scholarly journals New Oleoyl Hybrids of Natural Antioxidants: Synthesis and In Vitro Evaluation as Inducers of Apoptosis in Colorectal Cancer Cells

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1077
Author(s):  
Gabriele Carullo ◽  
Sarah Mazzotta ◽  
Adrian Koch ◽  
Kristin M. Hartmann ◽  
Oliver Friedrich ◽  
...  
Keyword(s):  
Healthy Lifestyle ◽  
Apoptotic Cell ◽  
Human Cancer ◽  
Natural Antioxidants ◽  
In Vitro Assays ◽  
Human Cancer Cell Lines ◽  
Cancer Management ◽  
Anti Cancer ◽  
Colorectal Cancer Cells

Nowadays, the beneficial role of a healthy lifestyle, particularly emphasizing the quality of foods and cancer management, is accepted worldwide. Polyphenols and oleic acid play a key role in this context, but are still scarcely used as anti-cancer agents due to their bio-accessibility limits. Therefore, we aimed to synthesize a set of new oleoyl-hybrids of quercetin, morin, pinocembrin, and catechin to overcome the low bioavailability of polyphenols, throughout a bio-catalytic approach using pancreatic porcine lipase as a catalyst. The in vitro assays, using a wide panel of human cancer cell lines showed, mainly for two novel regioisomer oleoyl-hybrids of quercetin, a remarkable increase in apoptotic cell populations. We suggested that the DNA damage shown as ɣH2AX signals might be the major cause of apoptotic cell death. Finally, we demonstrated convincing data about two novel polyphenol-based hybrids displaying a highly selective anti-cancer cytotoxicity and being superior compared to their reference/parental compounds.

The Design and Synthesis of Novel Phenothiazine Derivatives as Potential Cytotoxic Agents

2019 ◽  
Vol 17 (1) ◽  
pp. 57-67
Author(s):  
Yepeng Luan ◽  
Jinyi Liu ◽  
Jianjun Gao ◽  
Jinhua Wang
Keyword(s):  
Cell Lines ◽  
High Efficiency ◽  
Human Cancer ◽  
Human Tumor ◽  
Cytotoxic Agents ◽  
Cancer Drug ◽  
Human Cancer Cell Lines ◽  
Incidence And Mortality ◽  
Anti Cancer

Background: Cancer incidence and mortality have been increasing and cancer is still the leading cause of death all over the world. Despite the enormous progress in cancer treatment, many patients died of ineffective chemotherapy and drug resistance. Therefore, the design and development of anti-cancer drugs with high efficiency and low toxicity is still one of the most challenging tasks. Tricyclic heterocycles, such as phenothiazine, are always important sources of scaffolds for anti-cancer drug discovery. Methods: In this work, ten new urea-containing derivatives of phenothiazine coupled with different kinds of amine motifs at the endpoint through a three carbon long spacer were designed and synthesized. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR and HRMS. All the synthesized compounds were tested for their antitumor activity in vitro against the proliferation of PC-3 cells, and the compounds with best potency entered further cytotoxicity evaluations against other 22 human tumor cell lines. Mechanism was also studied. Results: From all data, it showed that among all 10 target compounds, TTi-2 showed the best effect in inhibiting the proliferation of 23 human cancer cell lines while TTi-2 without obvious inhibitory effect on normal cell. Furthermore, our results also showed that TTi-2 could inhibit migration, invasion and colony formation of MDA-MB-231 cells. Finally, TTi-2 can induce arrest of cell cycle at G0/G1 phase and cell apoptosis by activating the caspase 3 activity. Conclusion: All these results suggested that TTi-2 might be used as a promising lead compound for anticancer drug development.

scholarly journals Identification of a Potent Cytotoxic Pyrazole with Anti-Breast Cancer Activity That Alters Multiple Pathways

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 254
Author(s):  
Denisse A. Gutierrez ◽  
Lisett Contreras ◽  
Paulina J. Villanueva ◽  
Edgar A. Borrego ◽  
Karla Morán-Santibañez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Human Cancer ◽  
Stress Protein ◽  
In Vitro Assays ◽  
Parp Cleavage ◽  
Human Cancer Cell Lines ◽  
Microtubule Disruption ◽  
Tnbc Cell

