scholarly journals Harmine Augments the Cytotoxic and Anti-invasive Potential of Temozolomide Against Glioblastoma Multiforme Cells

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Mehran Kamani ◽  
Ali Ghanbari ◽  
Mahdi Taghadosi ◽  
Kamran Mansouri ◽  
Cyrus Jalili
Keyword(s):  
Glioblastoma Multiforme ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Tumor Invasion ◽  
Human Cancer ◽  
Treatment Success ◽  
Invasive Potential ◽  
Dose Reduction Index ◽  
Post Hoc ◽  
Reduction Index

Background: Glioblastoma multiforme (GBM) is considered the deadliest human cancer. Temozolomide is now a part of postresection standard chemotherapy for this type of cancer. Unfortunately, resistance to temozolomide is a major obstacle to treatment success. Combination therapy with natural anticancer agents increases the activity of temozolomide against cancer cells. Objectives: This study aimed to assess the effects of temozolomide in combination with harmine against GBM cells. Methods: Cancer cells were treated with temozolomide and/or harmine. After 24, 48, 72, and 96 h, the viability of the cells was assessed by the MTT test. The combination index and dose reduction index were determined by CompuSyn software. Tumor invasion potential was investigated by evaluating cell migration, invasion, and adhesion. The real-time PCR technique was done to study the expression pattern of two genes involved in cancer cell invasion. Statistical analysis was performed using one-way analysis of variance and Tukey’s post-hoc test, and differences were considered non-significant at P > 0.05. Results: After treatment with temozolomide, cell viability showed a concentration- and time-dependent decrease, and the cells’ survival rate decreased. The combination of temozolomide and harmine had a synergistic effect. Also, temozolomide and/or harmine treatment decreased cancer cells’ migration, invasion, and adhesion potentials, as well as the expression of metalloproteinases 2 and 9 in T98G cells. Conclusions: The combination of temozolomide and harmine can be promising for the successful treatment of GBM.

scholarly journals α-Mangostin Synergizes the Antineoplastic Effects of 5-Fluorouracil Allowing a Significant Dose Reduction in Breast Cancer Cells

Processes ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 458
Author(s):  
Galia Lara-Sotelo ◽  
Lorenza Díaz ◽  
Rocío García-Becerra ◽  
Euclides Avila ◽  
Heriberto Prado-Garcia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Dose Reduction ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
Dependent Manner ◽  
Pharmacological Interaction ◽  
Dose Reduction Index ◽  
Reduction Index

Breast cancer is the most common neoplasm and the leading cause of cancer death in women worldwide. Although 5-fluorouracil is a conventional chemotherapeutic agent for breast cancer treatment, its use may result in severe side effects. Thus, there is widespread interest in lowering 5-fluorouracil drawbacks, without affecting its therapeutic efficacy by the concomitant use with natural products. Herein, we aimed at evaluating whether α-mangostin, a natural antineoplastic compound, could increase the anticancer effect of 5-fluorouracil in different breast cancer cell lines, allowing for dose reduction. Cell proliferation was evaluated by sulforhodamine-B assays, inhibitory concentrations and potency were calculated by dose-response curves, followed by analysis of their pharmacological interaction by the combination-index method and dose-reduction index. Cell cycle distribution was evaluated by flow cytometry. Each compound inhibited cell proliferation in a dose-dependent manner, the triple negative breast cancer cells being the most sensitive. When 5-fluorouracil and α-mangostin were used concomitantly, synergistic antiproliferative effect was observed. The calculated dose-reduction index suggested that this combination exhibits therapeutic potential for reducing 5-fluorouracil dosage in breast cancer. Mechanistically, the cotreatment induced cell death in a greater extent than each drug alone. Therefore, α-mangostin could be used as a potent co-adjuvant for 5-fluorouracil in breast cancer.

scholarly journals Syntheses of l-Rhamnose-Linked Amino Glycerolipids and Their Cytotoxic Activities against Human Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 566
Author(s):  
Makanjuola Ogunsina ◽  
Pranati Samadder ◽  
Temilolu Idowu ◽  
Mark Nachtigal ◽  
Frank Schweizer ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anticancer Agents ◽  
Human Cancer ◽  
Cytotoxic Activities ◽  
Drug Resistant ◽  
Ether Lipids ◽  
Human Cancer Cell Lines ◽  
Human Cancer Cells ◽  
Synthetic Procedure ◽  
Major Impediment

