Essential oil of Foeniculum vulgare subsp. piperitum fruits exerts an anti‑tumor effect in triple‑negative breast cancer cells

2022

At present, the growing spread of tumor cases worldwide renders the research of new promising and selective anticancer drugs urgent. The biological action of extracts of medicinal plants or their essential oils (EOs) is an emerging field of interest, since they could comprise a rich source of phytochemicals that can prove promising. In the present study, the biological activity and mechanism of action of the EO of Foeniculum vulgare subsp. piperitum fruits (FVPEO) were investigated using MTT assays, morphological analyses and western blotting in MDA‑MB231 cells, a triple‑negative breast cancer cell line. The findings revealed that FVPEO could exert strong anticancer effects, causing a dose‑…

A Deadly Liaison between Oxidative Injury and p53 Drives Methyl-Gallate-Induced Autophagy and Apoptosis in HCT116 Colon Cancer Cells

2023

Methyl gallate (MG), which is a gallotannin widely found in plants, is a polyphenol used in traditional Chinese phytotherapy to alleviate several cancer symptoms. Our studies provided evidence that MG is capable of reducing the viability of HCT116 colon cancer cells, while it was found to be ineffective on differentiated Caco-2 cells, which is a model of polarized colon cells. In the first phase of treatment, MG promoted both early ROS generation and endoplasmic reticulum (ER) stress, sustained by elevated PERK, Grp78 and CHOP expression levels, as well as an upregulation in intracellular calcium content. Such events were accompanied by an autophagic process (16–24 h), where prolonging the …

The effect of 3-aminobenzamide, inhibitor of poly(ADP-ribose) polymerase, on human osteosarcoma cells

2003

This study demonstrates that in human osteosarcoma cells treatment with 3-aminobenzamide (3-AB), a potent inhibitor of poly(ADP-ribose) polymerase (PARP), induces morphological and biochemical features of differentiation, the duration of which depends on whether or not the normal RB gene is expressed. In Saos-2 cells expressing a non-functional Rb protein, 3-AB treatment induced the formation of transient, short dendritic-like protrusions. In RB-transfected-Saos-2 cells (a clone previously generated in our laboratory that shows stable expression of wild-type Rb protein), 3-AB induced marked and prolonged changes with the formation of long dendritic-like protrusions and the appearance of ste…

pRb suppresses camptothecin-induced apoptosis in human osteosarcoma Saos-2 cells by inhibiting c-Jun N-terminal kinase

2001

AbstractThis paper studies the cytotoxic effect induced by the topoisomerase I inhibitor camptothecin in human osteosarcoma Saos-2 cells, which lack p53 and contain a non-functional form of the product of the retinoblastoma gene, pRb. Cytotoxicity induced by camptothecin was dose- and time-dependent; the treatment with 100 nM camptothecin reduced cell viability by 50% at 32 h and by 75% at 72 h of exposure. The cytotoxic effect was caused by apoptosis, as ascertained by morphological evidence, acridine orange-ethidium bromide staining and flow cytometric analysis. Apoptosis was accompanied by both the activation of caspase-3 and the fragmentation of poly(ADP-ribose) polymerase. Treatment wi…

The Synergistic Effect of SAHA and Parthenolide in MDA-MB231 Breast Cancer Cells

2015

The sesquiterpene lactone Parthenolide (PN) exerted a cytotoxic effect on MDA-MB231 cells, a triple-negative breast cancer (TNBC) cell line, but its effectiveness was scarce when employed at low doses. This represents an obstacle for a therapeutic utilization of PN. In order to overcome this difficulty we associated to PN the suberoylanilide hydroxamic acid (SAHA), an histone deacetylase inhibitor. Our results show that SAHA synergistically sensitized MDA-MB231 cells to the cytotoxic effect of PN. It is noteworthy that treatment with PN alone stimulated the survival pathway Akt/mTOR and the consequent nuclear translocation of Nrf2, while treatment with SAHA alone induced autophagic activity…

Differentiative pathway activated by 3-aminobenzamide, an inhibitor of PARP, in human osteosarcoma MG-63 cells

2004

AbstractThis study describes the molecular mechanism by which treatment with 3-AB, a potent inhibitor of PARP, allows human osteosarcoma MG-63 cells to restrict growth and enter differentiation. Our findings show that in MG-63 cells, aberrant gene expression keeps Rb protein constitutively inactivated through hyperphosphorylation and this promotes uncontrolled proliferation of the cells. After 3-AB-treatment, the poly(ADP-ribosyl)ation of nuclear proteins markedly decreases and this results in an increase in both the hypophosphorylated active form of Rb and pRb/E2F complexes. These effects are accompanied by G1 arrest, downregulation of gene products required for proliferation (cyclin D1, β…

Apoptosis induced by the histone deacetylase inhibitor SAHA in human colon adenocarcinoma cell line HT29

2006

ER+-derived breast cancer stem cells reveal a high expression of the serpin protease inhibitor PI-9.

