A bioactive compound isolated from Duku ( Lansium domesticum Corr) fruit peels exhibits cytotoxicity against T47D cell line.

Background: Breast cancer is a major health problem for women globally. Many attempts have been promoted to cure cancer by finding new anticancer medicines from natural resources. Despite the richness of biodiversity discovered, there are some natural resources that remain unexplored. Fruit peels of Duku ( Lansium domesticum Corr.) are rich with compounds that may have the potential to be developed as anticancer drugs. This study aimed to isolate cytotoxic compounds from the fruit peels of L. domesticum and assess their cytotoxic nature against T47D cells. Methods: Powdered peels were macerated with ethyl acetate and the filtrate was evaporated to give EtOAc extract A. Dried extract A was triturated with n-hexane to give n-hexane soluble fraction B and insoluble fraction C. The cytotoxic nature of these three samples were assessed using MTT assay using T47D cells and doxorubicin as a control. Results: Fraction C that showed the smallest IC50 (25.56 ± 0.64μg/mL) value compared to extract A and fraction B. Fraction C was further fractionated by vacuum liquid chromatography to give 6 subfractions. Subfraction 2 showed a single compound based on thin layer chromatography, and this compound was identified as Lamesticumin A on the basis of its spectroscopic data. Lamesticumin A demonstrated cytotoxic activity against T47D cell lines with an IC 50 value of 15.68± 0.30µg/mL. Conclusions: Further research is needed to investigate the potential of the natural compound Lamesticumin A derived from L. domesticum fruit peel as an anticancer therapy.

Background: Breast cancer is a major health problem for women globally. Many attempts have been promoted to cure cancer by finding new anticancer medicines from natural resources. Despite the richness of biodiversity discovered, there are some natural resources that remain unexplored. Fruit peels of Duku ( Lansium domesticum Corr.) are rich with compounds that may have the potential to be developed as anticancer drugs. This study aimed to isolate cytotoxic compounds from the fruit peels of L. domesticum and assess their cytotoxic nature against T47D cells. Methods: Powdered peels were macerated with ethyl acetate and the filtrate was evaporated to give EtOAc extract A. Dried extract A was triturated with n-hexane to give n-hexane soluble fraction B and insoluble fraction C. The cytotoxic nature of these three samples were assessed using MTT assay using T47D cells and doxorubicin as a control. Results: Fraction C that showed the smallest IC50 (25.56 ± 0.64μg/mL) value compared to extract A and fraction B. Fraction C was further fractionated by vacuum liquid chromatography to give 6 subfractions. Subfraction 2 showed a single compound based on thin layer chromatography, and this compound was identified as Lamesticumin A on the basis of its spectroscopic data. Lamesticumin A demonstrated cytotoxic activity against T47D cell lines with an IC 50 value of 15.68 ± 0.30µg/mL. Conclusions: Further research is needed to investigate the potential of the natural compound Lamesticumin A derived from L. domesticum fruit peel as an anticancer therapy.

Lansium domesticum (fam. Meliaceae) contains various compounds with various biological activities. Based on the previous research, extracts from several parts of the plant have biological activity. This study aimed to isolate a compound from the fruitpeel of L. domesticum and evaluate cytotoxic activity against T47D, WiDr and HepG2 cell lines. Powdered peels were macerated with ethyl acetate and the filtrate was evaporated to give EtOAc extract. Dried extract was triturated with n-hexane to give n-hexane soluble fraction (A) and insoluble fraction (B). The fraction B was separated using vacuum column chromatography (VLC) with mobile phase n-hexane: ethyl acetate and given 5 fractions. Fractions B3-B5 were combined and separated using VLC with n-hexane and ethyl acetate as mobile phase. This VLC separation gave 18 subractions, subfractions 6-9 with the similar TLC profile were combined. This subfraction was separated further using preparative thin layer chromatography to give compound 1. The Isolated compound (1) appeared as liquid. The chemical structure of 1 was identified acoording to spectroscopic data and comparison with literature. Cytotoxic bioassay was performed on T-47D, WiDr and Hep G2 cell lines in a series of concentrations at 50, 40, 30, 20, 10 and 5µg/mL, with Doxorubicine used as positive control. According to spectroscopic data, compound 1 was identified as 2-ethyl,3-(1’-hydroxy-2’-menthene) propenal, and demonstrate the strongest cytotoxicity against T-47D cell lines (IC50=39.18+1.54 µg/mL).

