Apoptotic Potential of Artemsia sieberia Besser (Asteraceae) Fraction against Human Cancer Cell Lines

Purpose: To investigate the anti-proliferative and apoptotic activity of crude and dichloromethane fraction of A. sieberi against seven cancer cell lines (Colo20, HCT116, DLD, MCF7, Jurkat, HepG2 and L929).Methods: A. sieberi was extracted with methanol and further purification was carried out using liquidliquid extraction with hexane, dichloromethane and ethyl acetate. Each extract was assayed for cytotoxic potential against cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide (MTT) assay. The morphology of the HepG2 cell nucleus was investigated by Hoechst 33342, DNA-binding dye. A Tali™ image-based cytometer was used to assess cell viability, death and apoptosis using annexin-v /pi (propidium iodide). A chromatographic fingerprint was constructed using high performance liquid chromatography (HPLC).Results: The most effective anticancer activity of the unrefined methanol extract was against HepG2 cell lines (LC50 = 161.5 μg/mL). The hexane and ethyl acetate fractions showed no antiproliferative activity. The dichloromethane fraction displayed higher cytotoxic activity (LC50 = 61.75 μg/mL) and also repressed the migration of the cells. About 50 % of HepG2 cells were apoptotic when treated for 24 h with the dichloromethane fraction at the concentration of 120 μg/mLConclusion: A. sieberi possesses apoptotic activity and inhibited the migration of the HepG2 cell lines.Keywords: Artemsia Sieberia, Apoptosiss, Cytotoxicity, Hoescht staining, HepG2 cell line

ANTICANCER POTENTIAL OF PLANT EXTRACTS FROM RIYADH (SAUDI ARABIA) ON MDA-MB-231 BREAST CANCER CELLS

Background: Medicinal plants have been used in traditional medicine for the treatment of numerous diseases worldwide. There is a dire need for new anticancer agents and plants used in traditional medicine are a particularly useful source. Materials and methods: In this study, extracts of five different plants that grow in the desert of Saudi Arabia were evaluated to assess their cytotoxicity against the MDA-MB-231 breast cancer cell line. Soxhlet extraction was carried out on the leaves and stems using different solvents. The cytotoxicity of these extracts against MDA-MB-231 breast cancer cells was assessed using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. The apoptotic cellular morphological changes were observed using inverted and fluorescence microscopes. Results: Our results showed that two of the five different medicinal plants (Rumex vesicarius and Malva parviflora) exhibited strong anticancer activity against the breast cancer cells. Specifically, 2 of the 40 extracts (from the five studied plants) showed promising activity. The chloroform extract of the stem of R. vesicarius (RSV CHCL3) exhibited moderate anticancer activity with a half-maximal inhibitory concentration (IC50) of 230 µg/mL while that of the hexane extract of M. parviflora stems (MPS Hex) was 248 µg/mL. Loss of cell integrity, shrinkage of the cytoplasm, and cell detachment were observed in the extract-treated MDA-MB-231 cells. Conclusion: R. vesicarius and M. parviflora chloroform and n-hexane stem extracts showed significant cytotoxicity against MDA-MB-231 human breast carcinoma cells

Psiadia punctulata (DC.) Vatke induces cell apoptosis in highly metastatic MDA-MB-231 cells

Purpose: This study assessed the in vitro cell migration inhibitory and cell apoptotic effects of P. punctulata stem (PPS (and leaf hexane) PPL (extracts on breast cancer cell lines (MDA-MB-231 andMCF-7 cells).Methods: Cytotoxicity was quantified using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LD) release test after 48 h exposure of MDA-MB-231 cells to 0 – 200 μg/mL of PPS and PPL hexane extract. Cell apoptosis was determined using Muse™ cell cytometry, while the phytoconstituents of PPS and PPL hexane extracts were identified by gas chromatography–mass spectrometry.Results: The half-maximal inhibitory concentration (IC50) for PPS and PPL hexane extracts against MDA-MB-231 cells was 44.33 and 52.16 μg/mL, respectively. T, whereas the IC50 of PPS and PPL hexane extracts was 102.22 and 59.53 μg/mL against MCF-7 cells, sequentially. Treatment with 100 and 200 μg/mL of PPS and PPL hexane extract increased late apoptosis in MDA-MB-231 cells to 16.005 ± 1.155 and 52.58 ± 3.02 %, respectively, for PPS hexane extract and 77.34 ± 0 % and 95.21 ± 1.61 %, respectively, for PPL hexane extract, when compared to control cells (3.81% ± 0.79%). PPL hexane extract decreased cell migration and filled ~15.5 % of the wound gap on MDA-MB-231 cells after 24 h, while PPS hexane extract decreased cell migration by ~35 and ~42.5 % at 24 and 48 h, respectively. PPS and PPL hexane extracts contained several phytocompounds. Stem and leaf extracts of P. punctulata showed significant (p < 0.05) cell apoptotic and migration inhibition activities.Conclusion: The extracts P. punctulata exhibit potent cytotoxic activity against the tested breast cancer cells. Further research is required to assess the acute and subacute toxicity of the extracts