2015

Introduction: Breast cancers (BC) are the major cause of death in women. More than 70% of BCs express high levels of estrogen receptor-α (ERα) and are sustained for their growth by the hormone. Estrogens seem to protect BC cells from apoptosis mediated by immunosurveillance associated with cytotoxic T lymphocytes and NK cells granzyme B release. However, the production of granzyme B inhibitor PI-9 by tumor cells causes a short-circuit in immunosurveillance’s signalling. Although it has been shown the role of PI-9 in BC cells, its presence has not been investigated in tumor stem cells so far. Methods: Cell viability was evaluated by MTT, cell cycle by propidium iodide staining; mRNA and prot…

RB1 in cancer: Different mechanisms of RB1 inactivation and alterations of pRb pathway in tumorigenesis

2013

Loss of RB1 gene is considered either a causal or an accelerating event in retinoblastoma. A variety of mechanisms inactivates RB1 gene, including intragenic mutations, loss of expression by methylation and chromosomal deletions, with effects which are species-and cell type-specific. RB1 deletion can even lead to aneuploidy thus greatly increasing cancer risk. The RB1gene is part of a larger gene family that includes RBL1 and RBL2, each of the three encoding structurally related proteins indicated as pRb, p107, and p130, respectively. The great interest in these genes and proteins springs from their ability to slow down neoplastic growth. pRb can associate with various proteins by which it …

Polymerase Chain Reaction (PCR)

2008

The Good and Bad of Nrf2: An Update in Cancer and New Perspectives in COVID-19

2021

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a well-known transcription factor best recognised as one of the main regulators of the oxidative stress response. Beyond playing a crucial role in cell defence by transactivating cytoprotective genes encoding antioxidant and detoxifying enzymes, Nrf2 is also implicated in a wide network regulating anti-inflammatory response and metabolic reprogramming. Such a broad spectrum of actions renders the factor a key regulator of cell fate and a strategic player in the control of cell transformation and response to viral infections. The Nrf2 protective roles in normal cells account for its anti-tumour and anti-viral functions. However, Nrf2 over…

Immuno-Fluorescence (IF) on interphase polytene chromosomes of Drosophila melanogaster

2008

The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis

2020

Combining phytochemicals with chemotherapics is an emerging strategy to treat cancer to overcome drug toxicity and resistance with natural compounds. We assessed the effects of indicaxanthin (Ind), a pigment obtained from Opuntia ficus-indica (L. Mill) fruit, combined with cisplatin (CDDP) against cervical cancer cells (HeLa). Measured cell viability via Trypan blue assay

Multifaceted Health Benefits of Mangifera indica L. (Mango): The Inestimable Value of Orchards Recently Planted in Sicilian Rural Areas

2017

Historically, Mangifera indica L. cultivations have been widely planted in tropical areas of India, Africa, Asia, and Central America. However, at least 20 years ago its spreading allowed the development of some cultivars in Sicily, an island to the south of Italy, where the favourable subtropical climate and adapted soils represent the perfect field to create new sources of production for the Sicilian agricultural supply chain. Currently, cultivations of Kensington Pride, Keitt, Glenn, Maya, and Tommy Atkins varieties are active in Sicily and their products meet the requirements of local and European markets. Mango plants produce fleshy stone fruits rich in phytochemicals with an undispute…

Composizioni farmaceutiche per il trattamento di tumori epatici

2009

Parthenolide induces EGF receptor phosphorylation and superoxide anion production in MDA-MB231 breast cancer cells.

2013

“Acetilazione di p53 e degli istoni nell’apoptosi indotta dal SAHA in cellule di epatoma umano HepG2”

2006

The mechanism by which histone deacetylase inhibitors sensitize hepatoma and colon cancer cells to TRAIL-induced apoptosis

2008

Proteasome inhibitor Velcade induces apoptosis in hepatoma HepG2 cells stimulating both the extrinsic and the intrinsic apoptotic pathways.

