scholarly journals Differential Cytotoxic Potential of Acridocarpus orientalis Leaf and Stem Extracts with the Ability to Induce Multiple Cell Death Pathways

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3976 ◽  
Author(s):  
Sameera Omar Mohammed Saeed Balhamar ◽  
Neena Gopinathan Panicker ◽  
Shaima Akhlaq ◽  
Mohammed Mansoor Qureshi ◽  
Waqar Ahmad ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Hela Cells ◽  
Proliferative Potential ◽  
Normal Cells ◽  
Cell Death Pathways ◽  
Methanolic Extracts ◽  
Cervical Cancer Cells ◽  
Multiple Cell ◽  
Apoptotic Pathways

This study systematically analyzed the anticancer potential of Acridocarpus orientalis (AO), a traditional medicinal plant of the Arabian Peninsula/East Africa known for its anti-inflammatory and pain relief properties. Tests of serial organic fractions from methanolic extracts of its leaves and stems revealed that only some fractions showed anti-proliferative potential with the dichloromethane fraction from leaves (AOD (L)) showing the most cytotoxic effect against both breast (MCF-7 and MDA-MB-231) and cervical (HeLa) cancer cell lines. The n-butanol fraction from the stems (AOB (S)), on the other hand, was more effective against cervical cancer cells and did not harm the normal cells. Further characterization of the mode of cell killing revealed that AOD (L) depended more on non-apoptotic pathways for its cytotoxicity in breast cancer cells, while it could activate some apoptosis and necroptosis in HeLa cells. The AOB (S) fraction could primarily activate apoptosis and some necroptosis in HeLa cells. Both fractions perturbed autophagy, but in a dissimilar manner. Thus, different parts of A. orientalis revealed variable potential to induce cell death in cancer cells via apoptotic and non-apoptotic pathways, making A. orientalis a valuable plant for the exploration of anticancer bioactive reagents, some of which may be protective for normal cells.

scholarly journals Silymarin and Cancer: A Dual Strategy in Both in Chemoprevention and Chemosensitivity

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2009 ◽  
Author(s):  
Dominique Delmas ◽  
Jianbo Xiao ◽  
Anne Vejux ◽  
Virginie Aires
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Current Knowledge ◽  
Organic Anion ◽  
Chemotherapeutic Agents ◽  
Normal Cells ◽  
Antiapoptotic Proteins ◽  
Cell Death Pathways ◽  
Anion Transporters ◽  
Atp Binding Cassettes

Silymarin extracted from milk thistle consisting of flavonolignan silybin has shown chemopreventive and chemosensitizing activity against various cancers. The present review summarizes the current knowledge on the potential targets of silymarin against various cancers. Silymarin may play on the system of xenobiotics, metabolizing enzymes (phase I and phase II) to protect normal cells against various toxic molecules or to protect against deleterious effects of chemotherapeutic agents on normal cells. Furthermore, silymarin and its main bioactive compounds inhibit organic anion transporters (OAT) and ATP-binding cassettes (ABC) transporters, thus contributing to counteracting potential chemoresistance. Silymarin and its derivatives play a double role, namely, limiting the progression of cancer cells through different phases of the cycle—thus forcing them to evolve towards a process of cell death—and accumulating cancer cells in a phase of the cell cycle—thus making it possible to target a greater number of tumor cells with a specific anticancer agent. Silymarin exerts a chemopreventive effect by inducing intrinsic and extrinsic pathways and reactivating cell death pathways by modulation of the ratio of proapoptotic/antiapoptotic proteins and synergizing with agonists of death domains receptors. In summary, we highlight how silymarin may act as a chemopreventive agent and a chemosensitizer through multiple pathways.