Marine algae is known to contain a wide variety of biomedical compounds having pharmaceutical applications. The aim of this research was to evaluate cytotoxic activity and apoptosis induction of Turbinaria decurrens extract on T47D cell lines. Cytotoxic activity test was conducted by using MTT assay whereas detection of apoptosis was evaluated by DNA fragmentations and flow cytometry analysis. The MTT test showed that crude extract had medium cytotoxic activity to T47D, HepG2, and C28 cell lines with IC50 value of 172, againts 360 and 330 µg ml-1, respectively. After solvent partition of crude extract, the cytotoxic activity of n-hexane and ethyl acetate fractions T47D cell increased, the cytotoxic activity of n. hexane and ethyl acetate fractions T47D cell increased with IC50 value of with IC50 43.1 and 51.9 µg ml-1, respectively, whereas IC50 value of methanol fraction was 383.0 µg ml-1. Analysis of DNA fragmentation of T47D cell showed that both n-hexane and ethyl acetate fractions could not fragment DNA as a features of apoptosis. However, flow cytometry analysis by using annexin-V and propidium iodide staining revealed that n-hexane and ethyl acetate fractions could induce apoptosis in T47D cell. This research indicated that Turbinaria decurrens had potency to induce apoptosis in T47D cells.

The aerial parts of Stachys laxa Boiss. and Buhse. from Siah-bishe in Mazandaran province, Stachys trinervis Aitch. and Hemsl. from Karaj in Alborz province, Stachys subaphylla Rech. F. and Stachys turcomanica Trautv. from Golestan province have been collected in May 2008. Total extracts were obtained through MeOH/H2O (80/20) and then partitioned between CHCl3, EtOAc and MeOH. These fractions and total extracts have been investigated for in-vitro cytotoxic activity against the colon carcinoma (HT-29), colorectal adenocarcinoma (Caco-2), breast ductal carcinoma (T47D) and Swiss mouse embryo fibroblast (NIH 3T3) cell lines using MTT assay (3-(4,5-di methyl thiazol-2-yl)-2,5-di phenyltetrazolium bromide). At each cell line, doses of 3.125, 6.25, 12.5, 25, 100, 200, 400 and 800 µg/mL in 1% (v/v) DMSO of all samples were tested. Ethyl acetate and chloroform fractions of Stachys laxa against proliferation of T47D and HT-29 cell lines and chloroform fraction of Stachys subaphylla and Stachys subaphylla ethyl acetate fraction toward T47D cell line exhibited highest cytotoxic activity (IC50 < 50 µg/mL). Ethyl acetate and chloroform fractions of Stachys turcomanica against HT-29 cell line, except methanol fraction of Stachys subaphylla, the other extrcts on T47D cell line, represented moderate cytotoxic activity (IC50 < 70 µg/mL). All fractions of S. trinervis demonstrated no effective cytotoxic activity. IC50 values confirmed that the growth and proliferation of HT-29 and T47D cells were most affected by chloroform and ethyl acetate fractions of Stachys laxa and Stachys turcomanica due to their nonpolar compounds.