2004

Differentiation induced by 3-aminobenzamide in human osteosarcoma MG-63 cells is mediated by the inhibition of the Wnt/β-catenin pathway

2006

JNK and AP-1 mediate apoptosis induced by bortezomib in HepG2 cells via FasL/caspase-8 and mitochondria-dependent pathways

2006

The proteasome inhibitor bortezomib is an efficacious apoptotic agent in many tumor cells. This paper shows that bortezomib induced apoptosis in human hepatoma HepG2 cells associated with many modifications in the expression of survival or death factors. Although bortezomib increased the level of the protective factors HSP70 and HSP27, the effects of the drug that favour cell death were predominant. These events include accumulation of c-Jun, phospho-c-Jun and p53; increase in FasL level with activation of caspase-8; changes related to members of Bcl-2 family with increase in the level of pro-apoptotic members and decrease in that of anti-apoptotic ones; dissipation of mitochondrial potenti…

The sensitization of HepG2 and HT29 cells to TRAIL-induced apoptosis by histone deacetylase inhibitors is mediated by down-regulation of AKT and NF-k…

2008

Differentiation of human osteosarcoma 3AB-OS stem-like cells in derivatives of the three primary germ layers as an useful in vitro model to develop s…

2013

A number of solid tumors contain a distinct subpopulation of cells, termed cancer stem cells (CSCs) which represent the source for tissue renewal and hold malignant potential and which would be responsible for therapy resistance. Today, the winning goal in cancer research would be to find drugs to kill both cancer cells and cancer stem cells, while sparing normal cells. Osteosarcoma is an aggressive pediatric tumor of growing bones that, despite surgery and chemotherapy, is prone to relapse. We have recently selected from human osteosarcoma MG63 cells a cancer stem-like cell line (3AB-OS), which has unlimited proliferative potential, high levels of stemness-related markers, and in vivo tumo…

Parthenolide sensitizes human hepatocarcinoma cells to TRAIL-induced apoptosis

2009

Role of the acetylation of p53 and histones in SAHA-induced apoptosis in human hepatoma HepG2 cells.

2007

Histone deacetylase inhibitors: Epigenetic drugs acting by pleiotropic apoptotic mechanism in tumor cells and highly potent in combination with other…

2007

3AB-OS, a human osteosarcoma stem-like cell line, potential model for studying cancer

2012

Parthenolide induces caspase-independent cell death mediated by AIF in osteosarcoma and melanoma cells.

2012

Parthenolide, the major bioactive sesquiterpene lactone present in Feverfew (Tanacetum parthenium), has recently attracted considerable attention because of its complex pharmacological action involving anti-microbial, anti-inflammatory and anti-cancer effects. However, the mechanism of its cytotoxic effect on tumor cells still remains scarcely defined today. The aim of this study was to analyse the mechanism of parthenolide action on two lines of cancer cells, the human osteosarcoma MG63 and the melanoma SK-MEL-28 cells, on which parthenolide exerted its action inducing similar effects. Staining with Hoechst 33342 showed that parthenolide induced in the first phase of treatment (0-5 h) in m…

THE ROLE OF THE EXTRINSIC PATHWAY OF APOPTOSIS IN THE EFFECT INDUCED BY SAHA IN HUMAN HEPATOMA CELLS.

2006

Parthenolide generates reactive oxygen species and autophagy in MDA-MB231 cells. A soluble parthenolide analogue inhibits tumour growth and metastasi…

2013

Triple-negative breast cancers (TNBCs) are clinically aggressive forms associated with a poor prognosis. We evaluated the cytotoxic effect exerted on triple-negative MDA-MB231 breast cancer cells both by parthenolide and its soluble analogue dimethylamino parthenolide (DMAPT) and explored the underlying molecular mechanism. The drugs induced a dose- and time-dependent decrement in cell viability, which was not prevented by the caspase inhibitor z-VAD-fmk. In particular in the first hours of treatment (1–3 h), parthenolide and DMAPT strongly stimulated reactive oxygen species (ROS) generation. The drugs induced production of superoxide anion by activating NADPH oxidase. ROS generation caused…

Post-translational modifications of hsp60 and its extracellular release via exosomes are induced by the histone deacetylase inhibitor (HDACi) SAHA in…