Abstract 1853: The Chk1 inhibitor, SRA737, synergizes with niraparib to kill cancer cells via multiple cell death pathways

2018 ◽  
Author(s):  
Laurence Booth ◽  
Jane Roberts ◽  
Andrew Poklepovic ◽  
Ryan J. Hansen ◽  
Bryan Strouse ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Cell Death Pathways ◽  
Multiple Cell ◽  
Chk1 Inhibitor

scholarly journals Many si/shRNAs can kill cancer cells by targeting multiple survival genes through an off-target mechanism

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
William Putzbach ◽  
Quan Q Gao ◽  
Monal Patel ◽  
Stijn van Dongen ◽  
Ashley Haluck-Kangas ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Cellular Mirnas ◽  
Unrelated Control ◽  
Reading Frame ◽  
Cell Death Pathways ◽  
Survival Gene ◽  
Simultaneous Activation ◽  
Multiple Cell ◽  
Target Effect

Over 80% of multiple-tested siRNAs and shRNAs targeting CD95 or CD95 ligand (CD95L) induce a form of cell death characterized by simultaneous activation of multiple cell death pathways preferentially killing transformed and cancer stem cells. We now show these si/shRNAs kill cancer cells through canonical RNAi by targeting the 3’UTR of critical survival genes in a unique form of off-target effect we call DISE (death induced by survival gene elimination). Drosha and Dicer-deficient cells, devoid of most miRNAs, are hypersensitive to DISE, suggesting cellular miRNAs protect cells from this form of cell death. By testing 4666 shRNAs derived from the CD95 and CD95L mRNA sequences and an unrelated control gene, Venus, we have identified many toxic sequences - most of them located in the open reading frame of CD95L. We propose that specific toxic RNAi-active sequences present in the genome can kill cancer cells.

scholarly journals Assessment of Cytotoxic Activity of Rosemary (Rosmarinus officinalisL.), Turmeric (Curcuma longaL.), and Ginger (Zingiber officinaleR.) Essential Oils in Cervical Cancer Cells (HeLa)

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
P. A. S. R. Santos ◽  
G. B. Avanço ◽  
S. B. Nerilo ◽  
R. I. A. Marcelino ◽  
V. Janeiro ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Death ◽  
Essential Oils ◽  
Cytotoxic Activity ◽  
Cancer Cells ◽  
Hela Cells ◽  
Membrane Integrity ◽  
Annexin V ◽  
Cervical Cancer Cells

The objective of this study was to evaluate the cytotoxic activity of rosemary (REO,Rosmarinus officinalisL.), turmeric (CEO,Curcuma longaL.), and ginger (GEO,Zingiber officinaleR.) essential oils in HeLa cells. Cytotoxicity tests were performedin vitro, using tetrazolium (MTT) and neutral red assays for evaluation of antiproliferative activity by different mechanisms, trypan blue assay to assess cell viability and evaluation of cell morphology for Giemsa to observe the cell damage, and Annexin V to evaluate cell death by apoptosis. CEO and GEO exhibited potent cytotoxic activity against HeLa cells. IC50obtained was 36.6 μg/mL for CEO and 129.9 μg/mL for GEO. The morphology of HeLa cells showed condensation of chromatin, loss of cell membrane integrity with protrusions (blebs), and cell content leakage for cells treated with CEO and GEO, from the lowest concentrations studied, 32.81 μg/mL of CEO and 32.12 μg/mL of GEO. The Annexin V assay revealed a profile of cell death by apoptosis for both CEO and GEO. The results indicate cytotoxic activityin vitrofor CEO and GEO, suggesting potential use as anticancer agents for cervical cancer cells.

scholarly journals Many si/shRNAs can kill cancer cells by targeting multiple survival genes through an off-target mechanism

2017 ◽  
Author(s):  
William Putzbach ◽  
Quan Q. Gao ◽  
Monal Patel ◽  
Stijn van Dongen ◽  
Ashley Haluck-Kangas ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Cellular Mirnas ◽  
Unrelated Control ◽  
Reading Frame ◽  
Cell Death Pathways ◽  
Survival Gene ◽  
Simultaneous Activation ◽  
Multiple Cell ◽  
Target Effect

AbstractOver 80% of multiple tested siRNAs and shRNAs targeting CD95 or CD95 ligand (CD95L) induce a form of cell death characterized by simultaneous activation of multiple cell death pathways preferentially killing transformed and cancer stem cells. We now show these si/shRNAs kill cancer cells through canonical RNAi by targeting the 3’UTR of critical survival genes in a unique form of off-target effect we call DISE (death induced by survival gene elimination). Drosha and Dicer deficient cells, devoid of most miRNAs, are hypersensitive to DISE, suggesting cellular miRNAs protect cells from this form of cell death. By testing 4666 shRNAs derived from the CD95 and CD95L mRNA sequences and an unrelated control gene, Venus, we have identified many toxic sequences - most of them located in the open reading frame of CD95L. We propose that using specific toxic RNAi-active sequences present in the genome can kill cancer cells.

