scholarly journals Cytotoxic Activity of Familact: A Probiotic Supplement

2018 ◽  
Vol 12 (4) ◽  
pp. 41-45
Author(s):  
Zahra Yahyavi ◽  
◽  
Mohammad Reza Fazeli ◽  
Mani Mirfeizi ◽  
Shima Aliebrahimi ◽  
...  

Background: Lactobacillus and Bifidobacterium species are among the probiotics discussed due to their anti-cancer effects in the treatment of colorectal and breast cancers in recent studies. The aim of this study was to investigate the anticancer effect of Familact, a commercial probiotic capsule containing seven bacterial strains (L. casei, L. acidophilus, L. rhamnosus, L. bulgaricus, B. breve, B. longum and Streptococcus thermophilus). Methods: Various cancer cell lines including Caco-2, HT-29, T47D and normal cell line L929 were treated with different concentrations of Familact. Using MTT assay, the cytotoxicity effect was investigated for each cell line and then flow cytometry analysis of apoptosis was evaluated. Results: Familact demonstrated inhibitory effects on the proliferation of all tested cancer cell lines in a dose-dependent manner. Although Familact augmented apoptotic cell death in HT-29 human cancer cells, it was less effective in the case of Caco-2 and T47D cells. Moreover, exposure to Familact showed moderate cytotoxicity towards L929 mouse fibroblast cells. Conclusion: Familact could be considered as a complementary therapy in the treatment of cancers.

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Zahra Tayarani-Najaran ◽  
Seyed Ahmad Emami ◽  
Javad Asili ◽  
Alireza Mirzaei ◽  
Seyed Hadi Mousavi

TheScutellariaspecies (Lamiaceae) is used as a source of flavonoids to treat a variety of diseases in traditional medicine. In spite of many reports about the cytotoxic and antitumor effects of some species of this genus, anticancer researches on one of the Iranian speciesS. litwinowiihave not yet been conducted.The cytotoxic properties of total methanol extract ofS. litwinowiiand its fractions were investigated on different cancer cell lines including AGS, HeLa, MCF-7, PC12 and NIH 3T3. Meanwhile, the role of apoptosis in this toxicity was explored. The cells were cultured in DMEM medium and incubated with different concentrations of herb plant extracts. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using propidium iodide staining of DNA fragmentation by flow cytometry (sub-G1 peak).Scutellaria litwinowiiinhibited the growth of malignant cells in a dose-dependent manner. Among solvent fractions ofS. litwinowii, the methylene chloride fraction was found to be more toxic compared to other fractions. The IC50values of this fraction against AGS, HeLa, MCF-7 and PC12 cell lines after 24 h were determined, 121.2 ± 3.1, 40.9 ± 2.5, 115.9 ± 3.5 and 64.5 ± 3.4μg/ml, respectively.Scutellaria litwinowiiinduced a sub-G1 peak in the flow cytometry histogram of treated cells compared to control cells indicating that apoptotic cell death is involved inS. litwinowiitoxicity.Scutellaria litwinowiiexerts cytotoxic and proapototic effects in a variety of malignant cell lines and could be considered as a potential chemotherapeutic agent in cancer treatment.


2020 ◽  
Vol 32 (5) ◽  
pp. 1197-1202
Author(s):  
Consolacion Y. Ragasa ◽  
Glenn G. Oyong ◽  
Maria Carmen S. Tan ◽  
Mariquit M. De Los Reyes ◽  
Maria Ellenita G. De Castro

Ergosterol peroxide (1) and ergosterol (2) were commonly isolated as the major compounds of Philippine mushrooms. Sterols 1 and 2 from the dichloromethane extract of Geastrum triplex and Termitomyces clypeatus, respectively, were evaluated for their cytotoxic activities against four human cancer cell lines, viz., breast cancer (MCF-7), colon cancer (HT-29), leukemia (THP-1), and small lung cell carcinoma (H69PR), and a human normal cell line, human dermal fibroblast-neonatal (HDFn), using the PrestoBlue® cell viability assay. Compounds 1 and 2 exhibited the strongest activities against HT-29 with IC50 values of 1.79 and 2.98 μg/mL, respectively, while Zeocin gave an IC50 of 4.89 μg/mL. These compounds also exhibited strong antiproliferative effects against MCF-7 with IC50 values of 4.13 for 1 and 4.20 μg/mL for compound 2, comparable to Zeocin with IC50 = 3.68 μg/mL. Only moderate cytotoxicity resulted when compounds 1 and 2 were tested against H69PR with IC50 values of 7.78 and 6.83 μg/mL, respectively, while Zeocin exhibited an IC50 of 9.81 μg/mL. Furthermore, compounds 1 and 2 showed no effects against THP-1 (IC50 > 100 μg/mL), while Zeocin showed an IC50 of 4.73 μg/mL. Although compounds 1 and 2 have been reported to exhibit different bioactivities in previous studies, the cancer cell lines tested and/or the polarities of the solvents for extraction varied. Therefore, comparisons of the cytotoxic activities of compounds 1 and 2 with earlier studies could not be made extensively.


Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3625 ◽  
Author(s):  
Antipova ◽  
Samoylenkova ◽  
Savchenko ◽  
Zavyalova ◽  
Revishchin ◽  
...  

Oligonucleotides with an antiproliferative activity for human cancer cells have attracted attention over the past decades; many of them have a G-quadruplex structure (GQ), and a cryptic target. In particular, DNA oligonucleotide HD1, a minimal GQ, could inhibit proliferation of some cancer cell lines. The HD1 is a 15-nucleotide DNA oligonucleotide that folds into a minimal chair-like monomolecular antiparallel GQ structure. In this study, for eight human cancer cell lines, we have analyzed the antiproliferative activities of minimal bimodular DNA oligonucleotide, biHD1, which has two HD1 modules covalently linked via single T-nucleotide residue. Oligonucleotide biHD1 exhibits a dose-dependent antiproliferative activity for lung cancer cell line RL-67 and cell line of central nervous system cancer U87 by MTT-test and Ki-67 immunoassay. The study of derivatives of biHD1 for the RL-67 and U87 cell lines revealed a structure-activity correlation of GQ folding and antiproliferative activity. Therefore, a covalent joining of two putative GQ modules within biHD1 molecule provides the antiproliferative activity of initial HD1, opening a possibility to design further GQ multimodular nanoconstructs with antiproliferative activity—either as themselves or as carriers.


Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3755 ◽  
Author(s):  
James Knockleby ◽  
Bruno Pradines ◽  
Mathieu Gendrot ◽  
Joel Mosnier ◽  
Thanh Tam Nguyen ◽  
...  

Natural products remain a viable source of novel therapeutics, and as detection and extraction techniques improve, we can identify more molecules from a broader set of plant tissues. The aim of this study was an investigation of the cytotoxic and anti-plasmodial activities of the methanol extract from Stephania dielsiana Y.C. Wu leaves and its isolated compounds. Our study led to the isolation of seven alkaloids, among which oxostephanine (1) is the most active against several cancer cell lines including HeLa, MDA-MB231, MDA-MB-468, MCF-7, and non-cancer cell lines, such as 184B5 and MCF10A, with IC50 values ranging from 1.66 to 4.35 μM. Morever, oxostephanine (1) is on average two-fold more active against cancer cells than stephanine (3), having a similar chemical structure. Cells treated with oxostephanine (1) are arrested at G2/M cell cycle, followed by the formation of aneuploidy and apoptotic cell death. The G2/M arrest appears to be due, at least in part, to the inactivation of Aurora kinases, which is implicated in the onset and progression of many forms of human cancer. An in-silico molecular modeling study suggests that oxostephanine (1) binds to the ATP binding pocket of Aurora kinases to inactivate their activities. Unlike oxostephanine (1), thailandine (2) is highly effective against only the triple-negative MDA-MB-468 breast cancer cells. However, it showed excellent selectivity against the cancer cell line when compared to its effects on non-cancer cells. Furthermore, thailandine (2) showed excellent anti-plasmodial activity against both chloroquine-susceptible 3D7 and chloroquine-resistant W2 Plasmodium falciparum strains. The structure–activity relationship of isolated compound was also discussed in this study. The results of this study support the traditional use of Stephania dielsiana Y.C. Wu and the lead molecules identified can be further optimized for the development of highly effective and safe anti-cancer and anti-plasmodial drugs.


Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 677 ◽  
Author(s):  
Hong-Jhih Lin ◽  
Jinn-Hsuan Ho ◽  
Li-Chen Tsai ◽  
Fang-Yu Yang ◽  
Ling-Ling Yang ◽  
...  