In this study, we identified a novel pyrazole-based derivative (P3C) that displayed potent cytotoxicity against 27 human cancer cell lines derived from different tissue origins with 50% cytotoxic concentrations (CC50) in the low micromolar and nanomolar range, particularly in two triple-negative breast cancer (TNBC) cell lines (from 0.25 to 0.49 µM). In vitro assays revealed that P3C induces reactive oxygen species (ROS) accumulation leading to mitochondrial depolarization and caspase-3/7 and -8 activation, suggesting the participation of both the intrinsic and extrinsic apoptotic pathways. P3C caused microtubule disruption, phosphatidylserine externalization, PARP cleavage, DNA fragmentation, and cell cycle arrest on TNBC cells. In addition, P3C triggered dephosphorylation of CREB, p38, ERK, STAT3, and Fyn, and hyperphosphorylation of JNK and NF-kB in TNBC cells, indicating the inactivation of both p38MAPK/STAT3 and ERK1/2/CREB signaling pathways. In support of our in vitro assays, transcriptome analyses of two distinct TNBC cell lines (MDA-MB-231 and MDA-MB-468 cells) treated with P3C revealed 28 genes similarly affected by the treatment implicated in apoptosis, oxidative stress, protein kinase modulation, and microtubule stability.

Cytotoxicity and Anti-cancer Activity of the Genus Achillea L.

2020 ◽  
Vol 27 (41) ◽  
pp. 6910-6925 ◽  
Author(s):  
Konstantina Papakosta ◽  
Maria-Eleni Grafakou ◽  
Christina Barda ◽  
Ioannis V. Kostopoulos ◽  
Ourania Tsitsilonis ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Traditional Medicine ◽  
Human Cancer ◽  
Biological Activities ◽  
Northern Greece ◽  
Human Cancer Cell Lines ◽  
Anti Cancer ◽  
Analgesic Agents ◽  
Selection Of

Background: The genus Achillea L. is rich in bioactive sesquiterpenes and flavonoids; most of the studied species exhibit several biological activities and are used as emmenagogue, wound healing and analgesic agents. Some species are also used in local folklore medicine. Objective: Following a literature survey, we discuss the anti-cancer properties of Achillea species, taking into consideration ethnopharmacological data on their use in traditional medicine for the treatment of cancer. In addition, we screened extracts and isolated secondary metabolites from A. coarctata for cytotoxicity, upon information based on local traditional medicine. The plant was collected in Kozani (Northern Greece), where it is locally used for treating gastrointestinal disorders, including stomach cancer. Methods: A selection of the relevant data was performed through a search in PubMed, Scopus, Google Scholar and Science Direct databases. In addition, extracts and isolated compounds from A. coarctata were tested for their in vitro activity against the human cancer cell lines MCF-7 and HeLa. Conclusion: The genus Achillea L. is a valuable source of bioactive secondary metabolites. The most significant outcome of the investigation of medicinal plants is the documentation and the assessment of the traditional information and its use and perspectives in the light of modern pharmacology.

scholarly journals Synthesis and Biological Screening of New Cyano-Substituted Pyrrole Fused (Iso)Quinoline Derivatives

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 2066
Author(s):  
Maria Cristina Al-Matarneh ◽  
Roxana-Maria Amărandi ◽  
Ionel I. Mangalagiu ◽  
Ramona Danac
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
In Vitro Assays ◽  
Biological Screening ◽  
Human Cancer Cell Lines ◽  
Breast And Prostate Cancer

Several new cyano-substituted derivatives with pyrrolo[1,2-a]quinoline and pyrrolo[2,1-a]isoquinoline scaffolds were synthesized by the [3 + 2] cycloaddition of (iso)quinolinium ylides to fumaronitrile. The cycloimmonium ylides reacted in situ as 1,3-dipoles with fumaronitrile to selectively form distinct final compounds, depending on the structure of the (iso)quinolinium salt. Eleven compounds were evaluated for their anticancer activity against a panel of 60 human cancer cell lines. The most potent compound 9a showed a broad spectrum of antiproliferative activity against cancer cell lines representing leukemia, melanoma and cancer of lung, colon, central nervous system, ovary, kidney, breast and prostate cancer. In vitro assays and molecular docking revealed tubulin interaction properties of compound 9a.

