Anti-Proliferative Activity and Apoptosis Induction of an Ethanolic Extract of Boesenbergia pandurata (Roxb.) Schlecht. against HeLa and Vero Cell Lines

Rhizomes of Boesenbergia pandurata (Roxb.) Schlecht have been reported to contain active compounds with anticancer properties. This research was carried out to examine anti-proliferative and apoptotic induction against HeLa and Vero cells-line. Dried powder of B. pandurata rhizomes was extracted by a maceration method using 90% ethanol. Cytotoxic assays to determine IC50 and anti-proliferative effects were carried out by MTT methods. Observation of apoptosis was achieved with double staining using acridine orange and ethidium bromide. The results showed that ethanolic extract of B. pandurata was more cytotoxic against HeLa cells (IC50 of 60 μg/ mL) than Vero cells (IC50 of 125 μg/mL). The extract had higher anti-proliferative activity as well as apoptotic induction in HeLa than Vero cells. Therefore, it was concluded that the ethanolic extract of B. pandurata had anti-proliferative as well as apoptosis induction activity dependent on the cell type.     

Antitumor Constituents from Anthriscus Sylvestris (L.) Hoffm

Bioassay-guided chemical investigation of the roots of Anthriscus sylvestris (L.) Hoffm. resulted in theisolation of nine compounds, whose structures were determined by spectroscopic methods. Compound 1 wasisolated from this plant for the first time and compounds 3 and 9 were first found from this genus. Differentpolar fractions of A. sylvestris extract and compounds 1, 6-8 and 9 were evaluated for antitumor activities againstHepG2 (human hepatocellular carcinoma), MG-63 (human osteosarcoma cells), B16 (melanoma cells) and HeLa(human cervical carcinoma cells) lines by the MTT method. The petroleum ether fraction of A. sylvestris extractexhibited excellent inhibitory activity with an IC50 value of 18.3 μg/ml. Among the isolates from the petroleumether fraction, compound 7 showed significant inhibition against the growth of the four tumor cells with IC50values ranging from 12.2-43.3 μg/ml.     

Pyrophen Produced by Endophytic Fungi Aspergillus sp Isolated from Piper crocatum Ruiz & Pav Exhibits Cytotoxic Activity and Induces S Phase Arrest in T47D Breast Cancer Cells

Ethyl acetate extracts obtained from culture of endophytic fungi Aspergillus sp isolated from Piper crocatum Ruiz & Pav, have been shown to possess cytotoxic activity against T47D breast cancer cells. Investigations were here conducted to determine bioactive compounds responsible for the activity. Bioassay guided fractionation was employed to obtain active compounds. Structure elucidation was performed based on analysis of LC-MS, 1H-NMR, 13C-NMR, COSY, DEPT, HMQC, HMBC data. Cytotoxity assays were conducted in 96 well plates against T47D and Vero cell lines. Bioassay guided isolation and chemical investigation led to the isolation of pyrophen, a 4-methoxy-6-(1’-acetamido-2’-phenylethyl)-2H-pyran-2-one. Further analysis of its activity against T47D and Vero cells showed an ability to inhibit the growth of T47D cells with IC50 values of 9.2 μg/mL but less cytotoxicity to Vero cells with an IC50 of 109 μg/mL. This compound at a concentration of 400 ng/mL induced S-phase arrest in T47D cells.     