A major impediment to successful cancer treatment is the inability of clinically available drugs to kill drug-resistant cancer cells. We recently identified metabolically stable l-glucosamine-based glycosylated antitumor ether lipids (GAELs) that were cytotoxic to chemotherapy-resistant cancer cells. In the absence of commercially available l-glucosamine, many steps were needed to synthesize the compound and the overall yield was poor. To overcome this limitation, a facile synthetic procedure using commercially available l-sugars including l-rhamnose and l-glucose were developed and the l-GAELs tested for anticancer activity. The most potent analog synthesized, 3-amino-1-O-hexadecyloxy-2R-(O–α-l-rhamnopyranosyl)-sn- glycerol 3, demonstrated a potent antitumor effect against human cancer cell lines derived from breast, prostate, and pancreas. The activity observed was superior to that observed with clinical anticancer agents including cisplatin and chlorambucil. Moreover, like other GAELs, 3 induced cell death by a non-membranolytic caspase-independent pathway.

scholarly journals Antimicrobial Peptides as Anticancer Agents: Functional Properties and Biological Activities

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2850 ◽  
Author(s):  
Anna Lucia Tornesello ◽  
Antonella Borrelli ◽  
Luigi Buonaguro ◽  
Franco Maria Buonaguro ◽  
Maria Lina Tornesello
Keyword(s):  
Antimicrobial Peptides ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Plasma Membranes ◽  
Tumor Antigens ◽  
Human Cancer ◽  
Biological Activities ◽  
Immune Defense ◽  
Anticancer Activities ◽  
Host Defense Peptides

Antimicrobial peptides (AMPs), or host defense peptides, are small cationic or amphipathic molecules produced by prokaryotic and eukaryotic organisms that play a key role in the innate immune defense against viruses, bacteria and fungi. AMPs have either antimicrobial or anticancer activities. Indeed, cationic AMPs are able to disrupt microbial cell membranes by interacting with negatively charged phospholipids. Moreover, several peptides are capable to trigger cytotoxicity of human cancer cells by binding to negatively charged phosphatidylserine moieties which are selectively exposed on the outer surface of cancer cell plasma membranes. In addition, some AMPs, such as LTX-315, have shown to induce release of tumor antigens and potent damage associated molecular patterns by causing alterations in the intracellular organelles of cancer cells. Given the recognized medical need of novel anticancer drugs, AMPs could represent a potential source of effective therapeutic agents, either alone or in combination with other small molecules, in oncology. In this review we summarize and describe the properties and the mode of action of AMPs as well as the strategies to increase their selectivity toward specific cancer cells.

scholarly journals Antitumor effect of Melaleuca alternifolia essential oil and its main component terpinen-4-ol in combination with target therapy in melanoma models

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Marta Di Martile ◽  
Stefania Garzoli ◽  
Manuela Sabatino ◽  
Elisabetta Valentini ◽  
Simona D’Aguanno ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anticancer Agents ◽  
Antitumor Effect ◽  
Human Cancer ◽  
Biological Activities ◽  
Target Therapy ◽  
Human Fibroblasts ◽  
Melaleuca Alternifolia ◽  
Machine Learning Classification ◽  
Main Component

AbstractEssential oils (EOs) have been recently emerging for their promising biological activities in preventing tumorigenesis or progression of different tumor histotypes, including melanoma. In this study, we investigated the antitumor activity of a panel of EOs in different tumor models. The ability of Melaleuca alternifolia (tea tree oil) and its main component, terpinen-4-ol, to sensitize the target therapy currently used for melanoma treatment was also assessed. Our results demonstrated that EOs differently affect the viability of human cancer cells and led us to select six EOs effective in melanoma and lung cancer cells, without toxic effects in human fibroblasts. When combined with dabrafenib and/or trametinib, Melaleuca alternifolia synergistically reduced the viability of melanoma cells by activating apoptosis. Through machine learning classification modeling, α-terpineol, tepinolene, and terpinen-4-ol, three components of Melaleuca alternifolia, were identified as the most likely relevant components responsible for the EO’s antitumor effect. Among them, terpinen-4-ol was recognized as the Melaleuca alternifolia component responsible for its antitumor and proapoptotic activity. Overall, our study holds promise for further analysis of EOs as new anticancer agents and supports the rationale for their use to improve target therapy response in melanoma.

scholarly journals Histamine H1 receptor antagonists selectively kill cisplatin-resistant human cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nobuki Matsumoto ◽  
Miku Ebihara ◽  
Shiori Oishi ◽  
Yuku Fujimoto ◽  
Tomoko Okada ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anticancer Agents ◽  
Human Cancer ◽  
H1 Receptor ◽  
Receptor Antagonists ◽  
Histamine H1 Receptor ◽  
Human Cancer Cells ◽  
Development Of Resistance ◽  
H4 Receptor ◽  
High Level