scholarly journals Self-assembly of an anion receptor with metal-dependent kinase inhibition and potent in vitro anti-cancer properties

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Simon J. Allison ◽  
Jaroslaw Bryk ◽  
Christopher J. Clemett ◽  
Robert A. Faulkner ◽  
Michael Ginger ◽  
...  
Keyword(s):  
Self Assembly ◽  
Human Cancer ◽  
Cancer Therapeutics ◽  
Selective Inhibition ◽  
Human Cancer Cell Lines ◽  
Cellular Processes ◽  
Self Assembling ◽  
Anti Cancer ◽  
Anionic Species

AbstractOne topical area of supramolecular chemistry is the binding of anionic species but despite the importance of anions in diverse cellular processes and for cancer development, anion receptors or ‘binders’ have received little attention as potential anti-cancer therapeutics. Here we report self-assembling trimetallic cryptands (e.g. [L2(Metal)3]6+ where Metal = Cu2+, Zn2+ or Mn2+) which can encapsulate a range of anions and which show metal-dependent differences in chemical and biological reactivities. In cell studies, both [L2Cu3]6+ and [L2Zn3]6+ complexes are highly toxic to a range of human cancer cell lines and they show significant metal-dependent selective activity towards cancer cells compared to healthy, non-cancerous cells (by up to 2000-fold). The addition of different anions to the complexes (e.g. PO43ˉ, SO42ˉ or PhOPO32ˉ) further alters activity and selectivity allowing the activity to be modulated via a self-assembly process. The activity is attributed to the ability to either bind or hydrolyse phosphate esters and mechanistic studies show differential and selective inhibition of multiple kinases by both [L2Cu3]6+ and [L2Zn3]6+ complexes but via different mechanisms.

Potential Anti-Cancer Activities of Furanodiene, A Sesquiterpene from Curcuma wenyujin

2009 ◽  
Vol 37 (03) ◽  
pp. 589-596 ◽  
Author(s):  
Xiu-Yan Sun ◽  
Yan-Ping Zheng ◽  
Dong-Hai Lin ◽  
Hui Zhang ◽  
Feng Zhao ◽  
...  
Keyword(s):  
Essential Oil ◽  
Active Component ◽  
Human Cancer ◽  
Uterine Cervical Cancer ◽  
Primary Component ◽  
Inhibitory Effects ◽  
Human Cancer Cell Lines ◽  
Anti Cancer

Furanodiene is a sesquiterpene extracted from the essential oil of the rhizome of Curcuma wenyujin Y.H. Chen et C. Ling (Wen Ezhu). Furanodiene is the primary component in Wen Ezhu's essential oil, accounting for more than 20% by weight. In vitro, MTT assay was used to compare the inhibitory effects of furanodiene and Wen Ezhu's essential oil on 11 human cancer cell lines. Compared to the essential oil, furanodiene showed stronger growth inhibitions on Hela, Hep-2, HL-60, PC3, SGC-7901 and HT-1080 cells with IC50 between 0.6–4.8 μg/ml. In vivo, furanodiene was also found to exhibit inhibitory effects on the growth of uterine cervical (U14) and sarcoma 180 (Sl80) tumors in mice. Our data suggests that furanodiene, an active component from the essential oil of Wen Ezhu, possesses efficacy against uterine cervical cancer.

Design, Synthesis and In vitro Cytotoxic Evaluation of Novel Hybrids of Artemisinin and Quinazolinone

2021 ◽  
Vol 18 ◽  
Author(s):  
Tran Khac Vu ◽  
Bach Xuan Nguyen ◽  
Linh Nguyen Pham Duy ◽  
Thuc Bao Nguyen Truong ◽  
Anh Tuan Phung ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
Anti Cancer ◽  
Ic50 Values ◽  
Mcf 7