Sida rhombifolia Exerts Anti-Proliferative and Pro-Apoptotic Effects in Human Liver Cancer HepG2 Cells in Vitro

Purpose: Modern research revealed that plants belonging to the Sida rhombifolia family (Malvaceae) contain biologically active compounds that make them prone to discovering and developing anticancer drugs. This study aimed to evaluate the apoptosis effects of S. rhombifolia extracts in HepG2 Cell Line was performed. Methods: The extractions were prepared, and an MTT assay was applied to evaluate its role in decreasing the viability of HepG2 and HFF cells. Phenolic compounds were analyzed using High-performance liquid chromatography (HPLC). FlowCytometry and RT-qPCR evaluated apoptosis was performed to measure the mRNA expression of pro-and anti-apoptotic mediators. Results: The results can be summarized as EtOAc extract was more cytotoxic against the HepG2 cells (IC50= 364.3 µg/mL) compared to MeOH and HEX extracts (720.2 µg/mL) (560.4 µg/mL) with less cytotoxicity in HFF cells (353.2 µg/mL). The HPLC analysis results revealed most phenolic compounds, such as Epicatechin(1.3 mg/g). The EtOAc extract (300 μg/mL) induced 34% apoptosis in HepG2 cells. RT-qPCR data showed upregulation of the proapoptotic gene (Bax) and increased Bax/BCL-2 ratio by S. rhombifolia EtOAc extract (300 μg/mL). Conclusion: In conclusion, the EtOAc extract of S. rhombifolia is capable of inducing apoptosis in HepG2 cells through modulation of the mitochondrial pathway, which explains their antitumor activity.     

The Cytotoxic,Apoptotic Induction,and Cell Cycle Arrest Activities of Solanum nigrum L. Ethanolic Extract on MCF-7 Human Breast Cancer Cell

Objective: The purpose of this research was to evaluate the cytotoxic, cell cycle arrest, and apoptotic induction activities of the fruit of S. nigrum L. ethanolic-70% extract against MCF-7 human breast cancer cell. Methods: S. nigrum L. ripe fruit was blended and macerated with ethanol 70% and the filtrate was evaporated. The semisolid extract was then analyzed phytochemically. Cytotoxic analysis was performed using MCF-7 cancer and Vero normal cell by MTT method and followed by apoptotic and cell cycle arrest analysis using flow cytometry. Results: The phytochemical analysis resulted that extract contained total phenolic and flavonoid compounds with the level of 1.545±0.080% and 0.212±0.002%, respectively. Glycitin was the highest level of isoflavone compound, namely, 375.0844 mg/100 g extract. The cytotoxic evaluation revealed that the extract exhibited a selectively toxic effect between cancer and normal cell. The extract inhibited MCF-7 proliferation with IC50 value about 40.77±4.86 μg/mL and conversely toward Vero cell at lower cytotoxic activity with an IC50 value of 298.96±27.28 μg/mL. Evaluation of MCF-7 cell cycles demonstrated that the extract arrested the cell cycle in the S phase and continued to the G2/M phase at the half of the IC50 value. The extract induced apoptotic of MCF-7 cell about 43.31% in which this activity was nearly the same with doxorubicin as a positive control (59.14%). However, solamargine was predicted as the most active anticancer compounds by a molecular docking study so that it was suggested to measure the level of this compound. Conclusion: It can be concluded that the fruit of S. nigrum L. ethanolic-70% extract demonstrated cytotoxic activity toward MCF-7 breast cancer cell and nontoxic on Vero normal cell. Solamargine was predicted as the most active anticancer compound. This extract had an opportunity to be developed as a potential anticancer agent to overcome breast cancer diseases.     

Propolis from the Stingless Bee Trigona incisa from East Kalimantan,Indonesia, Induces In Vitro Cytotoxicity and Apoptosis in Cancer Cell lines

