Design, Synthesis and In Vitro Anti-Cancer Evaluation of Novel Derivatives of 2-(2-Methyl-1,5-diaryl-1H-pyrrol-3-yl)-2-oxo-N-(pyridin-3- yl)acetamide

2020 ◽  
Vol 16 (3) ◽  
pp. 340-349
Author(s):  
Ebrahim S. Moghadam ◽  
Farhad Saravani ◽  
Ernest Hamel ◽  
Zahra Shahsavari ◽  
Mohsen Alipour ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Peripheral Neuropathy ◽  
Cell Line ◽  
Normal Cell ◽  
Caspase 3 ◽  
Annexin V ◽  
Normal Cell Line ◽  
Anti Cancer ◽  
Mcf 7

Objective: Several anti-tubulin agents were introduced for the cancer treatment so far. Despite successes in the treatment of cancer, these agents cause toxic side effects, including peripheral neuropathy. Comparing anti-tubulin agents, indibulin seemed to cause minimal peripheral neuropathy, but its poor aqueous solubility and other potential clinical problems have led to its remaining in a preclinical stage. Methods: Herein, indibulin analogues were synthesized and evaluated for their in vitro anti-cancer activity using MTT assay (on the MCF-7, T47-D, MDA-MB231 and NIH-3T3 cell lines), annexin V/PI staining assay, cell cycle analysis, anti-tubulin assay and caspase 3/7 activation assay. Results: One of the compounds, 4a, showed good anti-proliferative activity against MCF-7 cells (IC50: 7.5 μM) and low toxicity on a normal cell line (IC50 > 100 μM). All of the tested compounds showed lower cytotoxicity on normal cell line in comparison to reference compound, indibulin. In the annexin V/PI staining assay, induction of apoptosis in the MCF-7 cell line was observed. Cell cycle analysis illustrated an increasing proportion of cells in the sub-G-1 phase, consistent with an increasing proportion of apoptotic cells. No increase in G2/M cells was observed, consistent with the absence of anti-tubulin activity. A caspase 3/7 assay protocol showed that apoptosis induction by more potent compounds was due to activation of caspase 3. Conclusion: Newly synthesized compounds exerted acceptable anticancer activity and further investigation of current scaffold would be beneficial.

Design, Synthesis and Bioactivity Evaluation of Novel Chalcone Derivatives Possessing Tryptophan Moiety with Dual Activities of Anti-cancer and Partially Restoring the Proliferation of Normal Kidney Cells Pre-treated with Cisplatin

2021 ◽  
Vol 21 ◽  
Author(s):  
Meng He ◽  
Mingjun Yu ◽  
Chao Li ◽  
Xiaoming Meng ◽  
Jiamin Su ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Line ◽  
Normal Cell ◽  
Kidney Cells ◽  
Normal Kidney ◽  
Normal Cell Line ◽  
Chalcone Derivatives ◽  
Anti Cancer ◽  
Anti Inflammatory ◽  
Cancer Activity

Background: Chalcone is a broad-spectrum natural product with anti-cancer and anti-inflammatory activities. However, low potency, low selectivity, and serious side effects limit its druggability. L-Tryptophan is an essential precursor molecule of an anti-cancer active substance. Also, the indole moiety inhibits the proliferation of tumor cells by binding to colchicine sites. A decrease in kidney cell activity caused by kidney inflammation is the primary side effect of cancer therapy. Objective: The purpose of this work was to design, synthesize, and perform bioactivity evaluation of novel chalcone derivatives possessing tryptophan moiety with dual activities of anti-cancer and partially restoring the proliferation of normal kidney cells pre-treated with cisplatin. Methods: A series of novel chalcone derivatives possessing tryptophan moiety (5a-5g, 6a-6o) were designed, synthesized, and evaluated for anti-cancer activity against four cancer cell lines (gastric (HGC-27), colon (HCT-116), prostate (PC-3), and lung (A549)), and a human normal cell line (gastric mucosal epithelial (GES-1)). The activity of restoring the proliferation of normal kidney cells pre-treated with cisplatin was evaluated by MTT assay. Cell cycle, apoptosis, and apoptosis proteins (Bax and Bcl-2) were used to evaluate the anti-cancer mechanism of the most potent compound. Moreover, a docking study was performed to explain the high anti-cancer activity of 6n. The expressions of TNF-α, IL-6, and MCP-1 were detected by ELISA. Results: Most of the compounds exhibited high anti-cancer activity against the HGC-27 cell line and exhibited low toxicity against the normal cell line. Based on three rounds of a structure optimization, 6n was discovered as the most potent compound against HGC-27 cells with an IC50 value of 2.02 μM and an SI value of 28.47. Further studies demonstrated that 6n could induce cell cycle arrest at the G2/M phase and the apoptosis of the HGC-27 cell line by reducing the expression of Bcl-2 and improving the expression level of Bax. Molecular docking result displayed 6n bound to the colchicine site. At the same time, 6n also exhibited moderate activity of restoring the proliferation of normal kidney cells pre-treated with cisplatin by reducing the expression of inflammatory substances. Conclusion: Our findings collectively suggested that 6n should be further studied as a potential anti-cancer agent that could partially restore the proliferation of normal kidney cells pre-treated with cisplatin in gastric cancer patients by an anti-inflammatory pathway.

