Caspase inhibition blocks apoptosis caused by MLL-AF4 depletion in t(4;11) positive ALL cell lines, but cannot abrogate subsequent necroptosis-like cell death

Introduction:Multiple myeloma (MM) cells accumulate in the bone marrow and produce enormous quantities of immunoglobulins, causing endoplasmatic reticulum stress and activation of protein handling machinery, such as heat shock protein response, autophagy and unfolded protein response (UPR).Methods:We evaluated cell lines viability after treatment with bortezomib (B) in combination with HSP70 (VER-15508) and autophagy (SBI-0206965) or UPR (STF- 083010) inhibitors.Results:For RPMI-8226, after 72 hours of treatment with B+VER+STF or B+VER+SBI, we observed 15% of viable cells, but treatment with B alone was better (90% of cell death). For U266, treatment with B+VER+STF or with B+VER+SBI for 72 hours resulted in 20% of cell viability and both treatments were better than treatment with B alone (40% of cell death). After both triplet combinations, RPMI-8226 and U266 presented the overexpression of XBP-1 UPR protein, suggesting that it is acting as a compensatory mechanism, in an attempt of the cell to handle the otherwise lethal large amount of immunoglobulin overload.Conclusion:Our in vitro results provide additional evidence that combinations of protein homeostasis inhibitors might be explored as treatment options for MM.

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Synthesis, Spectral Characterization, Antibacterial and Anticancer Activity of some Titanium Complexes

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666171219122431 ◽

2018 ◽

Vol 18 (5) ◽

pp. 739-746 ◽

Cited By ~ 2

Author(s):

Raj Kaushal ◽

Nitesh Kumar ◽

Archana Thakur ◽

Kiran Nehra ◽

Pamita Awasthi ◽

...

Keyword(s):

Cell Cycle ◽

Cell Death ◽

Anticancer Activity ◽

Cell Lines ◽

Spectral Characterization ◽

Mechanistic Study ◽

Titanium Complexes ◽

G0 Phase ◽

Antibacterial And Anticancer Activity ◽

Dose Dependent

Abstract: Background: After the discovery of cisplatin, first non platinum anticancer drugs having excellent efficacy were budotitane and TiCl2(cp)2 but action mechanism is not clear. Therefore, we hereby reporting synthesis and biological activities novel titanium complexes to explore their mode of action. Objectives: Synthesis, spectral characterization, antibacterial and anticancer activity of some titanium complexes. Antibacterial studies on various bacterial strains and anticancer studies on HeLa, C6, CHO cancerous cell lines have been performed. Further, the cell death mechanistic study was done on CHO cell lines. Method: Titanium complexes with and without labile groups have been synthesized by reacting of TiCl4 with nitrogen containing ligands viz. 1,2-diaminocyclohexane, 1,10-Phenanthroline, adamantylamine, 2,2'-bipyridine, 4,4'-dimethyl-2,2'-bipyridine in predetermined molar ratios. Antibacterial and anticancer studies were performed by agar well diffusion method and MTT assay respectively. Cell cycle analysis is done by using flow cytometry. Results: Complex 2 i.e TiCl2(Phen)2 showed better activity than other complexes as an antibacterial as well as anticancer agent. Phase contrast imaging indicates that observed morphological changes of cells was dose dependent. Cell death mechanistic study have shown the increase in sub G0 phase population as well as formation of blebbing and fragmentation of chromatin material which is an indicative measure of apoptosis. Conclusion: Complex 2 proved to be more effective bactericide and cytotoxic agent. Cell cycle analysis showed cell arrest in G0 phase. Apoptosis percentage was found to increase in a dose dependent manner. So, prepared titanium complexes can be put to use as an important chemotherapeutic agents.

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Antitumor Effect of Pomolic Acid in Acute Myeloid Leukemia Cells Involves Cell Death, Decreased Cell Growth and Topoisomerases Inhibition

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180412120128 ◽

2019 ◽

Vol 18 (10) ◽

pp. 1457-1468

Author(s):

Michelle X.G. Pereira ◽

Amanda S.O. Hammes ◽

Flavia C. Vasconcelos ◽

Aline R. Pozzo ◽

Thaís H. Pereira ◽

...