Background: Previously, stingless bee (Trigona spp.) products from East Kalimantan, Indonesia, weresuccessfully screened for in vitro antiproliferative activity against human cancer derived cell lines. It wasestablished that propolis from T. incisa presented the highest in vitro cytotoxicity against the SW620 coloncancer cell line (6% cell survival in 20 μg/mL). Materials and Methods: Propolis from T. incisa was extractedwith methanol and further partitioned with n-hexane, ethyl acetate and methanol. The in vitro cytotoxicity ofthe extracts was assessed by the MTT assay against human colon (SW620), liver (Hep-G2), gastric (KATO-III),lung (Chago) and breast (BT474) cancer derived cell lines. The active fractions were further enriched by silicagel quick column, absorption and size exclusion chromatography. The purity of each fraction was checked bythin layer chromatography. Cytotoxicity in BT-474 cells induced by cardanol compared to doxorubicin wereevaluated by MTT assay, induction of cell cycle arrest and cell death by flow cytometric analysis of propidiumiodide and annexin-V stained cells. Results: A cardol isomer was found to be the major compound in one activefraction (F45) of T. incisa propolis, with a cytotoxicity against the SW620 (IC50 of 4.51 ± 0.76 μg/mL), KATO-III(IC50 of 6.06 ± 0.39 μg/mL), Hep-G2 (IC50 of 0.71 ± 0.22 μg/mL), Chago I (IC50 of 0.81 ± 0.18 μg/mL) and BT474(IC50 of 4.28 ± 0.14 μg/mL) cell lines. Early apoptosis (programmed cell death) of SW620 cells was induced bythe cardol containing F45 fraction at the IC50 and IC80 concentrations, respectively, within 2-6 h of incubation.In addition, the F45 fraction induced cell cycle arrest at the G1 subphase. Conclusions: Indonesian stingless bee(T. incisa) propolis had moderately potent in vitro anticancer activity on human cancer derived cell lines. Cardolor 5-pentadecyl resorcinol was identified as a major active compound and induced apoptosis in SW620 cells inan early period (≤ 6 h) and cell cycle arrest at the G1 subphase. Thus, cardol is a potential candidate for cancerchemotherapy.     

红花提取物不同组分的体外抑瘤实验研究

目的： 探究红花提取物抑瘤作用的有效组分。方法：选择人慢性粒细胞白血病K562细胞、人肝癌SMMC7721细胞、人宫颈癌HeLa细胞、人肺癌细胞H1299及A549共5株人常见肿瘤细胞株,用细胞计数试剂盒 (cell counting kit-8,CCK-8)方法对红花提取物及大孔树脂水-乙醇洗脱后的不同有效组分共6个供试品进行体外抑瘤作用评价,绘制浓度效应曲线,计算半数抑制浓度(IC50),比较各有效组分的抑瘤效果。结果：红花提取物各有效组分对肺癌细胞的抑制效果较好,IC50为16.24~189.86 μg/mL,其次为K562、SMMC7721及HeLa细胞。红花提取物脂溶性组分抑瘤作用较水溶性组分好,如红花提取物95%醇溶组分对5株肿瘤细胞均有明显的抑制作用,IC50为16.24~66.51 μg/mL。结论：红花提取物在体外对多种癌细胞有抑制作用,尤其是对肺癌细胞,其抑瘤作用有效物质可能是脂溶性组分。     

Cytotoxic and Antiproliferative Activity of Polyisoprenoids in Seventeen Mangroves Species Against WiDr Colon Cancer Cells

Background: Secondary metabolites from the group of isoprenoid compounds are widely distributed in mangroveplants. Polyisoprenoids (dolichol and polyprenol) are known to have benefits as anticancer agents. The present studywas conducted to determine the cytotoxic potential of polyisoprenoids in leaves from seventeen selected mangrovespecies against colon cancer (WiDr) cells. Methods: Cytotoxic activity was evaluated by MTT assay in vitro usingWiDr human colon cancer cells and 3T3 fibroblasts from Swiss albino mouse embryo tissue as controls. Mechanismsof action were approached by assessing apoptosis and the cell cycle using flow cytometry and fluorescence microscopywith annexin V-FITC, as well as expression of Bcl-2 and cyclin D1 by immunocytochemistry. Results: Polyisoprenoidsfrom N. fruticans leaves demonstrated the highest anticancer activity, with an IC50 of 180.2 μg/mL, as compared to397.7 μg/mL against 3T3 normal cells. Significant decrease in the expression of Bcl-2 and cyclin D1 was also noted,facilitating apoptosis and arrest of the cell cycle in the G0-G1 phase in WiDr cells. The present study showed for thefirst time that polyisoprenoids from N. fruticans exhibit concrete anticancer activity in vitro, decreasing cell proliferationand inducing apoptosis in colon cancer cells. Conclusions: Polyisoprenoids isolated from N. fruticans leaves may havepromise as a source of anticancer agents.     