scholarly journals A Priori Activation of Apoptosis Pathways of Tumor (AAAPT) technology: Development of targeted apoptosis initiators for cancer treatment

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0225869
Author(s):  
Raghu S. Pandurangi ◽  
Marco Tomasetti ◽  
Sekar T. Verapazham ◽  
Ramasamy Paulmurugan ◽  
Cynthia Ma ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Tumor Regression ◽  
A Priori ◽  
Specific Cell ◽  
Normal Cells ◽  
Cell Death Pathways ◽  
Survival Pathways ◽  
Apoptosis Pathways

Cancer cells develop tactics to circumvent the interventions by desensitizing themselves to interventions. Amongst many, the principle routes of desensitization include a) activation of survival pathways (e.g. NF-kB, PARP) and b) downregulation of cell death pathways (e.g. CD95/CD95L). As a result, it requires high therapeutic dose to achieve tumor regression which, in turn damages normal cells through the collateral effects. Methods are needed to sensitize the low and non-responsive resistant tumor cells including cancer stem cells (CSCs) in order to evoke a better response from the current treatments. Current treatments including chemotherapy can induce cell death only in bulk cancer cells sparing CSCs and cancer resistant cells (CRCs) which are shown to be responsible for high recurrence of disease and low patient survival. Here, we report several novel tumor targeted sensitizers derived from the natural Vitamin E analogue (AMP-001-003). The drug design is based on a novel concept “A priori activation of apoptosis pathways of tumor technology (AAAPT) which is designed to activate specific cell death pathways and inhibit survival pathways simultaneously and selectively in cancer cells sparing normal cells. Our results indicate that AMP-001-003 sensitize various types of cancer cells including MDA-MB-231 (triple negative breast cancer), PC3 (prostate cancer) and A543 (lung cancer) cells resulting in reducing the IC-50 of doxorubicin in vitro when used as a combination. At higher doses, AMP-001 acts as an anti-tumor agent on its own. The synergy between AMP-001 and doxorubicin could pave a new pathway to use AAAPT leading molecules as neoadjuvant to chemotherapy to achieve better efficacy and reduced off-target toxicity compared to the current treatments.

scholarly journals Effectiveness of Pleurotus ostreatus Extract Through Cytotoxic Test and Apoptosis Mechanism of Cervical Cancer Cells

2017 ◽  
Vol 9 (1) ◽  
pp. 148
Author(s):  
Nuraeni Ekowati ◽  
Aris Mumpuni ◽  
Juni Safitri Muljowati
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cell Death ◽  
Hela Cell ◽  
Cancer Cells ◽  
Bioactive Compounds ◽  
Hela Cells ◽  
Pleurotus Ostreatus ◽  
Proliferation Kinetics ◽  
Cervical Cancer Cells

<p><em>Pleurotus ostreatus</em> is a common mushroom cultivated in Indonesia, and potential properties of bioactive compounds for medicinal mushroom. This study was aimed at obtaining <em>P.ostreatus</em> extract bioactive compounds potential in inhibiting the proliferation of cervical cancer cells (HeLa) and evaluating the HeLa cell proliferation kinetics and HeLa cell death mechanisms. The research was beneficial in making this product can be easily applied in a more controlled industrial scale. Anticancer activity test through a cytotoxic test using the MTT [3- (4,5-dimetiltiazol-2-yl) -2.5-diphenyl tertrazolium bromide], the kinetics proliferation of HeLa cells and HeLa cell death mechanism was performed. Linear regression analysis was used to analyze the data. Ethyl acetate extract of <em>P.</em> <em>ostreatus</em> isolated from Madiun showed the best results with IC <sub>50</sub> = 107.59 µg / ml. HeLa cell proliferation kinetics analysis showed that the application of bioactive compounds 100 µg / ml resulted in an increase of in death of HeLa cells along with length of incubation time. An important finding was that HeLa cells death by apoptosis was greater than by necrosis.  In conclusion, the extracts of <em>P.</em> <em>ostreatus</em>  has the potential to inhibit the growth of HeLa cells.</p><p> </p>

The Antitumor Efficiency of Zinc Finger Nuclease Combined with Cisplatin and Trichostatin A in Cervical Cancer Cells

