated with breast, liver, colorectal, and upper-digestive cancers in epidemiologic studies. Onions are high in flavonoid content and one of the most common vegetables. Additionally, onions are used in most Canadian cuisines.Methods: We investigated the effect of five prominent Ontario grown onion (Stanley, Ruby Ring, LaSalle, Fortress, and Safrane) extracts on two subtypes of breast cancer cell lines: a triple negative breast cancer line MDA-MB-231 and an ER+ breast cancer line MCF-7.Results: These onion extracts elicited strong anti-proliferative, anti-migratory, and cytotoxic activities on both the cancer cell lines. Flavonoids present in these onion extracts induced apoptosis, cell cycle arrest in the G2/M phase, and a reduction in mitochondrial membrane potential at dose-dependent concentrations. Onion extracts were more effective against MDA-MB-231 compared to the MCF-7 cell line. Conclusion: In this study, we investigated the extracts synthesized from Ontario-grown onion varieties in inducing anti-migratory, cytostatic, and cytotoxic activities in two sub-types of human breast cancer cell lines. Anti-tumor activity of these extracts depends upon the varietal and can be formulated into nutraceuticals and functional foods for the wellbeing of cancer patients. Overall, the results suggest that onion extracts are a good source of flavonoids with anti-cancerous properties.Keywords: onion extracts; flavonoids; anti-proliferative; breast cancer; cytotoxic activity


2019 ◽  
Vol 35 (6) ◽  
pp. 108-113
Author(s):  
J.A. Makarova ◽  
A.A. Poloznikov

A method to assess the apoptosis level in cell models based on the analysis of the expression of micRNAs located in introns of apoptosis genes has been developed. Bioinformation analysis identified 536 genes associated with apoptosis; 30 of them contained 38 pre-microRNAs encoding 41 mature microRNAs. A significant change in the expression of hsa-miR-1244 and hsa-miR-4479 in response to apoptosis induction in the MCF-7 breast cancer cell line was revealed. A correlation was also found between the expression level of these miRNAs and the size of the primary tumor (process stage) in patients with breast cancer. apoptosis, microRNA, MCF7, breast cancer This work was supported by the Ministry of Education and Science of the Russian Federation (Project no. RFMEFI61618X0092).


Author(s):  
Zeinab Abedian ◽  
Niloofar Jenabian ◽  
Ali Akbar Moghadamnia ◽  
Ebrahim Zabihi ◽  
Roghayeh Pourbagher ◽  
...  

Objective/ Background: Cancer is still the most common cause of morbidity in world and new powerful anticancer agents without severe side effects from natural sources is important. Methods: The evaluation of cytotoxicity and apoptosis induction was carried out in MCF-7,HeLa and Saos-2 as cancerous cell lines with different histological origin and human fibroblast served as control normal cell. The cells were treated with different concentrations of chitosan and the cytotoxicity was determined using MTT assay after 24, 48 and 72 h .The mode of death was evaluated by flow cytometry . Results: While both types of chitosan showed significant concentration-dependently cytotoxic effects against the three cancerous cell lines, fibroblast cells showed somehow more compatibility with chitosan. On the other hand, there were no significant differences between LMWC and HMWC cytotoxicity in all cell lines. The flow cytometry results showed the apoptosis pattern of death more in Saos-2 and HeLa while necrosis was more observable with MCF7. Also higher viability with both types of chitosan was seen in fibroblast as normal cells Conclusion: Chitosan shows anticancerous effect against 3 cancerous cell lines, while it is compatible with normal diploid fibroblast cells. Furthermore, it seems that the molecular weight of chitosan does not affect its anticancerous property.


2020 ◽  
Vol 10 (3) ◽  
pp. 257-261
Author(s):  
Tati Herlina ◽  
Merlin ◽  
Mohd. Azlan ◽  
Unang Supratman

Background: Erythrina poeppigiana (Leguminosae) is a high-growing plant with an orange flower that is widely distributed in tropical and subtropical countries. This particular plant is widely used in traditional medicine for gynecological complications and the treatment of various diseases. There exists no previous information regarding cytotoxic compounds from this plant. Objective: This research is to isolate cytotoxic compounds from E. poeppigiana. Methods: The isolation step was carried out using a combination of chromatographic techniques to obtain isolated three compounds (1, 2, and 3). Results: The chemical structure of isolated compounds was elucidated by spectroscopic methods and identified as β-erythroidine (1), 8-oxo-β-erythroidine (2), and 8-oxo-α-erythroidine (3). Compounds (1-3) showed cytotoxic activity against MCF-7 breast cancer line with IC50 values of 36.8, 60.8 and 875.4 μM, respectively. Conclusion: Three compounds have been successfully isolated from Erythrina poeppigiana (Leguminosae), showing cytotoxic properties against MCF-7 breast cancer line. Structure-activity relationship studies showed that the presence of enone moiety on compound 1 can reduce its cytotoxic activity towards MCF-7 breast cancer line.


2021 ◽  
Vol 11 (11) ◽  
pp. 5300
Author(s):  
Jozef Hudec ◽  
Jan Mojzis ◽  
Marta Habanova ◽  
Jorge A. Saraiva ◽  
Pavel Hradil ◽  
...  