The antiproliferative effects of Marrubium vulgare, and toxicity screening in zebrafish embryos

Consider the medicinal usefulness and ethnomedicinal uses referring to Marrubium vulgare; the CH3OH extract of whole plant was investigated for the antiproliferative, effect and toxicological screening. Its antiproliferative effect was evaluated against A549 (lung), HepG2 (Liver), MDA-MB-231 (breast) and MCF-7 cancer cell-lines. Doxorubicin was used as a positive control. Toxicological evaluation of the Marrubium vulgare methanol extract (MVM) was carried out in zebrafish embryos. The MVM showed more effective inhibition against MCF-7and MDA-MB-231 breast-cancer cells. The IC50 value ranged from 43.5 to 223.5 μg/mL. In term of IC50 MVM showed a strong antiproliferative effect averse to MDA-MB-231 and MCF-7 in terms of IC50 values (43.5 and 46.5 μg/mL respectively). Lethal concentration of MVM in zebrafish embryos remained 5 µg/ml. The results obtained from zebrafish embryos tests indicates that the extract is toxic at some level and should be used carefully or avoid it during the pregnancy

GC-MS profile of extracts of an endophytic fungus Alternaria and evaluation of its anticancer and antibacterial potentialities

Using microbial endophytes to produce bioactive compounds is a reliable scientific method. This investigation aimed to use the Acacia plant for isolating an endophytic fungal strain that has a bio-ability to produce a bio-crude extract. This study also encompassed the assessment of the extract’s biological efficacy as an antibacterial and anticancer agent. Samples of the Acacia plant were collected from “Shuaib Huraymila,” in Riyadh, Saudi Arabia. The isolation and identification of fungal endophytes was done, and then, the production of crude extract was performed using the isolated endophytes. The profile gas chromatography-mass spectroscopy of the extract was determined, followed by the assessment of its biological activity against drug-resistant infections and cancer cells through in vitro examination. The findings showed that the fungal endophyte was Alternaria (Alternaria sorghi), according to internal transcribed spacer sequencing and basic local alignment search tool analysis. The minimum inhibitory concentrations of the extract were 9.1 and 4.5 mg/mL for methicillin-resistant Staphylococcus aureus and drug-resistant Candida auris, respectively, and the IC50% values were 46.6 and 23.7 mg/mL for MCF-7 and A549, respectively. The findings showed that this strain had no antagonistic action against Culex pipiens. This study concluded that the fungal endophyte isolated from the Acacia plant has the bio-ability to produce antimicrobial and anticancer agents

Synthesis, Characterization, and Anti-Cancer Activity of Some New N′-(2-Oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazones Derivatives

Eight novel N′-(2-oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazone derivatives 4a–h were synthesized and fully characterized by IR, NMR (1H-NMR and 13C-NMR), elemental analysis, and X-ray crystallography. The cyto-toxicity and in vitro anti-cancer evaluation of the prepared compounds have been assessed against two different human tumour cell lines including human liver (HepG2) and leukaemia (Jurkat), as well as in normal cell lines derived from human embryonic kidney (HEK293) using MTT assay. The compounds 3e, 3f, 4a, 4c, and 4e revealed promising anti-cancer activities in tested human tumour cells lines (IC50 values between 3 and 7 μM) as compared to the known anti-cancer drug 5-Fluorouracil (IC50 32–50 μM). Among the tested compounds, 4a showed specificity against leukaemia (Jurkat) cells, with an IC50 value of 3.14 μM, but this compound was inactive in liver cancer and normal cell lines

Assessment of the physiological markers, oxidative stress and neurotoxic effects of nematode Anisakis sp. on the Luciobarbus callensis (Teleosts, Cyprinids) in northeast of Algeria