Research into plants with anticancer effects is actively encouraged in orderto discover new drugs with lessertoxicity but more potent effects. The aims of study are to evaluate the antioxidant properties and to investigate the cytotoxic activity of Plectranthus amboinicus (Lour.) Spreng. leaves ethyl acetate fractions on HeLa,T47D and MCF7 cell lines. The extract was prepared by graded maceration using n-hexane and ethyl acetate. The ethyl acetate extract was fractionated in vacuum liquid chromatography with n-hexane: ethyl acetate; and ethyl acetate: methanol as mobile phase. Then, the fractions were analyzed with thin layer chromatography (TLC). The free radical scavenging activity was measured by DPPH method, the total flavonoid content was calculated by quercetin equivalent and the absorbance is measured by using UV-Visible spectrophotometry. The cytotoxic activity were determined using MTT assay. The fractions contained 5 sub fractions with same TLC profile. The fractions showed antioxidant activity by DPPH method with different IC50 values, namely: 130 µg/mL(I), 127 µg/mL(II), 137 µg/mL(III), 129 µg/mL(IV), and 124 µg/ mL(V), respectively. The measurement of total flavonoid content showed 118 mg QE/g (I), 50 mg QE/g (II), 207 mg QE/g (III), 56 mg QE/g (IV), and 55 mg QE/g (V). The IC50 of each sub fractions on HeLa cell were 77 µg/mL, 46 µg/mL, 93 µg/mL, 71 µg/mL and 476 µg/mL; for T47D cell were 1621 µg/mL, 111 µg/mL, 128 µg/mL, 150 µg/mL and 209 µg/mL; and for MCF7 were 259 µg/mL, 343 µg/mL, 575 µg/mL, 408 µg/mL and 250 µg/mL. Based on the results, the fractions derived from ethyl acetate extract of Plectranthus amboinicus (Lour.) Spreng. leaves exhibit antioxidant. The Fraction II from ethyl acetate extract of Plectranthus amboinicus (Lour.) Spreng. was the most cytotoxic on HeLa, T47D and MCF7 cell lines. It is potential to undergo further isolation of its cytotoxic compounds.Keywords : antioxidant, cytotoxic, Plectranthus amboinicul (Lour.) Spreng., ethyl acetate fractions

Novel benzenesulfonamides as dual VEGFR2/FGFR1 inhibitors targeting breast cancer: Design, synthesis, anticancer activity and in silico studies

Objective(s):Berberine, a naturally occurring isoquinoline alkaloid, has shown antitumor properties in some in vitro systems. But the effect of berberine on breast cancer has not yet been completely studied. In this study, we evaluated anticancer properties of berberine in comparison to doxorubicin.Materials and Methods:The antiproliferative effects of berberine and doxorubicin alone and in combination were evaluated in T47D and MCF7 cell lines using MTT cytotoxicity assay. In addition, flow cytometry analysis was performed to evaluate the cell cycle alteration and apoptosis induction in these cell lines following exposure to berberine and doxorubicin alone and in combination.Results:The IC50 of berberine was determined to be 25 µM after 48 hr of treatment in both cell lines but for doxorubicin it was 250 nM and 500 nM in T47D and MCF-7 cell lines, respectively. Co-treatment with berberine and doxorubicin increased cytotoxicity in T47D cells more significantly than in MCF-7 cells. Flow cytometry results demonstrated that berberine alone or in combination with doxorubicin induced G2/M arrest in the T47D cells, but G0/G1 arrest in the MCF-7 cells. Doxorubicin alone induced G2/M arrest in both cell lines. Furthermore, berberine and doxorubicin alone or in combination significantly induced apoptosis in both cell lines.Conclusion:Berberine alone and in combination with doxorubicin inhibited cell proliferation, induced apoptosis and altered cell cycle distribution of breast cancer cells. Therefore, berberine showed to be a good candidate for further studies as a new anticancer drug in the treatment of human breast cancer.

The proliferative effects of 5-androstene-3β,17β-diol and 5α-dihydrotestosterone on cell cycle analysis and cell proliferation in MCF7, T47D and MDAMB231 breast cancer cell lines

The compound 2’,4-dihydroxy-3-methoxychalcone and 2’,4’,4-trihydroxy-3-methoxychalcone have been synthesized through Claisen-Schmidt reaction from 2-hydroxyacetophenone and 2,4-dihydroxyacetophenone with 4-hydroxy-3-methoxy benzaldehida (vanillin) in aqueous KOH 40% and KSF montmorillonite as catalyst in methanol. All these products were characterized by FT-IR, TLC Scanner, GC-MS, MS-Direct, and 1H-NMR and 13C-NMR spectrometer. Both of these compounds were tested citotoxycity activity as an anticancer against cervical, colon, and breast cancer cells (Hela, WiDr, and T47D cell lines) using MTT assay in vitro. Dose series given test solution concentration on Hela, WiDr, and T47D cells started from 6,25; 25; 50 and 100 µg/mL with incubation treatment for 24 hours. The result of study showed that the 2’,4-dihydroxy-3-methoxychalcone as bright yellow crystal with the melting point of 114-115 °C and the yield of 13.77% and the 2’,4’,4-trihydroxy-3-methoxychalcone as bright yellow crystals with the melting point of 195-197 °C and the yield of 6%. Other 2’,4-dihydroxy-3-methoxychalcone and 2’,4’,4-trihydroxy-3-methoxychalcone also exhibited cytotoxic activity against the cancer cell lines, with the 2’,4’,4-trihydroxy-3-methoxychalcone showed greater activities than the 2’,4-dihydroxy-3-methoxychalcone in WiDr cell lines. The 2’,4-dihydroxy-3-methoxychalcone and 2’,4’,4-trihydroxy-3-methoxychalcone exhibited strong anticancer activities with IC50 value below 20 µg/mL. The activity of 2’,4’,4-trihydroxy-3-methoxychalcone showed the most active against Hela and WiDr cell lines with IC50 value 8.53 and 2.66 µg/mL respectively, than T47D cell lines with IC50 value 24.61 µg/mL. The test results cytotoxic of 2’,4-dihydroxy-3-methoxychalcone showed the most active against Hela and WiDr cell lines with IC50 value 12.80, 19.57 µg/mL than T47D cell lines with IC50 value of 20.73 µg/mL. IC50 value indicated that 2’,4-dihydroxy-3-methoxychalcone and 2’,4’,4-trihydroxy-3-methoxychalcone potential as inhibitors in Hela, WiDr and T47D cell lines.