Sarcopoterium spinosum (L.) is a medicinal plant traditionally used for the treatment of various diseases including cancer in the Near- and Middle East. The fractions and constituents of the ethanol extract of S. spinosum were screened for in vitro cytotoxic activities on Jurkat (acute T-lymphoblastic leukemia), HeLa (cervical adenocarcinoma), MCF-7 (mammary gland adenocarcinoma), Caco-2 (human colorectal adenocarcinoma), and MDA-MB-231 (mammary gland adenocarcinoma) cell lines using the MTT (3-(dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The ethanol extract was subsequently re-extracted with ethyl acetate and in its sub-fraction obtained by column chromatography three compounds (stachydrine, benzalkonium chloride and rutine) were the first time identified by nuclear magnetic resonance (NMR) analyses. The most active subfraction showed cytotoxic activity against HeLa, MCF-7, and Caco-2 cell lines. The three compounds mentioned, as standards of high-performance liquid chromatography (HPLC) quality, were studied individually and in combination. Cytotoxic activity observed might be due to the presence of benzalkonium chloride and rutin. Benzalkonium chloride showed the strongest growth suppression effect against HeLa cells (IC50 8.10−7 M) and MCF-7 cells (IC50 5.10−6 M). The mixture of stachydrine and benzalkonium chloride allowed a synergistic cytotoxic effect against all tested cancer and normal cells to be obtained. Anti-cancer activity of the plant extract of S. spinosum remains under-investigated, so this research describes how the three major compounds identified in the ethyl acetate extract can exert a significant dose dependent in vitro cytotoxicity.


2021 ◽  
Vol 16 (2) ◽  
pp. 1934578X2199334
Author(s):  
Do Thi Trang ◽  
Bui Huu Tai ◽  
Dan Thuy Hang ◽  
Pham Hai Yen ◽  
Phan Thi Thanh Huong ◽  
...  

Seven compounds (1-7) were isolated from the marine sponge Aaptos aaptos living in the Vietnamese sea. Their structures were determined as 2 hours, 5 H,7 H,9 H-9 S-hydroxy-imidazo[1,5- α]pyridine-1,3-dione (1), 3-([9-methylhexadecyl]oxy)propane-1,2-diol 2, 2,3-dihydro-2,3-dioxoaaptamine (3), indol-3-aldehyde (4), methyl indole-3-carboxylate (5) 4-hydroxy-5-(indole-3-yl)−5-oxo-pentan-2-one (6), and thymidine (7) by extensive analysis of HR-ESI-MS, 1D, and 2D NMR spectral data, as well as by comparison of the spectral data with those reported in the literature. In addition, the absolute configuration of 1 was determined from the experimental ECD spectrum and comparison of this with the theoretical ECD calculations using the TDDFT method. Compounds 1 and 2 were isolated from nature for the first time. Compound 3 induced cytotoxic activity against SK-LU-1, MCF-7, HepG2, and SK-Mel-2 cell lines with IC50 values of 41.27 ± 2.63, 40.70 ± 2.65, 34.31 ± 3.43, and 36.63 ± 1.40 µM, respectively.


2021 ◽  
Author(s):  
Jesica M. Ramírez-Villalobos ◽  
César I. Romo-Sáenz ◽  
Karla S. Morán Santibañez ◽  
Patricia Tamez-Guerra ◽  
Ramiro Quintanilla-Licea ◽  
...  

Abstract Background: Arid zone plants such as cacti are known to harbor diverse groups of endophytic fungi, which represent potential sources of new compounds with anticancer properties. In the present study we isolated, identified, and characterized Pachycereus marginatus (DC.) Britton & Ros endophytic fungi with cytotoxic activity against murine and human tumor cell lines.Methods: Endophytic fungi were isolated from P. marginatus stems. Methanol extracts were then obtained from fungi liquid cultures and their cytotoxic activity at concentrations ranging from 31 µg/ml to 250 µg/ml against murine L5178Y-R lymphoma, human colorectal adenocarcinoma HT-29, and human breast cancer MCF-7 was evaluated by the colorimetric 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide reduction assay, using the normal cells Macacus rhesus monkey epitelial kidney MA-104 and human peripheral blood mononuclear cells (PBMC) as controls. IC50 values were obtained and the selectivity index (SI) was calculated from the IC50 ratio of cancer cells and normal cells. Furthermore, molecular identification of fungi showing cytotoxic activity was determined by the internal transcribed spacer molecular marker.Results: The Cladosporium sp. PME-H008 strain showed significant (P < 0.01) 94.3% and 36.8% cytotoxicity against L5178Y-R and HT-29 cells, respectively. The highest SI was observed by L5178Y-R cells with 2.4 and 2.9 for MA-104 and PBMC respectively. In addition, the Metarhizium anisopliae PME-H007 strain was more effective against MCF-7 with 55.8% cytotoxicity. The lowest IC50 was obtained with the Aspergillus sp. PME-H005 strain at 95.21 µg/ml against the MCF-7 cell line, followed by PME-H008 strain at 101 µg/ml against L5178Y-R cells.Conclusion: P. marginatus endophytic fungi showed in vitro cytotoxic activity against murine and human tumor cell lines, without affecting normal cells.


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