The objective of this study was to synthesize the 9-/13-position substituted berberine derivatives and evaluate their cytotoxic and photocytotoxic effects against three human cancer cell lines. Among all the synthesized compounds, 9-O-dodecyl- (5e), 13-dodecyl- (6e), and 13-O-dodecyl-berberine (7e) exhibited stronger growth inhibition against three human cancer cell lines, (HepG2, HT-29 and BFTC905), in comparison with structurally related berberine (1). These three compounds also showed the photocytotoxicity in human cancer cells in a concentration-dependent and light dose-dependent manner. Through flow cytometry analysis, we found out a lipophilic group at the 9-/13-position of berberine may have facilitated its penetration into test cells and hence enhanced its photocytotoxicity on the human liver cancer cell HepG2. Further, in cell cycle analysis, 5e, 6e, and 7e induced HepG2 cells to arrest at the S phase and caused apoptosis upon irradiation. In addition, photodynamic treatment of berberine derivatives 5e, 6e, and 7e again showed a significant photocytotoxic effects on HepG2 cells, induced remarkable cell apoptosis, greatly increased intracellular ROS level, and the loss of mitochondrial membrane potential. These results over and again confirmed that berberine derivatives 5e, 6e, and 7e greatly enhanced photocytotoxicity. Taken together, the test data led us to conclude that berberine derivatives with a dodecyl group at the 9-/13-position could be great candidates for the anti-liver cancer medicines developments.


2011 ◽  
Vol 66 (3-4) ◽  
pp. 143-148 ◽  
Author(s):  
Hossam M. Abdallah ◽  
Shahira M. Ezzat

The aerial parts of Pituranthos tortuosus (Desf.) Benth and Hook (Apiaceae), growing wild in Egypt, yielded 0.8%, 0.6%, and 1.5% (v/w) of essential oil when prepared by hydrodistillation (HD), simultaneous hydrodistillation-solvent (n-pentane) extraction (Lickens- Nickerson, DE), and conventional volatile solvent extraction (preparation of the “absolute”, SE), respectively. GC-MS analysis showed that the major components in the HD sample were β-myrcene (18.81%), sabinene (18.49%), trans-iso-elemicin (12.90%), and terpinen- 4-ol (8.09%); those predominent in the DE sample were terpinen-4-ol (29.65%), sabinene (7.38%), γ-terpinene (7.27%), and β-myrcene (5.53%); while the prominent ones in the SE sample were terpinen-4-ol (15.40%), dill apiol (7.90%), and allo-ocimene (4E,6Z) (6.00%). The oil prepared in each case was tested for its cytotoxic activity on three human cancer cell lines, i.e. liver cancer cell line (HEPG2), colon cancer cell line (HCT116), and breast cancer cell line (MCF7). The DE sample showed the most potent activity against the three human cancer cell lines (with IC50 values of 1.67, 1.34, and 3.38 μg/ml against the liver, colon, and breast cancer cell lines, respectively). Terpinen-4-ol, sabinene, γ-terpinene, and β-myrcene were isolated from the DE sample and subjected to a similar evaluation of cytotoxic potency; signifi cant activity was observed


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3806-3806
Author(s):  
Claudia Scholl ◽  
Stefan Frohling ◽  
Ian F. Dunn ◽  
David A. Barbie ◽  
Anna C. Schinzel ◽  
...  