Our study focused on the effect of parasites on the antioxidant system and their neurotoxic effect in Luciobarbus callensis (Teleosts, Cyprinids). In this context, cellular biomarkers, acetylcholinesterase (AChE), catalase (CAT), molecules H2O2 as well as morphophysiological markers (condition factor (FC), hepatosomatic index (HSI), splenosomatic index (SSI), viscerosomatic index (VSI) were analyzed in fish infested with L3 larvae of Anisakis sp., nematodes of marine organisms, captured in Lake Oubéira (Algeria). The results showed a significant decrease in AChE activities in the heart (68 % p < 0.05) and muscles (81.55 % p < 0.05) in infested fish compared to those recorded in reference fish. In contrast, splenic AChE levels were significantly induced. CAT levels were significantly decreased in the spleen (73 % p < 0.05) and intestine (56 % p < 0.05) of fish parasitized by Anisakis sp. compared to healthy fish. HSI and SSI were significantly higher in healthy fish. On the other hand, Anisakis sp. had no significant effect on FC and VSI at the time of sampling. This study suggests that antioxidant defense disorders (CAT), due to a direct inhibitory action of nematode toxic products on this molecule and an increase in ROS production in these animals, leading to a high pro-oxidant state (H2O2), causing neurological effects (AChE) with enlargement of the spleen and liver of infested barb. In this regard, monitoring the effect of parasitic infections on physiological and biochemical marker profiles can be a crucial means of assessing fish health under natural conditions; to ensure the conservation and sustainability of aquatic biodiversity, including fish farming and artificial production

Biological Screening of Newly Synthesized BIAN N-Heterocyclic Gold Carbene Complexes in Zebrafish Embryos

N-Heterocyclic carbene (NHC) metal complexes possess diverse biological activities but have yet to be extensively explored as potential chemotherapeutic agents. We have previously reported the synthesis of a new class of NHC metal complexes N-heterocyclic with acetate [IPr(BIAN)AuOAc] and chloride [IPr(BIAN)AuCl] ligands. In the experiments reported herein, the zebrafish embryos were exposed to serial dilutions of each of these complexes for 10–12 h. One hundred percent mortality was observed at concentrations ≥50 µM. At sub-lethal concentrations (10–30 µM), both compounds influenced zebrafish embryonic development. However, quite diverse categories of abnormalities were found in exposed embryos with each compound. Severe brain deformation and notochord degeneration were evident in the case of [IPr(BIAN)AuOAc]. The zebrafish embryos treated with [IPr(BIAN)AuCl] exhibited stunted growth and consequently had smaller body sizes. A depletion of 30%–40% glutathione was detected in the treated embryos, which could account for one of the possible mechanism of neurotoxicity. The fact that these compounds are capable of both affecting the growth and also compromising antioxidant systems by elevating intracellular ROS production implies that they could play an important role as a new breed of therapeutic molecules

The Antiproliferative and Apoptotic Effect of a Novel Synthesized S-Triazine Dipeptide Series, and Toxicity Screening in Zebrafish Embryos

Several derivatives containing morpholine/piperidine, anilines, and dipeptides as pending moieties were prepared using s-triazine as a scaffold. These compounds were evaluated for their anticancer activity against two human breast cancer cell lines (MCF-7 and MDA-MB-231), a colon cancer cell line (HCT-116), and a non-tumorigenic cell line (HEK 293). Tamoxifen was used as a reference. Animal toxicity tests were carried out in zebrafish embryos. Most of these compounds showed a higher activity against breast cancer than colon cancer. Compound 3a—which contains morpholine, aniline, and glycylglycinate methyl ester—showed a high level of cytotoxicity against MCF-7 cells with IC50 values of less than 1 µM. This compound showed a much lower level of toxicity against the non-tumorigenic HEK-293 cell line, and in the in vivo studies using zebrafish embryos. Furthermore, it induced cell cycle arrest at the G2/M phase, and apoptosis in MCF-7 cells. On the basis of our results, 3a emerges as a potential candidate for further development as a therapeutic drug to treat hormone receptor-positive breast cancer.The work was funded in part by the National Research Foundation (NRF) (# 105892 and Blue Sky’s Research Programme # 120386). This study was funded by the Deanship of Scientific Research, King Saud University, through the Vice Deanship of Scientific Research Chairs.Peer reviewe

Antiproliferative Illudalane Sesquiterpenes from the Marine Sediment Ascomycete Aspergillus oryzae

The new asperorlactone (1), along with the known illudalane sesquiterpene echinolactone D (2), two known pyrones, 4-(hydroxymethyl)-5-hydroxy-2H-pyran-2-one (3) and its acetate 4, and 4-hydroxybenzaldehyde (5), were isolated from a culture of Aspergillus oryzae, collected from Red Sea marine sediments. The structure of asperorlactone (1) was elucidated by HR-ESIMS, 1D, and 2D NMR, and a comparison between experimental and DFT calculated electronic circular dichroism (ECD) spectra. This is the first report of illudalane sesquiterpenoids from Aspergillus fungi and, more in general, from ascomycetes. Asperorlactone (1) exhibited antiproliferative activity against human lung, liver, and breast carcinoma cell lines, with IC50 values &lt; 100 µM. All the isolated compounds were also evaluated for their toxicity using the zebrafish embryo model