Evaluation of In Vitro Cytotoxic Property Against Cholangiocarcinoma Cell Line and GC/MS Analysis from Leaf of Erythrophleum succirubrum Gagnep

Objective: Plants are valuable sources of new pharmaceuticals. Secondary metabolites of the genus Erythrophleum exhibit cytotoxicity and may have therapeutic value. The cytotoxic activity of ethanolic leaf extract of Erythrophleum succirubrum Gagnep. against a human cholangiocarcinoma cell line was assessed. Methods: Crude extract of E. succirubrum was prepared by ethanol extraction. The ethanolic leaf extract of E. succirubrum was evaluated for cytotoxicity against the human cholangiocarcinoma cell line KKU-M213 using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assays. The chemical composition of E. succirubrum leaf extract was analyzed using GC/MS. Result: The ethanolic leaf extract of E. succirubrum reduced the viability of KKU-M213 cells in a dose- and time-dependent manner. It showed high cytotoxicity, with IC50 values of 65.22 ± 1.18 µg/mL and 1.19 ± 1.38 µg/mL at exposure times of 24 and 96 h, respectively. GC/MS analysis of the ethanolic leaf extract of E. succirubrum identified 22 components. The main constituents identified were Cyclohexanone, 2-[2-nitro-1-(2-naphthyl)ethyl]-(14.79%) followed by allomycin (14.65%), mome inositol (14.30%), campesterol (11.80%) and ethyl linolenate (10.83%), respectively. Conclusion: Five major groups of compounds were found, with lipids dominating, followed by carbohydrates, benzenoids, phenylpropanoids, polyketides and organoheterocyclic compounds. Many of the bioactive components discovered in the ethanolic leaf extract of E. succirubrum might be responsible for its cytotoxic properties.     

Cytotoxic and Apoptotic Activity of Aglaforbesin Derivative Isolated from Aglaia loheri Merr. on HCT116 Human Colorectal Cancer Cells

Background: The genus Aglaia (Meliaceae) is an established source of many anticancer compounds. The study evaluated the leaf extracts of Aglaia loheri, a tree native to the Philippines, as potential source of anticancer compounds. Methods: Using bioassay-guided fractionation, A. loheri leaf extract was subjected to various chromatographic techniques and step-wise application of MTT assay on human colorectal carcinoma cells, HCT116, to determine the cytotoxic fractions. The most cytotoxic HPLC isolate was structurally identified using 1D and 2D NMR and its apoptotic effect was assessed by JC-1 staining, caspase 3/7 assay and TUNEL assay. Results: After stepwise chromatography fractionation, an HPLC isolate, structurally identified as aglaforbesin derivative (AFD), demonstrated potent cytotoxicity against HCT116. AFD exhibited strong toxicity (IC50 = 1.13 ±0.07 µg/mL) and high selectivity on HCT116 than normal human kidney cells (HK-2). AFD-induced toxicity to HCT116 is possibly through the stimulation of the apoptotic signaling pathway via caspase 3/7 activation and DNA fragmentation independent of mitochondrial membrane depolarization. Conclusion: AFD exhibited selective cytotoxicity and apoptotic activity to HCT116 and could be further developed as anticancer drug lead.     