Background: In this study, two novel hybrid series of artemisinin and quinazolinones were synthesized and evaluated in vitro cytotoxicity against two human cancer cell lines, including SKLu-1 (lung cancer), MCF- 7 (breast cancer). The bio-assay results indicated that most of the target compounds exhibited cytotoxic activities against both human cancer cell lines tested, and seemed to be more cytotoxic toward the breast (MCF-7) cancer cells than lung (SKLu-1) cancer cells. Among the synthesized artemisinin hybrids, the compound 13d containing a quinazolinone conjugated system exhibited the most potent cytotoxicity against the SKLu-1 and MCF-7 cell lines with IC50 values of 1.62 and 0.77 µM, respectively. Objective: This study aims at developing novel hybrids of artemisinin and quinazolinones as anti-cancer agents. Method: A series of novel hybrids were designed, synthesized and evaluated for cytotoxicity against two human cancer cell lines, including SKLu-1 and MCF-7 using SRB method. Results : All thirteen hybrids of artemisinin with quinazolinone exhibited cytotoxic activity against two tested cancer cell lines, in which the compound 13d exhibited the most potent cytotoxicity against the SKLu-1 and MCF-7 cell lines with IC50 values of 1.62 and 0.77 µM, respectively. Conclusion: The research results suggest that some compounds could be considered as leads for future design of hybrids and have the potential for further studies in the field of anti-cancer agent development.

scholarly journals Biological evaluation of tubulysin A: a potential anticancer and antiangiogenic natural product

2006 ◽  
Vol 396 (2) ◽  
pp. 235-242 ◽  
Author(s):  
Gurmeet Kaur ◽  
Melinda Hollingshead ◽  
Susan Holbeck ◽  
Vesna Schauer-Vukašinović ◽  
Richard F. Camalier ◽  
...  
Keyword(s):  
Natural Product ◽  
Cell Lines ◽  
Animal Studies ◽  
Human Cancer ◽  
Biological Evaluation ◽  
Hollow Fibre ◽  
In Vitro Assays ◽  
Human Cancer Cell Lines ◽  
Anticancer Properties

Tubulysin A (tubA) is a natural product isolated from a strain of myxobacteria that has been shown to depolymerize microtubules and induce mitotic arrest. The potential of tubA as an anticancer and antiangiogenic agent is explored in the present study. tubA shows potent antiproliferative activity in a panel of human cancer cell lines irrespective of their multidrug resistance properties. It induces apoptosis in cancer cells but not in normal cells and shows significant potential antiangiogenic properties in several in vitro assays. It is efficacious in initial animal studies using a hollow fibre assay with 12 different human tumour cell lines. This study suggests that both in vitro and preclinical profiles of tubA may translate into clinically useful anticancer properties.

scholarly journals Pharmacological Effects of Grifolin: Focusing on Anticancer Mechanisms

Molecules ◽  
2022 ◽  
Vol 27 (1) ◽  
pp. 284
Author(s):  
Abdelhakim Bouyahya ◽  
Aicha El Allam ◽  
Ikrame Zeouk ◽  
Douae Taha ◽  
Gokhan Zengin ◽  
...  
Keyword(s):  
Human Cancer ◽  
Human Cancer Cell Lines ◽  
Beneficial Effects ◽  
Human Cancer Cells ◽  
Pharmaceutical Application ◽  
Cycle Arrest ◽  
Ability To Act ◽  
Anti Cancer

Grifolin is a volatile compound contained in essential oils of several medicinal plants. Several studies show that this substance has been the subject of numerous pharmacological investigations, which have yielded interesting results. Grifolin demonstrated beneficial effects for health via its multiple pharmacological activities. It has anti-microbial properties against bacteria, fungi, and parasites. In addition, grifolin exhibited remarkable anti-cancer effects on different human cancer cells. The anticancer action of this molecule is related to its ability to act at cellular and molecular levels on different checkpoints controlling the signaling pathways of human cancer cell lines. Grifolin can induce apoptosis, cell cycle arrest, autophagy, and senescence in these cells. Despite its major pharmacological properties, grifolin has only been investigated in vitro and in vivo. Therefore, further investigations concerning pharmacodynamic and pharmacokinetic tests are required for any possible pharmaceutical application of this substance. Moreover, toxicological tests and other investigations involving humans as a study model are required to validate the safety and clinical applications of grifolin.

Sign in / Sign up

Export Citation Format

Share Document