Novel 1,2,3-Triazole-functionalized pyrido[3',2':4,5]furo[3,2-d]pyrimidin- 4(3H)-one Derivatives: Synthesis, Anticancer Activity, CoMFA and CoMSIA Studies

2020 ◽  
Vol 17 (12) ◽  
pp. 969-978
Author(s):  
Balakishan Vadla ◽  
Sailu Betala
Keyword(s):  
Anticancer Activity ◽  
Cell Line ◽  
Normal Cell ◽  
Rational Design ◽  
Human Cancer ◽  
Strong Basis ◽  
Hek 293 ◽  
Normal Cell Line ◽  
Human Cancer Cell Lines ◽  
Mcf 7

A series of novel triazole functionalized pyrido [3',2':4,5] furo[3,2-d] pyrimidin-4 (3H)-one derivatives 7a-p were prepared from ethyl furo[2,3-b]pyridine-2-carboxylate 3 on reaction with ammonia to afford furo[2,3-b]pyridine-2-carboxamide 4. This compound, on reaction with triethyl orthoformate TEOF, gave compound 5. Compound 5 on propargylation, followed by a reaction with substituted aryl azides under Sharpless reaction conditions, furnished triazole tagged pyrido [3',2':4,5]furo[3,2-d] pyrimidin-4(3H)-one derivatives. All the products 7a-p were screened against four human cancer cell lines, such as HeLa - Cervical cancer (CCL-2), COLO 205- Colon cancer (CCL-222), HepG2- Liver cancer (HB-8065), and MCF7 - Breast cancer (HTB-22) and one normal cell line (HEK 293). Compounds 7b, 7n, 7o and 7p, which showed promising anticancer activity, were identified and found to be non-toxic to normal cell line. Studies for HeLa, COLO205, HepG2, and MCF-7 using CoMFA and CoMSIA were carried out . Models from 3D-QSAR provided a strong basis for future rational design of more active and selective HeLa, COLO205, HepG2, and MCF-7 cell line inhibitors.

Targeting Aminopeptidases by Tosedostat (TST) (CHR2797), Alone and with LBH589, Induces Significant Cytotoxicity Against Human Multiple Myeloma (MM) Cells

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1847-1847
Author(s):  
Chirag Acharya ◽  
Mike Y Zhong ◽  
Daniel Tannenbaum ◽  
Michelle Chen ◽  
Matt Ma ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Caspase 3 ◽  
Combined Treatment ◽  
Single Agent ◽  
Annexin V ◽  
Novel Approach ◽  
Human Multiple Myeloma ◽  
Induced Apoptosis ◽  
G1 Cells