Pregnane Steroids from the Leaves of Melia Azedarach and Apoptotic Activity against T47D Cells

Objective: Nature has provided us with many pharmaceutical resources so far. Breast cancer shows an increasing trend in the world for the last decade and becomes one of five leading causes of death. Among the plants, Melia azedarach L. has been used widely in traditional medicine for many ailments including breast cancer. Following our previous findings that the ethyl acetate fraction was the most active cytotoxic fraction against T47D cells, we aimed to isolate the cytotoxic compounds and further elucidate their apoptotic mechanisms. Methods: The compounds were isolated through a series of chromatography with cytotoxicity evaluations. Identification of the isolated compounds was achieved by intensive spectroscopic analysis such as NMR, MS, and IR spectra. Cytotoxicity was evaluated by MTT method using doxorubicin as a reference compound. The expression of apoptosis-related factors was quantified by flow cytometry and immunocytochemistry. Results: Two isomers of pregnane steroids with molecular weight 330.2087 (C21H30O3) were isolated from the EtOAc extract. Spectroscopic analysis revealed the structures as 17-ethylene-3,4-dihydroxy-14-methyl-18-norandrostene-16-one (1) and 17-ethylene-3,4-dihydroxy-5-pregnene-16-one (2), respectively. These compounds showed moderate cytotoxicity (IC50 172.9 and 62.2 µg/mL, respectively) comparable to doxorubicin (IC50 3.08 µg/mL). The execution of apoptosis may be related to the increase of the ratio of BAX/bcl-2 of the cells.  Conclusion: The EtOAc fraction of Melia azedarach L. leaves and the isolated 5-pregnene-16-one steroids are promising reagents for breast cancer treatment by introducing apoptosis to tumor cells. However, further researches are required to highlight its safety and usage in vivo.     

Evaluation of novel ammine/amine platinum (IV) dicarboxylates in L1210 murine leukaemia cells sensitive and resistant to cisplatin, tetraplatin or carboplatin.

Seventeen alkylamine ammine dicarboxylatodichloroplatinum(IV) complexes of general structure c,t,c-[PtCl2(OCOR1)2NH3(RNH2)], where R = aliphatic or alicyclic and R1 = aliphatic or aromatic, have been evaluated against L1210 cell lines with acquired resistance to cisplatin (10-fold), tetraplatin (34-fold) or carboplatin (14-fold) using an in vitro growth-delay assay. All of these compounds overcame cisplatin, tetraplatin and carboplatin resistance. Potency increased as the number of carbon atoms in the axial aliphatic ligands (R1) increased, for example comparing JM216 (R = cyclohexyl, R1 = CH3, IC50 = 1.2 microM) with JM274 (R = cyclohexyl, R1 = n-C4H9, IC50 = 0.05 microM) against the parent sensitive line (L1210/S). The most active compounds were those possessing aromatic ligands at R1, regardless of whether R = aliphatic or alicyclic, for example JM244 (R = n-C3H7, R1 = C6H5, IC50 = 0.028 microM) and JM2644 (R = c-C6H11, R1 = C6H5, IC50 = 0.031 microM) against L1210/S. For an alicyclic alkylamine series in which R is varied from c-C3H7 to C-C7H13, with R1 = n-C3H7 for each compound, cytotoxic potency was maximised at c-C6H11 (JM221, IC50 = 0.06 microM against L1210/S). Preliminary biochemical studies, at equitoxic doses, comparing JM221 (0.1 microM) with cisplatin (0.6 microM) identified five times more platinum associated with JM221 treated cells and 1.5 times more platinum bound to the DNA of JM221-treated cells. The lipophilic properties of some of these platinum(IV) dicarboxylates may contribute to both the potency and circumvention of resistance by these compounds.     