2015

The chaperonin Hsp60 has multiple functions, among which that of supporting the growth of some type of tumours (1). HDACi (histone-deacetylase inhibitors) are drugs that regulate gene expression via modulation of epigenetic mechanisms, and induce tumor-cell death (2). Here, we show that in the tumor cells H292 the HDACi SAHA decreases the intracellular level of Hps60 and promotes its extracellular trafficking by exosomal vesicles. SAHA caused a time- and dose-dependent decrease in cell viability with a G/2M cell-cycle arrest at 24 h and cell death at 48 h. These effects were accompanied by production of reactive oxygen species and mitochondrial membrane-potential dissipation. The marked dec…

Parthenolide induces caspase-independent and AIF mediated cell death in tumor cells

2012

SYNERGISTIC APOPTOTIC INTERACTION BETWEEN THE HDAC INHIBITOR SAHA AND THE PROTEASOME INHIBITOR BORTEZOMIB IN HUMAN HEPATOMA CELLS.

2005

RB1 in cancer: Different mechanisms of RB1 inactivation and alterations of pRb pathway in tumorigenesis.

2013

Loss of RB1 gene is considered either a causal or an accelerating event in retinoblastoma. A variety of mechanisms inactivates RB1 gene, including intragenic mutations, loss of expression by methylation and chromosomal deletions, with effects which are species-and cell type-specific. RB1 deletion can even lead to aneuploidy thus greatly increasing cancer risk. The RB1gene is part of a larger gene family that includes RBL1 and RBL2, each of the three encoding structurally related proteins indicated as pRb, p107, and p130, respectively. The great interest in these genes and proteins springs from their ability to slow down neoplastic growth. pRb can associate with various proteins by which it …

JNK AND AP-1 MEDIATE APOPTOSIS INDUCED BY BORTEZOMIB IN HEPATOMA HEPG2 CELLS.

2005

Phosphatidylinositol-3-kinase activity during in vitro dendritic cell generation determines suppressive or stimulatory capacity.

2011

Modulating PI3K at different stages of dendritic cells (DC) generation could be a novel means to balance the generation of immunosuppressive versus immunostimulatory DC. We show that PI3K inhibition during mouse DC generation in vitro results in cells that are potently immunosuppressive and characteristic of CD8alpha- CD11c+ CD11b+ DC. These DC exhibited low surface class I and class II MHC, CD40, and CD86 and did not produce TNF-alpha. In allogeneic MLR, these DC were suppressive. Although in these mixed cultures, there was no increase in the frequency of CD4+ CD25+ Foxp3+ cells, the Foxp3 content on a per cell basis was significantly increased. Sustained TLR9 signaling in the presence of …

The synergistic effect of SAHA and parthenolide in MDA-MB231 breast cancer cells

2014

Abstract: The sesquiterpene lactone Parthenolide (PN) exerted a cytotoxic effect on MDA-MB231 cells, a triple-negative breast cancer (TNBC) cell line, but its effectiveness was scarce when employed at low doses. This represents an obstacle for a therapeutic utilization of PN. In order to overcome this difficulty we associated to PN the suberoylanilide hydroxamic acid (SAHA), an histone deacetylase inhibitor. Our results show that SAHA synergistically sensitized MDA-MB231 cells to the cytotoxic effect of PN. It is noteworthy that treatment with PN alone stimulated the survival pathway Akt/mTOR and the consequent nuclear translocation of Nrf2, while treatment with SAHA alone induced autophagi…

Evaluation of the in vitro and in vivo antineoplastic effects of Parthenolide on MDA-MB231 breast cancer cells

2012

Triple-negative breast cancer refers to an aggressive subtype of breast cancer in which the tumor cells lack receptors for estrogen, progesterone and the HER2 protein on their surfaces. This type of breast cancer does not respond to treatments such as hormone therapy, like tamoxifen and aromatase inhibitors, or drugs that target HER2, like Herceptin. It is important, therefore, the identification of new selective drugs for the treatment of these tumors. Parthenolide (PN), a sesquiterpene lactone extracted from the medical plant Tanacetum parthenium, exerts anticancer activity on several tumor cell lines in culture, acting through diverse molecular mechanisms. Our previous studies have shown…

Oxidative stress induced by the novel compound tributyltin(iv) ferulate promotes ER stress and autophagy in colon cancer cells

2021

Differentiative pathway induced by 3-aminobenzamide in MG-63 human osteosarcoma cells.