Abstract Abstract 1847 Aminopeptidases (AP) are necessary for the growth and development of malignant cells and have a selectively important role in the maintenance of intracellular amino acid (AA) levels in neoplastic cells. CHR2797 is a novel, low nanomolar inhibitor of the M1 family of AP, a group of metalloenzymes containing a central Zn2+ ion. CHR2797 has antiproliferative and apoptotic effects against MM in vitro by inducing the AA deprivation response (AADR). TST, an oral, chronically administered agent with a good safety profile has demonstrated activity in patients with relapsed/refractory AML and is currently under study as part of combination therapy for untreated elderly patients with AML. At the epigenetic regulatory level, Zn-dependent histone deacetylase (HDAC) cause the deacetylation of histone and non-histone cellular proteins which are critical for gene expression, inducing apoptosis and cell cycle arrest in cancer cells. LBH589 (Panobinostat) is an established pan-HDAC inhibitor with potent in vitro anti-cancer activity in many hematological malignancies. The clinical efficacy of Panobinostat is currently being studied in several Phase II/III clinical trials with particular promise seen in the treatment of MM. Here we examined the potential therapeutic effect of CHR2797, alone and with LBH589, against MM cells. Using MTS and CTG assays, CHR2797, at clinically achievable concentrations, decreased survival and proliferation in MM1S and IL-6-dependent ANBL6 cells, in the presence or absence of bone marrow stromal cells following 72 hours incubation. CHR2797 induces apoptosis in MM cells via activation of Caspase 3/7 and 9 but not Caspase 8. Significantly, CHR2797 (10 μM) induced apoptosis in patient MM cells, as seen by % of annexin V and PI from 22 + 1.5% to 39 + 2.3% after 48h incubation. Combined treatment with CHR2797 and LBH589 in MM cells (MM1S, ANBL6, and INA6) further reduced cell viability following 72 hour incubation when compared with CHR2797 treatment alone, as determined by CTG viability luminescent assay. Both drugs together also augmented growth inhibitory effects when compared with single agent alone, after 72 hours incubation followed by MTS assay. Importantly, the combination of both drugs increased caspase 3/7- & 9-mediated apoptosis than CHR2797 alone in these MM cells following 24h-treatment. Cell cycle analysis (CHR2797 at 1μM; LBH589 at 1 nM) showed an increased growth arrest in G0/G1 cells in MM1R cells treated with both drugs versus CHR2797 alone after 24 hours: 68.5±3.3% versus 36±2.5%. Furthermore, CHR2797 inhibited anti-apoptotic protein Mcl-1 in MM1R and U266 MM cells by immunoblottings. Combined treatment with CHR2797 and LBH589 further blocked Mcl-1 when compared with either treatment alone after 24 hours incubation. Together, these results show that the combination of CHR2797 and LBH589 enhanced anti-myeloma effects when compared with either drug alone. This combination, which also has the potential of being without overlapping clinical toxicities, provides a promising novel approach to anti-myeloma therapy. Disclosures: Singer: Cell Therapeutics, Inc: Employment, Equity Ownership. Richardson:Novartis: Membership on an entity's Board of Directors or advisory committees.

scholarly journals In vitro anticancer activity of methanolic extract of Granulocystopsis sp., a microalgae from an oligotrophic oasis in the Chihuahuan desert

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8686
Author(s):  
Faviola Tavares-Carreón ◽  
Susana De la Torre-Zavala ◽  
Hector Fernando Arocha-Garza ◽  
Valeria Souza ◽  
Luis J. Galán-Wong ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Normal Cell ◽  
Chihuahuan Desert ◽  
Methanolic Extract ◽  
Membrane Integrity ◽  
Skin Melanoma ◽  
Normal Cell Line

With the purpose of discovering new anticancer molecules that might have fewer side effects or reduce resistance to current antitumor drugs, a bioprospecting study of the microalgae of the Cuatro Cienegas Basin (CCB), an oasis in the Chihuahuan desert in Mexico was conducted. A microalgae was identified as Granulocystopsis sp. through sequencing the rbcL gene and reconstruction of a phylogenetic tree, and its anticancer activities were assessed using various in vitro assays and different cell lines of human cancers, including lung, skin melanoma, colorectal, breast and prostatic cancers, as well as a normal cell line. The values of IC50 of the microalgae methanolic extract using the MTT assay were lower than 20 μg/ml, except that in the lung cancer line and the normal cell line. In vitro, the microalgae extract caused the loss of membrane integrity, monitored by the trypan blue exclusion test and exhibited marked inhibition of adhesion and cell proliferation in cancer cell lines, through the evaluation of the clonogenic assay. Also, typical nuclear changes of apoptotic processes were observed under the microscope, using the dual acridine orange/ethidium bromide fluorescent staining. Finally, the microalgae extract increased the activity of caspases 3 and 7 in skin melanoma, colon, breast and prostate cancer cells, in the same way as the apoptotic inductor and powerful antitumoral drug, doxorubicin. This study shows the anticancer activity from Granulocystopsis sp., a microalgae isolated from the CCB.