AbstractCancer therapy is often hampered by the disease’s development of resistance to anticancer drugs. We previously showed that the autonomously upregulated product of fibroblast growth factor 13 gene (FGF13; also known as FGF homologous factor 2 (FHF2)) is responsible for the cisplatin resistance of HeLa cisR cells and that it is likely responsible for the poor prognosis of cervical cancer patients treated with cisplatin. Here we show that cloperastine and two other histamine H1 receptor antagonists selectively kill HeLa cisR cells at concentrations that little affect parental HeLa S cells. The sensitivity of HeLa cisR cells to cloperastine was abolished by knocking down FGF13 expression. Cisplatin-resistant A549 cisR cells were similarly susceptible to cloperastine. H2, H3, and H4 receptor antagonists showed less or no cytotoxicity toward HeLa cisR or A549 cisR cells. These results indicate that histamine H1 receptor antagonists selectively kill cisplatin-resistant human cancer cells and suggest that this effect is exerted through a molecular mechanism involving autocrine histamine activity and high-level expression of FGF13. We think this represents a potential opportunity to utilize H1 receptor antagonists in combination with anticancer agents to treat cancers in which emergent drug-resistance is preventing effective treatment.

Synthesis of New Hydrazone Derivatives and Evaluation of their Efficacy as Proliferation Inhibitors in Human Cancer Cells

2019 ◽  
Vol 15 (8) ◽  
pp. 903-910 ◽  
Author(s):  
Piotr Świątek ◽  
Jolanta Saczko ◽  
Nina Rembiałkowska ◽  
Julita Kulbacka
Keyword(s):  
Cancer Cells ◽  
Anticancer Agents ◽  
Human Cancer ◽  
Anticancer Activities ◽  
Human Cancer Cells ◽  
Viability Assay ◽  
Resistant Phenotype ◽  
Potent Inhibition ◽  
Drug Resistant Phenotype ◽  
Mcf 7

Background: Hydrazine-hydrazones represent a group of bioactive compounds that display antibacterial, anti-inflammatory, antiviral or anticancer activities. Methods: The group of new derivatives was evaluated by the viability assay in human cancer and normal cells. Results: The dimethylpyridine hydrazones showed potent inhibition of cell proliferation of breast, colon cancer cells, human melanoma and glioblastoma. Compound 12 inhibited proliferation of cancer cells exhibiting a drug-resistant phenotype (MCF-7/DX and LoVoDX) at low millimolar concentrations. Whereas, antimelanoma activity was revealed by Compounds 2, 4, 7 and 12. Conclusion: The present results highlighted newly synthetized hydrazine derivatives an excellent base for the design of new anticancer agents and resistance inhibitors.

scholarly journals Implication of Metastasis Suppressor NM23-H1 in Maintaining Adherens Junctions and Limiting the Invasive Potential of Human Cancer Cells

2010 ◽  
Vol 70 (19) ◽  
pp. 7710-7722 ◽  
Author(s):  
Mathieu Boissan ◽  
Olivier De Wever ◽  
Floria Lizarraga ◽  
Dominique Wendum ◽  
Renaud Poincloux ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Adherens Junctions ◽  
Metastasis Suppressor ◽  
Invasive Potential ◽  
Human Cancer Cells

scholarly journals Micelle-in-Liposomes for Sustained Delivery of Anticancer Agents That Promote Potent TRAIL-Induced Cancer Cell Apoptosis

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 157
Author(s):  
Zhenjiang Zhang ◽  
Sagar B. Patel ◽  
Michael R. King
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Water Solubility ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
Cancer Cell Death ◽  
Apoptotic Effect ◽  
New Formulation ◽  
Aqueous Core

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces cancer cell-specific apoptosis and has garnered intense interest as a promising agent for cancer treatment. However, the development of TRAIL has been hampered in part because most human cancer cells are resistant to TRAIL. A few small molecules including natural compounds such as piperlongumine (PL) have been reported to sensitize cancer cells to TRAIL. We prepared a novel type of nanomaterial, micelle-in-liposomes (MILs) for solubilization and delivery of PL. PL-loaded MILs were used to sensitize cancer cells to TRAIL. As visualized by cryo-TEM, micelles were successfully loaded inside the aqueous core of liposomes. The MILs increased the water solubility of PL by ~20 fold. A sustained PL release from MILs in physiologically relevant buffer over 7 days was achieved, indicating that the liposomes prevented premature drug release from the micelles in the MILs. Also demonstrated is a potent synergistic apoptotic effect in cancer cells by PL MILs in conjunction with liposomal TRAIL. MILs provide a new formulation and delivery vehicle for hydrophobic anticancer agents, which can be used alone or in combination with TRAIL to promote cancer cell death.

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