2004

ATTIVITÀ ANTIPROLIFERATIVA DI UN DERIVATO POLICICLICO CON STRUTTURA COMPLESSA

2014

Un nuovo derivato policiclico glicosilato è stato ottenuto partendo dal derivato policiclico iodurato, utilizzando la reazione di Sonogashira.Il composto glicosilato saggiato presso l’NCI è risultato attivo su tutte le 60 linee cellulari tumorali del panel, risultando più attivo degli altri composti policiclici precedentemente saggiati. Il composto induce l’arresto del ciclo cellulare in fase G2/M nella linea cellulare MDA-MB231, fa diminuire i livelli di ciclina B1e Cdc-2 mentre produce un aumento dell’inibitore p21WAF1, una chinasi ciclino-dipendente.

Multimodal Strategies to Fight Obesity: Research on Tailored Therapies Based on Natural and Synthetic Compounds for Prevention, Management and Treatm…

2023

Synergistic cytotoxic interaction of the HDAC inhibitor SAHA with the natural compound parthenolide in MDA-MB231 breast cancer cells.

2013

THE APOPTOTIC EFFECT INDUCED IN HepG2 CELLS BY INHIBITORS OF HISTONE DEACETYLASES IS CORRELATED WITH ACETYLATION OF p53 AND HISTONES.

2007

Synergistic effect of the HDAC inhibitor SAHA and the sesquiterpene lactone parthenolide in triple negative breast cancer cells.

2014

Il partenolide stimola la produzione di ROS e autofagia in cellule di carcinoma mammario MDA-MB231.Il suo analogo solubile DMAPT inibisce la crescita…

2013

Synergistic interaction between Parthenolide and TRAIL induces apoptosis in human hepatocarcinoma cells.

2009

Partenolide, a natural compound used in traditional medicine for its anti-inflammatory activity, has recently shown anti-tumor and apoptotic effects. Our studies demonstrated that HepG2; Hep3B and SK-Hep1 hepatocarcinoma cells, which are resistant to human recombinant TRAIL, are potently sensitized to TRAIL-induced apoptosis by low doses of parthenolide resulting in a marked synergist effect. To clarify the mechanism that accounts for this interaction, we demonstrated that parthenolide/TRAIL combination markedly increased DR4 and DR5. These effects might be correlated with STAT proteins modifications. In fact parthenolide and parthenolide/TRAIL combination decreased STAT3 and STAT5 and thei…

“Effects of histone deacetylase inhibitors in human hepatoma cells and synergistic apoptotic interaction with the proteasome inhibitor Bortezomib”

2006

Parthenolide induces caspase-independent cell death in osteosarcoma, melanoma and breast cancer cells through the induction of oxidative stress.

2012

Parthenolide, a sesquiterpene lactone found in European feverfew, is used in traditional medicine for its anti-inflammatory activity. In addition, parthenolide has been considered as a novel and effective anti-tumor agent because it induces cytotoxic effects in several tumor cell lines. Our studies demonstrated that parthenolide exerted strong cytotoxic effects in osteosarcoma MG63 and melanoma SK-Mel28 cells in culture. Staining with Hoechst 33342 revealed in most cells after brief periods of treatments (3-5h) chromatin condensation and fragmentation, while only few cells were PI-positive. Prolonging the treatment (5-14h) PI-positive cells strongly augmented, denouncing the increase of nec…

Anti tumor action of the natural compound parthenolide

2010

THE APOPTOTIC EFFECT EXERTED IN HUMAN HEPATOMA CELLS BY THE INHIBITOR OF HISTONE DEACETYLASE SAHA EITHER ALONE OR IN COMBINATION WITH BORTEZOMIB.

2005

Interleukin-7 matures suppressive CD127(+) forkhead box P3 (FoxP3)(+) T cells into CD127(-) CD25(high) FoxP3(+) regulatory T cells.