scholarly journals Activity Anticancer n-hexane Fraction of Cyperus Rotundus l. Rhizome to Breast Cancer MCF-7 Cell Line

2019 ◽  
Vol 7 (22) ◽  
pp. 3904-3906
Author(s):  
Delisma Simorangkir ◽  
Masfria Masfria ◽  
Urip Harahap ◽  
Denny Satria
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Anticancer Activity ◽  
Cell Line ◽  
Vero Cells ◽  
Cyperus Rotundus ◽  
Hexane Fraction ◽  
Synthetic Drugs ◽  
Mcf 7

BACKGROUND: Cancer is one of the causes of morbidity and mortality worldwide. Breast cancer is one of the most common types of cancer in Indonesia. Failures that often occur in the treatment of cancer primarily through chemotherapy, synthetic drugs that have side effects include anemia, alopecia, cardiotoxic and hepatotoxic due to low anti-cancer selectivity and unclear carcinogenesis process. Cyperus rotundus L. rhizome is one of the medicinal plants that potential enough to be developed as an anticancer agent. AIM: The aim of this study was to anticancer activity n-hexane fraction Cyperus rotundus L. rhizomes to breast cancer MCF-7 cell line in vitro. METHODS: Cyperus rutundus L. rhizomes powder was extracted ethanol by percolation then fractionated with n-hexane. Phytochemical screening was then carried out. The cytotoxic activity of the n-hexane fraction was determined by observing this extract on MCF-7 cells using the (3- (4,5-dimethylimidazole-2-il) -2,5-diphenyl tetrazolium bromide) (MTT). Selectivity index (IS) of normal cells (Vero cells). Cell cycle and apoptosis induction were analyzed by flow cytometry. RESULTS: The result showed that the fraction n-hexane Cyperus rutundus L. rhizome has anticancer activity against breast cancer MCF-7 cells with accumulation cell cycle in the G0-G1 phase and through induction of apoptosis. CONCLUSION: The n-hexane fraction Cyperus rotundus L. rhizome has potent anticancer activity.

Synthesis, Characterization and Anti-hepatoma Activity of New Hederagenin Derivatives

2020 ◽  
Vol 20 (3) ◽  
pp. 252-257
Author(s):  
Xiao Liu ◽  
Lu Sun ◽  
Qing-Hua Liu ◽  
Bao-Quan Chen ◽  
Yu-Ming Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Line ◽  
Hepg2 Cell ◽  
Normal Cell ◽  
Biological Significance ◽  
Cancer Cell Line ◽  
Human Hepatocellular Carcinoma ◽  
Hepg2 Cell Line ◽  
Normal Cell Line

Background: Based on the biological significance of hederagenin-type saponins found in our previous investigation, a series of new hederagenin derivatives were designed and synthesized. Methods : Their in vitro antiproliferative activities were evaluated against the HepG2 liver cancer cell line and normal cell line L929 by MTT assay. Results: The preliminary bioassay results demonstrated that all the tested compounds 1-7 showed potent anti-hepatoma activities, and some compounds exhibited better effects than 5-fluorouracil against human hepatocellular carcinoma HepG2 cell line. Furthermore, compound 5 showed a significant antihepatoma activity against HepG2 cells with an IC50 value of 1.88 µM. Besides, all of the tested compounds showed a low cytotoxic effect against the normal cell line L929. Conclusion: All the compounds 1-7 displayed superior selectivity against human hepatocellular carcinoma HepG2 cell line, and the results suggest that the structural modifications of C ring on the hederagenin backbone are vital for modulating anti-hepatoma activities.

ANTIPROLIFERATIVE EFFECT OF Dendrophthoe pentandra EXTRACTS TOWARDS HUMAN BREAST ADENOCARCINOMA CELLS (MCF-7)

2015 ◽  
Vol 77 (2) ◽  
Author(s):  
Nik Aina Syazana Nik Zainuddin ◽  
Mohd Dasuki Sul’ain
Keyword(s):  
Ethyl Acetate ◽  
Cell Line ◽  
Cancer Cell ◽  
Normal Cell ◽  
Antiproliferative Effect ◽  
Breast Adenocarcinoma ◽  
Screening Assay ◽  
Remarkable Effect ◽  
Mcf 7