2020 ◽  
Vol 20 (17) ◽  
pp. 2125-2135
Author(s):  
Ci Ren ◽  
Chun Gao ◽  
Xiaomin Li ◽  
Jinfeng Xiong ◽  
Hui Shen ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Zinc Finger ◽  
Hela Cells ◽  
Colony Formation ◽  
Trichostatin A ◽  
Combined Therapy ◽  
Hpv E7 ◽  
Anti Cancer ◽  
Cervical Cancer Cells

Background: Persistent infection with the high-risk of human papillomavirus (HR-HPVs) is the primary etiological factor of cervical cancer; HR-HPVs express oncoproteins E6 and E7, both of which play key roles in the progression of cervical carcinogenesis. Zinc Finger Nucleases (ZFNs) targeting HPV E7 induce specific shear of the E7 gene, weakening the malignant biological effects, hence showing great potential for clinical transformation. Objective: Our aim was to develop a new comprehensive therapy for better clinical application of ZFNs. We here explored the anti-cancer efficiency of HPV targeted ZFNs combined with a platinum-based antineoplastic drug Cisplatin (DDP) and an HDAC inhibitor Trichostatin A (TSA). Methods: SiHa and HeLa cells were exposed to different concentrations of DDP and TSA; the appropriate concentrations for the following experiments were screened according to cell apoptosis. Then cells were grouped for combined or separate treatments; apoptosis, cell viability and proliferation ability were measured by flow cytometry detection, CCK-8 assays and colony formation assays. The xenograft experiments were also performed to determine the anti-cancer effects of the combined therapy. In addition, the HPV E7 and RB1 expressions were measured by western blot analysis. Results: Results showed that the combined therapy induced about two times more apoptosis than that of ZFNs alone in SiHa and HeLa cells, and much more inhibition of cell viability than either of the separate treatment. The colony formation ability was inhibited more than 80% by the co-treatment, the protein expression of HPV16/18E7 was down regulated and that of RB1 was elevated. In addition, the xenografts experiment showed a synergistic effect between DDP and TSA together with ZFNs. Conclusion: Our results demonstrated that ZFNs combined with DDP or TSA functioned effectively in cervical cancer cells, and it provided novel ideas for the prevention and treatment of HPV-related cervical malignancies.

Targeting multiple cell death pathways extends the shelf life and preserves the function of human and mouse neutrophils for transfusion

2021 ◽  
Vol 13 (604) ◽  
pp. eabb1069
Author(s):  
Yuping Fan ◽  
Yan Teng ◽  
Fabien Loison ◽  
Aiming Pang ◽  
Anongnard Kasorn ◽  
...  
Keyword(s):  
Cell Death ◽  
Shelf Life ◽  
Ex Vivo ◽  
Combined Treatment ◽  
Bacterial Killing ◽  
Immunodeficient Mice ◽  
Cell Death Pathways ◽  
Multiple Cell ◽  
Human And Mouse

Clinical outcomes from granulocyte transfusion (GTX) are disadvantaged by the short shelf life and compromised function of donor neutrophils. Spontaneous neutrophil death is heterogeneous and mediated by multiple pathways. Leveraging mechanistic knowledge and pharmacological screening, we identified a combined treatment, caspases–lysosomal membrane permeabilization–oxidant–necroptosis inhibition plus granulocyte colony-stimulating factor (CLON-G), which altered neutrophil fate by simultaneously targeting multiple cell death pathways. CLON-G prolonged human and mouse neutrophil half-life in vitro from less than 1 day to greater than 5 days. CLON-G–treated aged neutrophils had equivalent morphology and function to fresh neutrophils, with no impairment to critical effector functions including phagocytosis, bacterial killing, chemotaxis, and reactive oxygen species production. Transfusion with stored CLON-G–treated 3-day-old neutrophils enhanced host defenses, alleviated infection-induced tissue damage, and prolonged survival as effectively as transfusion with fresh neutrophils in a clinically relevant murine GTX model of neutropenia-related bacterial pneumonia and systemic candidiasis. Last, CLON-G treatment prolonged the shelf life and preserved the function of apheresis-collected human GTX products both ex vivo and in vivo in immunodeficient mice. Thus, CLON-G treatment represents an effective and applicable clinical procedure for the storage and application of neutrophils in transfusion medicine, providing a therapeutic strategy for improving GTX efficacy.

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