2011

We have identified a novel interleukin (IL)-7-responsive T cell population [forkhead box P3 (FoxP3(+) ) CD4(+) CD25(+) CD127(+) ] that is comparably functionally suppressive to conventional FoxP3(+) CD4(+) CD25(+) regulatory T cells (T(regs) ). Although IL-2 is the most critical cytokine for thymic development of FoxP3(+) T(regs) , in the periphery other cytokines can be compensatory. CD25(+) CD127(+) T cells treated with IL-7 phenotypically 'matured' into the known 'classical' FoxP3(+) CD4(+) CD25(high) CD127(-) FoxP3(+) T(regs) . In freshly isolated splenocytes, the highest level of FoxP3 expression was found in CD127(+) CD25(+) T cells when compared with CD127(-) CD25(+) or CD127(+) CD25…

WIN-induced vesiculation cooperates to the inhibition of osteosarcoma cell migration

2015

Introduction. Animal cells release vesicles that mediate the secretion of a variety of factors in the surrounding environment affecting neighboring cells. There is increasing evidence that secreted vesicles play an important role as vehicle of intercellular communication in different biological systems and are able to influence both physiological and pathological processes. Recently, we have reported that the synthetic cannabinoid WIN55,512 is able to induce osteosarcoma MG63 cell death and negatively affect cell migration. Here, we study the effects of WIN on the induction of vesicle secretion and their possible role in WIN-dependent reduction of osteosarcoma cell migratory ability. Method…

Effetti benefici degli oli essenziali nel trattamento anti-obesità

2023

The involvement of the c-Jun/JNK/AP-1 pathway and HSPs in apoptosis induced by the proteasome inhibitor PS-341 (Velcade) in human hepatoma cells.

2004

Karyotypic Complexity and Chromosomal Aberrations In Human Embryonic Cancer Stem Cells 3AB-OS.

2009

The mechanism of parthenolide-induced cell death in tumor cell lines.

2011

Sodium butyrate induces apoptosis in human hepatoma cells by a mitochondria/caspase pathway, associated with degradation of beta-catenin, pRb and Bcl…

2004

Butyrate can promote programmed cell death in a number of tumour cells in vitro. This paper provides evidence that butyrate induces apoptosis in human hepatoma HuH-6 and HepG2 cells but is ineffective in Chang liver cells, an immortalised non-tumour cell line. In both HuH-6 and HepG2 cells, apoptosis appeared after a lag period of approximately 16 h and increased rapidly during the second day of treatment. In particular, the effect was stronger in HuH-6 cells, which were, therefore, chosen for ascertaining the mechanism of butyrate action. In HuH-6 cells, beta-catenin seemed to exert an important protective role against apoptosis, since pretreatment with beta-catenin antisense ODN reduced t…

Possible regulatory mechanisms responsible for the high expression of serpin protease inhibitor PI-9 in ER+ -derived breast cancer stem cells.

2015

Breast cancer (BC) is the most common endocrine cancer and the second leading cause of cancer-related death in women. About 75% of BCs expresses high levels of estrogen receptors that sustain the tumor growth. Moreover, in BC estrogens prevent apoptosis induced by granzyme B released by cytotoxic T lymphocytes and NK cells through the production of the granzyme B inhibitor PI-9. As a consequence, cancer cells acquire the ability to escape immune surveillance’s signaling. Although some studies explored the role of PI-9 in BC cells, its presence has not been investigated in cancer stem cells so far. In this research, tertiary tumorspheres were obtained from estrogen receptor-alfa positive (ER…

HISTONE DEACETYLASE INHIBITORS SENSITIZE HEPATOMA CELLS TO TRAIL_INDUCED APOPTOSIS

2008

The cannabinoid system and its potential therapeutic applications in cancer.

2007

Induction of apoptosis in human osteosarcoma Saos-2 cells by the proteasome inhibitor MG132 and the protective effect of pRb

2003

Induction of apoptosis in human osteosarcoma Saos-2 cells by the proteasome inhibitor MG132 and the protective effect of pRb

Autophagic cell death induced by Litchi fruit extracts in human colon cancer cells.

2016

Litchi chinensis is a tropical fruit which cultivation has been recently introduced in Sicily. Some findings have shown that Litchi extracts display antitumor effects but the underlying mechanisms have not been elucidated. This study focuses on the effects of Litchi hydro-alcoholic extracts in colorectal cancer cells. The results indicated that Litchi exocarp (peel), mesocarp (pulp) and endocarp (seeds) extracts reduce the viability of HT-29 colon cancer cells in a dose dependent manner. This effect was accompanied with G2/M arrest of the cell cycle followed by cell death. Interestingly, exocarp and endocarp extracts triggered an autophagic response in the first phase of treatment (16-24h) …

Il partenolide sensibilizza le cellule di epatocarcinoma all'apoptosi indotta da TRAIL

2009

Il partenolide induce morte in cellule di osteosarcoma umano MG63 mediante un meccanismi caspasi-indipendente, mediato da AIF.