People on Timor island use Faloak (Sterculia quadrifida R.Br.) bark as herbal remedy to cure diseases such as liver diseases, gastroenteritis and as stamina booster. This study aims to analyze the ability of anticancer fraction of faloak bark ethanol extract. The mashed bark of faloak plants extracted by maceration method using ethanol. The ethanol extract fractionated using preparative thin layer chromatography with mixture mobile phase which, chloroform, n-butanol, ethyl acetate with ratio (3: 4: 1,5). Chromatogram detected with visible light, UV254, UV366, and cerium sulfate reagent, then marked. Fraction obtained five fractions. Cytotoxic test against T47D cell and Vero cell conducted using MTT, IC50 and selectivity sndex (SI) used as an anticancer efficacy parameter. Fraction 4 showed moderate anticancer activity with IC50 of 21.89 μg/mL in T47D cell line. Keywords: Faloak bark, anticancer activiy, T47D cell line

Driven by the urgent need for novel anticancer agents capable of overcoming limitations associated with conventional therapies, a new series of benzo[b]oxepine derivatives featuring 1,3,4-thiadiazole (5a-5k) linkers was successfully produced through a Vilsmeier-Haack reaction, thiazole formation, and C─N cross coupling or an Ullmann-type coupling reaction with the corresponding hydrazides. The structure of the synthesized compounds was confirmed through various spectroscopic techniques, such as NMR (1H/13C) and HRMS. The cytotoxic activity of the newly synthesized congeners was investigated against MCF-7, MDA-MB-231, and T-47D (human breast cancer), A549, and PC-9 (lung cancer) cell lines. It is worth noting that the half maximal inhibitory concentration (IC50) value of 5i against MDA-MB-231 cells was 3.50 ± 1.03µg mL-1, which was obviously superior to that of etoposide (4.03 ± 1.10µg mL-1). From the screening results, thiadiazole analogues 5a-5k showed excellent inhibitory activity against lung carcinoma in the range of IC50 values 4.79 ± 1.14 to 40.86 ± 0.93µg mL-1. In this series, analogues 5a, 5i, and 5j show a remarkable antiproliferative profile on the T-47D cell line with IC50 values of 5.70 ± 0.90, 4.25 ± 0.76, and 4.12 ± 1.35µg mL-1 by using etoposide as a standard, whose IC50 is 5.65 ± 0.35µg mL-1. Moreover, molecules 5f, 5i, and 5j demonstrated the highest docking scores of -8.83, -8.93, and -9.20kcal mol-1 in in silico tests conducted on the most potent compounds. These therefore displayed the most hydrophobic, electrostatic, and hydrogen bonding with the estrogen receptor complex in breast cancer (PDB: 5T1Z) because of their highest docking score. Extending our exploration, an analysis of the ADME-Tox profiling confirmed the safe use of these newly synthesized scaffolds, paving the way for promising therapeutic applications in the field of anticancer therapy. Additionally, DFT analysis identified electron-rich and electron-deficient areas on molecules, which were utilized in docking studies to compare polar and non-polar interactions with kinase. Collectively, these findings underscore the potential of 1,3,4-thiadiazole hybrids, particularly compounds5i and 5j, as promising leads for the development of new anticancer agents.