Anti Proliferative and Apoptotic Effect of Soluble Ethyl Acetate Partition from Ethanol Extract of Chromolaena Odorata Linn Leaves Against Hela Cervical Cancer Cell line

Background: Cervical cancer is the leading cause of cancer death in women. Chemotherapy is one of the treatment modalities with many side effects. This study aimed to evaluate the anticancer activity of soluble ethyl acetate partition of Chromolaena odorata (C. odorata) leaves on HeLa cells of cervical cancer. Material and methods: The cytotoxicity activity of the soluble ethyl acetate extract of the C. odorata leaves was analyzed by MTT colorimetry assay. The apoptosis activity was determined by double staining and flow cytometry techniques. Doubling time assay was used to observed HeLa cells proliferation. Results: The IC50 of soluble ethyl acetate partition of this plant was 82.41± 6.73 µg/ml against HeLa cells. The apoptosis activity showed that HeLa cells underwent morphological changes in dose-dependent manner while the highest number of dead cells was observed after treatment with 500 µg/ml of the partition. Flow cytometry analysis showed that treatment with IC50 and 2x IC50 resulted in death of more than 97% cells (p-value <0.05 in both comparisons). Proliferation of HeLa cells was also inhibited following treatment with ½ IC50, IC50, and 2xIC50 in the first 24 hours (p-value <0.05 in all comparison). Conclusion: The findings of this study suggested that the soluble ethyl acetate partition from ethanol extract of C. odorata leaves had cytotoxic and antiproliferative properties against HeLa cells.     

In vitro cancer chemotherapeutic activity of 1,10-phenanthroline (phen), [Ag2(phen)3(mal)]x2H2O, [Cu(phen)2(mal)]x2H2O and [Mn(phen)2(mal)]x2H2O (malH2=malonic acid) using human cancer cells

The chemotherapeutic potential of 1,10-phenanthroline (phen), and three of its transition metal complexes, namely [Cu(phen)(2)(mal)]x2H(2)O, [Mn(phen)(2)(mal)]x2H(2)O and [Ag(2)(phen)(3)(mal)]x2H(2)O (malH(2)=malonic acid) was determined using two human carcinoma cell lines (A-498 and Hep-G2). Phen and the three metal-phen complexes induced a concentration-dependent cytotoxic effect, with metal complexes demonstrating the greatest cytotoxic response. In comparative studies, IC(50) values show cytotoxicity of between 3 and 18 times greater than that observed for the metal-based anti-cancer agent, cisplatin. All of the phen-based complexes inhibited DNA synthesis which did not appear to be mediated through intercalation. Also, the potential cancer chemotherapeutic application of these compounds was seen to be enhanced by results obtained from Ames tests, which showed all of the test agents and their phase I metabolites were non-mutagenic. Taken together, these results suggest that phen and the three metal-phen complexes may have a therapeutic role to play in the successful treatment and management of cancer.     

In vitro Evaluation of Cytotoxic Activities of Essential Oil from Moringa oleifera Seeds on HeLa,HepG2, MCF-7, CACO-2 and L929 Cell Lines

Moringa oleifera Lam. (Moringaceae) is widely consumed in tropical and subtropical regions for their valuablenutritional and medicinal characteristics. Recently, extensive research has been conducted on leaf extracts of M.oleifera to evaluate their potential cytotoxic effects. However, with the exception of antimicrobial and antioxidantactivities, little information is present on the cytotoxic activity of the essential oil obtained from M. oleifera seeds.Therefore, the present investigation was designed to investigate the potential cytotoxic activity of seed essentialoil obtained from M. oleifera on HeLa, HepG2, MCF-7, CACO-2 and L929 cell lines. The different cell lineswere subjected to increasing oil concentrations ranging from 0.15 to 1 mg/mL for 24h, and the cytotoxicity wasassessed using MTT assay. All treated cell lines showed a significant reduction in cell viability in response to theincreasing oil concentration. Moreover, the reduction depended on the cell line as well as the oil concentrationapplied. Additionally, HeLa cells were the most affected cells followed by HepG2, MCF-7, L929 and CACO-2,where the percentages of cell toxicity recorded were 76.1, 65.1, 59.5, 57.0 and 49.7%, respectively. Furthermore,the IC50 values obtained for MCF-7, HeLa and HepG2 cells were 226.1, 422.8 and 751.9 μg/mL, respectively.Conclusively, the present investigation provides preliminary results which suggest that seed essential oil fromM. oleifera has potent cytotoxic activities against cancer cell lines.     