2012

Parthenolide induces superoxide anion production by stimulating EGF receptor in MDA-MB-231 breast cancer cells

2013

The sesquiterpene lactone parthenolide (PN) has recently attracted considerable attention because of its anti-microbial, anti-inflammatory and anticancer effects. However, the mechanism of its cytotoxic action on tumor cells remains scarcely defined. We recently provided evidence that the effect exerted by PN in MDA-MB-231 breast cancer cells was mediated by the production of reactive oxygen species (ROS). The present study shows that PN promoted the phosphorylation of EGF receptor (phospho-EGFR) at Tyr1173, an event which was observed already at 1  h of incubation with 25  µM PN and reached a peak at 8-16  h. This effect seemed to be a consequence of ROS production, because N-acetylcystein…

Okadaic acid-Parthenolide combination at subtoxic doses induces potent synergistic apoptotic effects in human retinoblastoma Y79 cells by upregulatin…

2013

Retinoblastoma is the most common intraocular malignancy afflicting children. The incidence is higher in developing countries, where treatment is limited and long-term survival rates are low. Vincristine, etoposide, and carboplatin -the agents commonly used in the treatment of retinoblastoma- determine side effects causing significant morbidity to pediatric patients and significantly limiting dosing. Thus, identifying new drugs and molecular targets to facilitate the development of novel therapeutics, and finding natural drug combinations to kill cancer cells by synergistically acting at subtoxic doses, may be a good goal. Here, we investigated the effects of two natural compounds, okadaic …

The HDAC inhibitor SAHA synergistically stimulates the cytotoxic effect induced by Parthenolide in MDA-MB231 cells

2014

We showed that the sesquiterpene lactone Parthenolide (PN) exerts strong cytotoxic effects on triple negative breast cancer MDA-MB231 cells. Our recent results suggest that PN exerts in these cells a cytoprotective effect, which is due to the activation of mTOR pathway. To inhibit this protective response we employ the HDAC inhibitor SAHA, which is known to prevent AKT/mTOR pathway. We show that PN activates Akt, mTOR, p70S6kinase and NRF2 while SAHA abolishes these effects. Further cell pretreatment with SAHA synergistically sensitizes the cells to the cytotoxic effect of PN. Moreover SAHA alone activates the autophagic process. The addition of PN to SAHA reduces this effect and induces ap…

SAHA induces apoptosis in hepatoma cells and synergistically interacts with the proteasome inhibitor Bortezomib.

2007

Histone deacetylase (HDAC) inhibitors represent a promising group of anticancer agents. This paper shows that the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) stimulated at 5-10 microM apoptosis in human hepatoma HepG2 and Huh6 cells, but was ineffective in primary human hepatocytes (PHH). In HepG2 cells SAHA induced the extrinsic apoptotic pathway, increasing the expression of both FasL and FasL receptor and causing the activation of caspase-8. Moreover, SAHA enhanced the level of Bim proteins, stimulated alternative splicing of the Bcl-X transcript with the expression of the proapoptotic Bcl-Xs isoform, induced degradation of Bid into the apoptotic factor t-Bid and dephosphorylat…

Derivati policiclici con struttura complessa dotati di attività antiproliferativa

2017

Sono stati sintetizzati composti a struttura policiclica complessa. Tutti i composti sintetizzati sono stati saggiati dall'NCI (USA) su un panel di 60 linee cellulari tumorali umane. Sula base dei risultati ottenuti è stato possibile effettuare uno studio SAR che ha evidenziato come la presenza di gruppi idrofili è necessaria ai fini dell'attività antitumorale. E' stato inoltre studiato il meccanismo d'azione di queste molecole. E' stato notato un arresto delle cellule MDA-MB231 in fase G0/G1 correlato con la defosforilazione ed attivazione, indotta dai composti, della proteina pRb. Il meccanismo comunque varia arrestando il ciclo cellulare in fase G2/M quando per effetto della glicosilazio…

Heat shock protein 60 (Hsp60) modulation by the Histon Deacetylase Inhibitor (HDAC-i) SAHA in mucoepidermoid tumor H292 cells

2014