Abstract Activating RAS mutations are among the most common pathogenetic events in a broad spectrum of hematologic malignancies and epithelial tumors. However, oncogenic RAS has thus far not proven to be a tractable target for therapeutic intervention. An alternative to direct targeting of known oncogenes is to perform “synthetic lethality” screens to identify genes that are selectively required for cell viability in the context of specific cancer-causing mutations. Using this approach, we have discovered a synthetic lethal interaction between mutant KRAS, the most frequently mutated oncogene in human cancer, and inactivation of the gene encoding the STK33 serine/threonine protein kinase. To identify genes that are essential for cell viability in the context of mutant KRAS, we performed high-throughput loss-of-function RNA interference (RNAi) screens in eight human cancer cell lines (mutant KRAS, n=4; wildtype KRAS, n=4), representing seven different tumor types (acute myeloid leukemia, multiple myeloma, colon cancer, breast cancer, ovarian cancer, prostate cancer, glioblastoma), as well as normal human fibroblasts and mammary epithelial cells. We screened each cell line with a subset of the short hairpin RNA (shRNA) library developed by the RNAi Consortium (http://www.broad.mit.edu/genome_bio/trc/rnai.html) that consists of 5,024 individual shRNA constructs targeting 1,011 human genes, including the majority of known and putative protein kinase and phosphatase genes and a selection of known cancer-related genes. In these cell lines, suppression of STK33 preferentially inhibited the viability and proliferation of cells that were dependent on mutant KRAS. The differential requirement for STK33 based on oncogenic KRAS dependency was confirmed in 16 additional cell lines using in vitro transformation assays and human tumor xenograft models. Biochemical analyses support the hypothesis that STK33 promotes cell growth and survival in a kinase activity-dependent manner by regulating the activity of S6K1 as well as BAD-induced apoptosis selectively in mutant KRAS-dependent cells. Notably, molecular genetic characterization of cancer cell lines and analysis of patient-derived genomic data sets indicate that STK33 is not frequently mutated or overexpressed in human tumors. These observations identify STK33 as a potential target for the treatment of mutant KRAS-driven cancers that may have a broad therapeutic index in normal versus malignant cells, and illustrate the potential of RNAi for discovering critical functional dependencies created by oncogenic mutations that cannot be identified using other genomic technologies.


2019 ◽  
Vol 9 (4-s) ◽  
pp. 1195-1202
Author(s):  
Nirmala Devi ◽  
Ajay Kumar Gupta ◽  
Sunil Kumar Prajapati

Aims: Apocynaceae family is the 5th largest medicinal plant family rich in potent secondary metabolites such as Alkaloids, Cardiac glycosides,Terpenoids, irridoid/secoirridoids, flavonoids and Phenolic contents. The present study was aimed to evaluate and compare in-vitroantiproliferative activity of three plants of this family.Methods: Aerial parts of Carissa carandas Linn. (C), Nerium indicum Mill. (N) and Wrightia tinctoria RBr. (W), were collected and dried. Thepowdered drugs were extracted in Ethanol (1), 60% Ethanol (2) and Water (3). Estimation of Phytoconstituents performed using standardmethods. In-vitro cytotoxic activity performed using Sulphorhodamine B (SRB) assay in HepG2, HT29 and SKOV3 human cancer cell lines takingAdriamycin (ADR) as standard. For extracts, GI50 value ≤ 20μg/ml was considered to demonstrate activity.Results: For HepG2 cell line graphs and photomicrographs showed GI50 value as ADR=39.79, C1=2.5, N2=66.3, N3<10 and C2=C3= N1=W1-3>80. Also TGI for C1>80. The extracts, C1, C2, N1, N2, and N3 were found to possess activity against HepG2.These extracts were screened onHT 29 and SKOV3cell lines. The GI50 value observed was<10 for C1, N2, N3 and ADR in HT 29 and <10 for N3 and ADR in SK OV3 cell lines.Thus it was found that aqueous extract of Nerium indicum (N3) and Ethanolic extract of Carissa carandas (C1) were most cytotoxic extractsagainst all three cell lines.Conclusions: our study establishes that Apocynaceae family plants could be an important anticancer lead and could serve as Botanical drug forneoplasia.Keywords: Apocynaceae, SRB Assay, Phytoconstituents, Anticancer drug screening models, Hep G2, HT 29, SK-OV3, HCC.


Synlett ◽  
2021 ◽  
Author(s):  
Anh Tuan Tran ◽  
Chien Van Tran ◽  
Hai Van Le ◽  
Loc Van Tran ◽  
Thao Thi Phuong Tran ◽  
...  

AbstractSynthesis of tubulysin analogues, containing an N-methyl substituent on tubuvaline-amide together with the replacement of either the hydrophobic N-terminal N-methyl pipecolic acid (Mep) or at both N- and C- terminal peptides with available heteroaromatic acids and an unsaturated tubuphenylalanine moiety, respectively, were described. The in vitro cytotoxic activity by SRB assay on five cancer cell lines for sixteen tubulysins was evaluated. Among them, five analogues exhibited strong cytotoxic activities against five human cancer cell lines, including human breast carcinoma (MCF7), human colorectal adenocarcinoma (HT-29), HL-60, SW-480, human lung adenocarcinoma (A459). Interestingly, one analogue showed the strongest cytotoxicity on all five tested cell lines even much higher toxicity than the reference compound ellipticine.


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