In Vitro Cytotoxic Activity of Clinacanthus nutans Leaf Extracts Against HeLa Cells

Objective: This study was conducted to investigate the antiproliferative activity of extracts of Clinacanthus nutansleaves against human cervical cancer (HeLa) cells. Methods: C. nutans leaves were subjected to extraction using 80%methanol or water. The methanol extract was further extracted to obtain hexane, dichloromethane (DCM), and aqueousfractions. The antiproliferative activity of the extracts against HeLa cells was determined. The most cytotoxic extractwas furthered analyzed by apoptosis and cell cycle assays, and the phytochemical constituents were screened by gaschromatography-mass spectrometry (GC-MS). Results: All of the extracts were antiproliferative against HeLa cells, andthe DCM fraction had the lowest IC50 value of 70 μg/mL at 48 h. Microscopic studies showed that HeLa cells exposedto the DCM fraction exhibited marked morphological features of apoptosis. The flow cytometry study also confirmedthat the DCM fraction induced apoptosis in HeLa cells, with cell cycle arrest at the S phase. GC-MS analysis revealedthe presence of at least 28 compounds in the DCM fraction, most of which were fatty acids. Conclusion: The DCMfraction obtained using the extraction method described herein had a lower IC50 value than those reported in previousstudies that characterized the anticancer activity of C. nutans against HeLa cells.     

Screening for in vitro Cytotoxic Activity of Seaweed,Sargassum sp. Against Hep-2 and MCF-7 Cancer Cell Lines

Discovery of anticancer drugs that kill or disable tumor cells in the presence of normal cells without undue toxicity is a potential challenge for therapeutic care. Several papers in the literature have emphasized the potential implications of marine products such as seaweeds which exhibit antitumor activity. Study attempts to screen the antitumor effect of Sargassum sp, against chosen cell lines such as MCF-7 (Breast cancer) and Hep-2 (Liver Cancer). Ethanol extract of Sargassum sp. was concentrated using a Soxhlet apparatus and dissolved in DMSO.In vitro cytotoxic activity of Sargassum sp at various concentrations (100 μg/ml-300 μg/ml) screened for antitumor effect against the chosen cell lines using MTT assay (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide, a yellow tetrazole). The study documented that the percentage of cell viability has been reduced with increased concentration, as evidenced by cell death. Sargassum sp extract shows potential cytotoxic activity (P≤0.05) with IC50 of 200 μg/ml and 250 μg/ml against Hep-2 and MCF-7 cell lines respectively. The ethanol fraction of Sargassum sp induced cell shrinkage, cell membrane blebbing and formation of apoptotic bodies with evidence of bioactive components as profound influencing factors for anti-tumor effects. Further research need to be explored for the successful application of Sargassum sp as a potent therapeutic tool against cancer.     

Cytotoxicity, DNA damage, and cell cycle perturbations induced by two representative gold(III) complexes in human leukemic cells with different cisplatin sensitivity.

The gold(III) complexes [Au(phen)Cl2]Cl and [Au(dien)Cl]Cl2 were recently shown to exert important cytotoxic effects in vitro on human tumor cell lines. To elucidate the biochemical mechanisms leading to cell death, the effects produced by these gold(III) complexes on the leukemic CCRF-CEM cell line--either sensitive (CCRF-CEM) or resistant to cisplatin (CCRF-CEM/CDDP)--were analyzed in detail by various techniques. For comparison purposes the effects produced by equitoxic concentrations of cisplatin were also analyzed. First, the dependence of the IC50 values of either complex on the incubation time was investigated. Cytotoxicity experiments confirmed that both gold(III) compounds retain their efficacy against the cisplatin-resistant line: only minimal cross-resistance with cisplatin was detected. Notably, [Au(phen)Cl2]Cl is more cytotoxic than [Au(dien)Cl]Cl2, with IC50 values of 7.4 and 6.0 M at 24 and 72 h, respectively, on the resistant line. Results of the COMET assay point out that both gold(III) complexes directly damage nuclear DNA. Remarkably, DNA damage inferred by either gold(III) complex in the two cell lines is larger than that produced by equitoxic cisplatin concentrations. Finally, the effects that either gold(III) complex produces on the cell cycle were investigated by flow cytometry. It was found that both complexes cause only moderate and transient cell cycle perturbations. Larger cell cycle perturbations are induced by equitoxic concentrations of cisplatin. The implications of the present results for the mechanism of action of cytotoxic gold(III) complexes are discussed.     