Keyword(s):

Cell Cycle ◽

Cell Death ◽

Acute Myeloid Leukemia ◽

Cell Lines ◽

Myeloid Leukemia ◽

Natural Compound ◽

Dna Topoisomerases ◽

Human Dna ◽

Pomolic Acid ◽

Acute Myeloid

Background: Acute myeloid leukemia (AML) represents the largest number of annual deaths from hematologic malignancy. In the United States, it was estimated that 21.380 individuals would be diagnosed with AML and 49.5% of patients would die in 2017. Therefore, the search for novel compounds capable of increasing the overall survival rate to the treatment of AML cells is urgent. Objectives: To investigate the cytotoxicity effect of the natural compound pomolic acid (PA) and to explore the mechanism of action of PA in AML cell lines with different phenotypes. Methods: Three different AML cell lines, HL60, U937 and Kasumi-1 cells with different mechanisms of resistance were used to analyze the effect of PA on the cell cycle progression, on DNA intercalation and on human DNA topoisomerases (hTopo I and IIα) in vitro studies. Theoretical experiments of the inhibition of hTopo I and IIα were done to explore the binding modes of PA. Results: PA reduced cell viability, induced cell death, increased sub-G0/G1 accumulation and activated caspases pathway in all cell lines, altered the cell cycle distribution and inhibited the catalytic activity of both human DNA topoisomerases. Conclusion: Finally, this study showed that PA has powerful antitumor activity against AML cells, suggesting that this natural compound might be a potent antineoplastic agent to improve the treatment scheme of this neoplasm.

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Chitosan-Coated Gold Nanoparticles Induce Low Cytotoxicity and Low ROS Production in Primary Leucocytes, Independent of Their Proliferative Status

Pharmaceutics ◽

10.3390/pharmaceutics13070942 ◽

2021 ◽

Vol 13 (7) ◽

pp. 942

Author(s):

Helen Yarimet Lorenzo-Anota ◽

Diana G. Zarate-Triviño ◽

Jorge Alberto Uribe-Echeverría ◽

Andrea Ávila-Ávila ◽

José Raúl Rangel-López ◽

...

Keyword(s):

Gold Nanoparticles ◽

Cell Death ◽

Cancer Cells ◽

Cell Lines ◽

Mononuclear Cells ◽

Bone Marrow Cells ◽

Lymphoid Cells ◽

Ros Production ◽

Biomedical Sciences ◽

Peripheral Blood Mononuclear

(1) Background: Chitosan-coated gold nanoparticles (CH-AuNPs) have important theranostic applications in biomedical sciences, including cancer research. However, although cell cytotoxicity has been studied in cancerous cells, little is known about their effect in proliferating primary leukocytes. Here, we assessed the effect of CH-AuNPs and the implication of ROS on non-cancerous endothelial and fibroblast cell lines and in proliferative lymphoid cells. (2) Methods: The Turkevich method was used to synthetize gold nanoparticles. We tested cell viability, cell death, ROS production, and cell cycle in primary lymphoid cells, compared with non-cancer and cancer cell lines. Concanavalin A (ConA) or lipopolysaccharide (LPS) were used to induce proliferation on lymphoid cells. (3) Results: CH-AuNPs presented high cytotoxicity and ROS production against cancer cells compared to non-cancer cells; they also induced a different pattern of ROS production in peripheral blood mononuclear cells (PBMCs). No significant cell-death difference was found in PBMCs, splenic mononuclear cells, and bone marrow cells (BMC) with or without a proliferative stimuli. (4) Conclusions: Taken together, our results highlight the selectivity of CH-AuNPs to cancer cells, discarding a consistent cytotoxicity upon proliferative cells including endothelial, fibroblast, and lymphoid cells, and suggest their application in cancer treatment without affecting immune cells.

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Cytotoxicity and Apoptosis Effects of Curcumin Analogue (2E,6E)-2,6-Bis(2,3-Dimethoxybenzylidine) Cyclohexanone (DMCH) on Human Colon Cancer Cells HT29 and SW620 In Vitro

Molecules ◽

10.3390/molecules26051261 ◽

2021 ◽

Vol 26 (5) ◽

pp. 1261

Author(s):

Nurul Fattin Che Rahim ◽

Yazmin Hussin ◽

Muhammad Nazirul Mubin Aziz ◽

Nurul Elyani Mohamad ◽

Swee Keong Yeap ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cell Death ◽

Cancer Cells ◽

Cell Lines ◽

Curcuma Longa ◽

Metastatic Colon Cancer ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Sw620 Cell