Dendrophthoe pentandra (DP) is a semi-parasitic plant. Previous studies showed that this plant possessed diverse medicinal properties. The present study was carried out to determine antiproliferative activity of various DP crude extracts. Extracts of petroleum ether, diethyl ether, chloroform, ethyl acetate and methanol, have been evaluated through IC50 value, which defined by the concentration of drug that is required for the inhibition of 50% of cell population in vitro. The determination of percentage cell viability was conducted by using MTT assay. The screening assay involved the use of malignant cell line MCF-7 (breast cancer cell) whereas the normal cell line was L929 (connective cell). The control drug used was tamoxifen. The ethyl acetate and methanol extracts were found to be more effective against MCF-7 cancer cell lines compared to the others. All extracts showed no remarkable effect against normal cell L929 with IC50 values more than 100 µg/mL. In contrast to tamoxifen, all extracts showed less cytotoxicity effect towards normal cells. The data obtained from this study provide notable preliminary information on the cytotoxic/antiproliferative effect of different DP extracts and further study should be carried out to isolate the active compound of the most potential DP extracts.

Cytotoxicity Assay of Agaricus Bisporus Extract , Oxaliplatin and Combination of both on Melanoma-B16 and Vero-101 Cell line:An in Vitro study

2020 ◽  
pp. 10-14
Keyword(s):  
Cell Line ◽  
Crude Extract ◽  
Normal Cell ◽  
In Vitro Study ◽  
Cytotoxicity Assay ◽  
Inhibition Rate ◽  
Normal Cells ◽  
Normal Cell Line ◽  
Melanoma B16

The present study included extracted Agaricus bispours and estimated proteins and carbohydrates amount in extract then assessment activity of methanolic crude extract of medicinal mushroom A. bisporus as in vitro anticancer by using melanoma-B16 cell line ,and compared with chemotherapy Oxaliplatin and approved reduction toxic effect of chemotherapy on normal cells when exposed to combination between chemotherapy and mushroom extract on normal vero-101 cell line. Proteins and carbohydrate estimation results referred to there are about 219.33 and 412.98 µg/ml respectively. The results showed that inhibition rate of melanoma-B16 cell line was about 82.15% according to cytotoxicity assay test by crystal violate when treated these cells by methanol crude extract of A. bisporus at 1000 mg/ml .But the cytotoxicity assay of using chemotherapy oxaliplatin on melanoma-B16 at 100 mg/ml results appeared that the inhibition rate was 64.52%. The cytotoxicity assay of combination between methanolic crude extract of A.bisporus 1000 mg/ml and oxaliplatin 100 mg/ml results the inhibition rate was 70.04% on melanoma B-16 cell line.Crystal violate cytotoxicity assay of treatments on normal vero-101 cell line results were revealed that non significantly inhibition of A.bisporus extract on normal cells only 5.37%.While chemotherapy oxaliplatin have inhibition rate on vero-101 normal cell line about 65% ,While the combination treatment cytotoxicity assay on vero-101 normal cell line showed that inhibition rate was reduced to 20.35% comparing with cancer cell which was about 65.3%

A Novel Celecoxib Derivative, OSU03012, Induces Cytotoxicity in Primary CLL Cells and Transformed B-Cell Lymphoma Via a Caspase and Bcl-2 Independent Mechanism.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3471-3471
Author(s):  
Amy Johnson ◽  
Lisa Smith ◽  
Jiuxiang Zhu ◽  
Nyla Heerema ◽  
Sara Guster ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Cell Line ◽  
Mechanism Of Action ◽  
Caspase 3 ◽  
Annexin V ◽  
In Vitro Activity ◽  
Caspase 9 ◽  
Over Expression