Structure-activity relationships defining the cytotoxicity of catechol analogues against human malignant melanoma

The cytotoxic activities of three new synthetic catechol analogues, beta-[(p-hydroxyphenyl)amino]alanine (Compound 1), N delta-(p-hydroxyphenyl)ornithine (Compound 2), and N delta-(m-hydroxyphenyl)ornithine (Compound 3), were determined against 10 human melanoma and 5 nonmelanoma cell lines. Activities of L-DOPA and 3,4-dihydroxybenzylamine were also measured. Dose-response curves were obtained and concentrations in micrograms/ml required to give 90% inhibition of colony formation (IC90) were calculated. Using a cutoff IC90 of less than 2.5 as a definition of activity. Compound 2 was active in 6 of 10 melanoma and 0 of 5 nonmelanoma cell lines while both Compound 1 and L-DOPA methyl ester were active in 1 of 10 melanomas and 0 of 5 nonmelanomas. Compound 3 was inactive in all cell lines and all IC90 values exceeded 100. 3,4-Dihydroxybenzylamine was active in 3 of 8 melanomas and 1 of 5 nonmelanomas. Regression analysis of IC90 values for Compound 2 and tyrosinase levels in the 15 cell lines yielded a correlation coefficient of 0.93 (P less than 0.001). By contrast, a similar analysis for 3,4-dihydroxybenzylamine gave a correlation coefficient of 0.17 (P greater than 0.05). Spectrophotometric data indicated that Compounds 1 and 2 were oxidized by tyrosinase to quinones. Cytotoxic activity was blocked by the tyrosinase inhibitor phenylthiocarbamide. Since the rates of activation of Compounds 1 and 2 were identical, the higher activity of Compound 2 was probably due to its higher lipophilicity and greater intracellular accumulation. Compounds 1 and 2 exhibited greater potency and selectivity against malignant melanoma than did the natural product L-DOPA methyl ester.     

Anticancer Activity of Combretum fragrans F. Hoffm on Glioblastoma and Prostate Cancer Cell Lines

Background: Cancer incidence has been growing in an alarming rate worldwide and new therapeutics are needed, particularly for intractable and chemoresistant cases. We evaluated the cytotoxic effects of Combretum fragrans F. Hoffm (Combretaceae) on glioblastoma (U87MG and C6) and prostate (PC-3) cancer cell lines. Methods: The cytotoxic effect of the methanolic extract of the stem bark of Combretum fragrans was assessed using XTT (2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide) test. Expressions of Akt and ERK1/2 were determined using Western blot technique, while Caspase-3/7 kits were used to evaluate caspase-3/7 activity. Results: C. fragrans extract inhibited the proliferation of U87 (IC50 = 20.13 µg/mL), C6 (IC50 = 12.17 µg/mL), and PC-3 (IC50 = 11.50 µg/mL) cells. Treatment with the extract resulted in lower levels (p < 0.001) of phospho-ERK1/2 and phospho-Akt in U87 cells, and instead, higher levels of phospho-ERK1/2 (p < 0.001) in C6 and PC-3 cells. An increase in caspase-3/7 activity was observed, mainly after 24 hours of treatment, indicating the activation of apoptotic processes. Conclusion: Altogether, these results suggest that C. fragrans have potent anticancer properties. This plant should be further investigated for developing new anticancer drugs.