Colorectal cancer (CRC) is the third most common type of cancer worldwide and a leading cause of cancer death. According to the Malaysian National Cancer Registry Report 2012–2016, colorectal cancer was the second most common cancer in Malaysia after breast cancer. Recent treatments for colon cancer cases have caused side effects and recurrence in patients. One of the alternative ways to fight cancer is by using natural products. Curcumin is a compound of the rhizomes of Curcuma longa that possesses a broad range of pharmacological activities. Curcumin has been studied for decades but due to its low bioavailability, its usage as a therapeutic agent has been compromised. This has led to the development of a chemically synthesized curcuminoid analogue, (2E,6E)-2,6-bis(2,3-dimethoxybenzylidine) cyclohexanone (DMCH), to overcome the drawbacks. This study aims to examine the potential of DMCH for cytotoxicity, apoptosis induction, and activation of apoptosis-related proteins on the colon cancer cell lines HT29 and SW620. The cytotoxic activity of DMCH was evaluated using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) cell viability assay on both of the cell lines, HT29 and SW620. To determine the mode of cell death, an acridine orange/propidium iodide (AO/PI) assay was conducted, followed by Annexin V/FITC, cell cycle analysis, and JC-1 assay using a flow cytometer. A proteome profiler angiogenesis assay was conducted to determine the protein expression. The inhibitory concentration (IC50) of DMCH in SW620 and HT29 was 7.50 ± 1.19 and 9.80 ± 0.55 µg/mL, respectively. The treated cells displayed morphological features characteristic of apoptosis. The flow cytometry analysis confirmed that DMCH induced apoptosis as shown by an increase in the sub-G0/G1 population and an increase in the early apoptosis and late apoptosis populations compared with untreated cells. A higher number of apoptotic cells were observed on treated SW620 cells as compared to HT29 cells. Human apoptosis proteome profiler analysis revealed upregulation of Bax and Bad proteins and downregulation of Livin proteins in both the HT29 and SW620 cell lines. Collectively, DMCH induced cell death via apoptosis, and the effect was more pronounced on SW620 metastatic colon cancer cells, suggesting its potential effects as an antimetastatic agent targeting colon cancer cells.

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Exploration of p53 plus interferon-beta gene transfer for the sensitization of human colorectal cancer cell lines to cell death

Cancer Biology & Therapy ◽

10.1080/15384047.2021.1899784 ◽

2021 ◽

pp. 1-10

Author(s):

Paulo Roberto Del Valle ◽

Samir Andrade Mendonça ◽

Fernanda Antunes ◽

Aline Hunger ◽

Rodrigo E Tamura ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Death ◽

Gene Transfer ◽

Cell Lines ◽

Cancer Cell ◽

Interferon Beta ◽

Human Colorectal Cancer ◽

Human Colorectal Cancer Cell ◽

Colorectal Cancer Cell Lines ◽

Beta Gene

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Kaempferol Induces Cell Death and Sensitizes Human Head and Neck Squamous Cell Carcinoma Cell Lines to Cisplatin

10.1007/5584_2020_603 ◽

2020 ◽

Author(s):

Mabel Catalán ◽

Catalina Rodríguez ◽

Ivonne Olmedo ◽

Javiera Carrasco-Rojas ◽

Diego Rojas ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Death ◽

Cell Carcinoma ◽

Head And Neck ◽

Cell Lines ◽

Squamous Cell ◽

Carcinoma Cell ◽

Human Head ◽

Neck Squamous Cell Carcinoma ◽

Carcinoma Cell Lines

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Kinase Inhibitors of DNA-PK, ATM and ATR in Combination with Ionizing Radiation Can Increase Tumor Cell Death in HNSCC Cells While Sparing Normal Tissue Cells

Genes ◽

10.3390/genes12060925 ◽

2021 ◽

Vol 12 (6) ◽

pp. 925

Author(s):

Eva-Maria Faulhaber ◽

Tina Jost ◽

Julia Symank ◽

Julian Scheper ◽

Felix Bürkel ◽

...

Keyword(s):

Cell Cycle ◽

Cell Death ◽

Side Effects ◽

Ionizing Radiation ◽

Cell Lines ◽

Normal Tissue ◽

Kinase Inhibitors ◽

Induced Response ◽

Tumor Control ◽

Tumor Cell Death

(1) Kinase inhibitors (KI) targeting components of the DNA damage repair pathway are a promising new type of drug. Combining them with ionizing radiation therapy (IR), which is commonly used for treatment of head and neck tumors, could improve tumor control, but could also increase negative side effects on surrounding normal tissue. (2) The effect of KI of the DDR (ATMi: AZD0156; ATRi: VE-822, dual DNA-PKi/mTORi: CC-115) in combination with IR on HPV-positive and HPV-negative HNSCC and healthy skin cells was analyzed. Cell death and cell cycle arrest were determined using flow cytometry. Additionally, clonogenic survival and migration were analyzed. (3) Studied HNSCC cell lines reacted differently to DDRi. An increase in cell death for all of the malignant cells could be observed when combining IR and KI. Healthy fibroblasts were not affected by simultaneous treatment. Migration was partially impaired. Influence on the cell cycle varied between the cell lines and inhibitors; (4) In conclusion, a combination of DDRi with IR could be feasible for patients with HNSCC. Side effects on healthy cells are expected to be limited to normal radiation-induced response. Formation of metastases could be decreased because cell migration is impaired partially. The treatment outcome for HPV-negative tumors tends to be improved by combined treatment.

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