Abstract Chronic lymphocytic leukemia (CLL) is an incurable adult leukemia characterized by disrupted apoptosis. While the majority of patients with CLL are asymptomatic at diagnosis, most progress and require therapy. Identification of new targets and therapeutic agents is therefore a high priority for the treatment of CLL. Synthetic chemistry yielded derivatives of the COX-2 inhibitor, celecoxib, with increased ability to induce apoptosis in the 1–10 μ M range in prostate cancer cells, a similar proposed mechanism of action, and increased in vivo activity in a murine prostate cancer xenograft model. Based upon these data, a Rapid Access to Intervention Development (RAID) proposal is underway to generate OSU03012 for clinical studies in prostate cancer. In addition, we are examining the biologic effects of these new agents in primary CLL cells and lymphoblastic cell lines, showing a novel mechanism of cell killing independent of caspase activation and bcl-2 over-expression. To determine the in vitro activity against CLL cells, 11 CLL patient PBMCs were incubated in various concentrations of OSU03012. The LC50 at 24 hrs was 7.12μM and decreased to 5.45μM at 72 hrs. We show both early (annexin-V positive) and late (both annexin-V/PI positive) apoptosis concurrent with loss of mitochondrial membrane potential typical of apoptosis. These data suggest OSU03012 is highly cytotoxic toward CLL cells in vitro at doses well below those attainable without toxicity in a murine model. Additionally, we show that OSU03012 mediates apoptosis by activation of the intrinsic, mitochondrial pathway of apoptosis but also activates alternative caspase independent cell death pathways. CLL cells from 8 patients were incubated in 10μM OSU03012 for 24 hrs and assessed for caspase-3 and PARP. Immunoblots reveal a dose dependent increase in active caspase-3 concurrent with a decrease in the pro-form. This occurred concurrently with the appearance of the 85 kD cleaved product of PARP that is a known downstream target of caspase-3. In the same 8 patient lysates we saw no change in the inactive pro-form of caspase-8, but consistent processing of caspase-9. These data suggest that OSU03012 in part utilizes the intrinsic pathway of apoptosis to promote CLL cell death. Incubation of CLL cells with z-VAD-fmk and OSU03012 did not abrogate cell death, but eliminated processing of caspase-9, caspase-3 and PARP, suggesting that this agent also activates caspase independent mechanisms of cell death. Given the caspase dependent and independent pathways utilized by OSU03012, we assessed the dependence of cell death on bcl-2 expression. Here we show that bcl-2 over-expression in the 697 lymphoblastic cell line greatly diminishes the apoptosis observed with fludarabine, but potent apoptosis is equally observed with OSU03012 compared to the empty vector cell line. Furthermore, in the bcl-2 over-expressing cell line, caspase-3 and PARP cleavage was not observed despite equivalent apoptosis supporting further multiple mechanisms of cell killing induced by OSU03012. In summary, OSU03012 is an oral bioavailable therapeutic agent that has potent in vitro activity against primary CLL cells. This cytotoxicity is mediated by both caspase dependent and independent pathways and can overcome bcl-2 over-expression. These data provide support for further investigation of the mechanism of action of OSU03012 in CLL cells and performance of early Phase I studies in CLL as part of the RAID process.

scholarly journals Effect of Sterols Isolated fromMyrtillocactus geometrizanson Growth Inhibition of Colon and Breast Cancer Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Mario Augusto Bolaños-Carrillo ◽  
Jose Luis Ventura-Gallegos ◽  
Arturo David Saldivar-Jiménez ◽  
Alejandro Zentella-Dehesa ◽  
Mariano Martínez-Vázquez
Keyword(s):  
Cell Cycle ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Biological Activities ◽  
Annexin V ◽  
Parp Cleavage ◽  
Dependent Manner ◽  
Cycle Dependent ◽  
Mcf 7

Objective. To explore the effect of peniocerol and macdougallin on HCT-15 and MCF-7 cells proliferation, cell cycle, apoptosis, and PARP cleavage.Methods. HCT-15 and MCF-7 cells were treated with various concentrations of peniocerol and macdougallin (10–80 μM) during 24 or 48 h. Crystal Violet Assay was used to evaluate the inhibition effect. Cell cycle regulation was examined by a propidium iodide method. Cell apoptosis was detected through both Annexin–V FLUOS/PI double-labeled cytometry assays and Western blot was applied to assess PARP cleavage.Results. Peniocerol and macdougallin induced growth inhibition and apoptosisin vitroin a time- and dose-dependent manner. Moreover, peniocerol and macdougallin induced arrest of cell cycle-dependent manner and increased the proportion of cells in G0/G1phase. PARP cleavage in HCT-15 and MCF-7 cells was induced by treatment with peniocerol and macdougallin after 36 hours.Conclusions. Our results showed that the mechanism of cytotoxicity displayed by peniocerol and macdougallin is related to cell cycle arrest and apoptosis in both cell lines. This is a significant observation because it helps to understand the way some oxysterols isolated fromMyrtillocactus geometrizansdevelop their biological activities against cancer cells.

Sign in / Sign up

Export Citation Format

Share Document