Mekai (Albertisia papuana Becc.) root is usually used for the treatment of various diseases especially cancer by Dayak people, Kalimantan. The objective of this study was to evaluate the cytotoxic activities of A. papuana Becc. root extract and its fractions on breast cancer cell lines (T47D) and normal cell lines (Vero). The plant roots were macerated using ethanol. The MTT assay was applied to determine the cytotoxic activity of ethanol extract on T47D and Vero cell lines. Moreover, SPSS (Probit analysis) was used for calculating IC50 extract. The ethanol root extract was fractionated using vacuum liquid chromatography. The same method was used for determined the cytotoxic activities and of IC50 of the fractions. The result showed that the ethanol extract less toxic on T47D cell lines less toxic than ethyl acetate : ethanol (2:3 v/v) fractions that have IC50 21.3 µg · mL−1 and 9.1 µg · mL−1 respectively. The IC50 values of ethanol extract and ethyl acetate : ethanol (2:3 v/v) fraction on Vero cell lines were 233.0 µg · mL−1 (SI = 11) and 42.5 µg· mL−1 (SI = 5), respectively. Both of those two solutions were toxic to breast cancer cell lines T47D but not to Vero cell lines.

Today, attempt to the preparation of stable drug with high drug delivery efficiency is inevitable. Curcumin (diferuloylmethane), with hydrophobic structure obtained from the herb of Curcuma longa , have various applications in cancer therapy. But, its low water solubility and bioavailability is possible for poor drug delivery of curcumin . In this study, we prepared β-cyclodextrin- curcumin complex to determine the inhibitory effect of this drug on telomerase gene expression. Curcumin was encapsulated into cyclodextrin and the rate of curcumin loading was estimated. Cytotoxic effects of β-cyclodextrin curcumin were investigated by colorimetric cell viability (MTT) assay. Then inhibition of telomerase gene expression was determined by real-time polymerase chain reaction (PCR). MTT assay demonstrated that β-cyclodextrin have no cytotoxic effect on its own. Also, it showed dose-dependency and time-dependency for β-cyclodextrin– curcumin on T47D cell line. Expression of telomerase gene in cells effectively was reduced as the concentration of β-cyclodextrin – curcumin complex was increased. The results show that β-cyclodextrin - curcumin complex have cytotoxic effect on T47D cell line through down regulation of telomerase expression and induction apoptosis by enhancing curcumin uptake by cells. So, β-cyclodextrin could be good carrier for these kinds of hydrophobic agents. Key words: Anti cancer drug, target therapy, telomerase, breast cancer, drug delivery

Breast cancer is one of cancer with high mortality. This cancer not only attacks women, but also men. Indonesia has many plants which potential as anticancer, such as orchids. Spathoglottis plicata is one of the orchid species that abundant in Indonesia and has a lot of antioxidant compounds which is guessed have anticancer properties. The objectives of this study were to study the cytotoxic activity and IC50 value of aquadest, ethanolic, and chloroform extracts of S. plicata’s pseudobulbs, leaves, and whole plants on T47D cells (breast cancer cells line) as well as cytotoxic activity of the specific fraction of the most toxic crude extract. S. plicata used in this study was obtained from Bungarinte nursery. Extractions were done by maceration method using aquadest, ethanol, and chloroform as the solvent. Cytotoxic test on T47D cells were done by MTT assay. The cytotoxic data were analyzed using one-way ANOVA followed by Tukey’s HSD test. The IC50 of each extracts were calculate by probit analysis. The lowest IC50 value among all extracts was fractionated and isolated by preparative TLC. The cytotoxic activity and IC50 of this fractions were analyzed. The results showed that only 2 from 9 crude extracts that able to calculate its IC50 because those two extracts have concentration dependent pattern of inhibition concentration. Chloroform extract have the lowest IC50 value (369,837 μg/mL). Then, this extract fractionated by eluen n-hexane : ethyl acetate 4:1. Four fractions were collected. The lowest IC50 value is fraction IV (144,41 μg/mL). Based on the results it could be concluded that S. plicata leaves have moderate potency to develop as anticancet agents, especially on breast cancer. Keywords: S. plicata, T47D cells, cytotoxic, MTT assay, preparative TLC.