scholarly journals Xylopine Induces Oxidative Stress and Causes G2/M Phase Arrest, Triggering Caspase-Mediated Apoptosis by p53-Independent Pathway in HCT116 Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Luciano de Souza Santos ◽  
Valdenizia Rodrigues Silva ◽  
Leociley Rocha Alencar Menezes ◽  
Milena Botelho Pereira Soares ◽  
Emmanoel Vilaça Costa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Lines ◽  
Cancer Cell ◽  
Caspase 3 ◽  
Cancer Cell Lines ◽  
Apoptosis Pathway ◽  
Phase Arrest ◽  
M Phase ◽  
Induced Apoptosis ◽  
Hct116 Cells

Xylopine is an aporphine alkaloid that has cytotoxic activity to cancer cells. In this study, the underlying mechanism of xylopine cytotoxicity was assessed in human colon carcinoma HCT116 cells. Xylopine displayed potent cytotoxicity in different cancer cell lines in monolayer cultures and in a 3D model of cancer multicellular spheroids formed from HCT116 cells. Typical morphology of apoptosis, cell cycle arrest in the G2/M phase, increased internucleosomal DNA fragmentation, loss of the mitochondrial transmembrane potential, and increased phosphatidylserine externalization and caspase-3 activation were observed in xylopine-treated HCT116 cells. Moreover, pretreatment with a caspase-3 inhibitor (Z-DEVD-FMK), but not with a p53 inhibitor (cyclic pifithrin-α), reduced xylopine-induced apoptosis, indicating induction of caspase-mediated apoptosis by the p53-independent pathway. Treatment with xylopine also caused an increase in the production of reactive oxygen/nitrogen species (ROS/RNS), including hydrogen peroxide and nitric oxide, but not superoxide anion, and reduced glutathione levels were decreased in xylopine-treated HCT116 cells. Application of the antioxidant N-acetylcysteine reduced the ROS levels and xylopine-induced apoptosis, indicating activation of ROS-mediated apoptosis pathway. In conclusion, xylopine has potent cytotoxicity to different cancer cell lines and is able to induce oxidative stress and G2/M phase arrest, triggering caspase-mediated apoptosis by the p53-independent pathway in HCT116 cells.

scholarly journals Capsaicin induces apoptosis by generating reactive oxygen species and disrupting mitochondrial transmembrane potential in human colon cancer cell lines

2009 ◽  
Vol 14 (3) ◽  
Author(s):  
Kyung Yang ◽  
Jong Pyo ◽  
Gyu-Yeol Kim ◽  
Rina Yu ◽  
In Han ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Caspase 3 ◽  
Cancer Cell Lines ◽  
Colon Cancer Cell ◽  
Enzyme Treatment ◽  
Dependent Manner ◽  
Colon Cancer Cell Lines ◽  
Induced Apoptosis

AbstractAlthough genetic factors are a well-known cause of colorectal cancer, environmental factors contribute more to its development. Despite advances in the fields of surgery, radiotherapy and chemotherapy, the cure rates for colon cancer have not substantially improved over the past few decades. Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), the principal pungent ingredient of hot chili pepper, has exhibited an anti-tumor effect in many cell types. However, the mechanisms responsible for the anti-tumor effect of capsaicin are not yet completely understood. In this study, we investigated whether capsaicin induces apoptosis in colon cancer cell lines. Capsaicin decreased cell viability in a dose-dependent manner in Colo320DM and LoVo cells. In addition, capsaicin produced cell morphology changes and DNA fragmentation, decreased the DNA contents, and induced phosphatidylserine translocation, which is a hallmark of apoptotic cell death. We showed that capsaicin-induced apoptosis is associated with an increase in ROS generation and a disruption of the mitochondrial transmenbrane potential. A possible mechanism of capsaicin-induced apoptosis is the activation of caspase 3, a major apoptosis-executing enzyme. Treatment with capsaicin induced a dramatic increase in caspase 3 activity, as assessed by the cleavage of Ac-DEVD-AMC, a fluorogenic substrate. In conclusion, our results clearly showed that capsaicin induced apoptosis in colon cancer cells. Although the actual mechanisms of capsaicin-induced apoptosis remain uncertain, it may be a beneficial agent for colon cancer treatment and chemoprevention.

scholarly journals A Novel Ruthenium(II) Complex With Lapachol Induces G2/M Phase Arrest Through Aurora-B Kinase Down-Regulation and ROS-Mediated Apoptosis in Human Prostate Adenocarcinoma Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Rone A. De Grandis ◽  
Katia M. Oliveira ◽  
Adriana P. M. Guedes ◽  
Patrick W. S. dos Santos ◽  
Alexandre F. Aissa ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Prostate Adenocarcinoma ◽  
Human Prostate ◽  
Aurora B ◽  
Phase Arrest ◽  
Adenocarcinoma Cells ◽  
M Phase

Lapachol is a well-studied natural product that has been receiving great interest due to its anticancer properties that target oxidative stress. In the present work, two novel lapachol-containing ruthenium(II) complexes [Ru(Lap)(dppm)(bipy)]PF6 (1) and [Ru(Lap)(dppm)(phen)]PF6 (2) [Lap = lapachol, dppm = 1,1′-bis(diphosphino)methane, bipy = 2,2′-bipyridine, phen = 1,10-phenantroline] were synthesized, fully characterized, and investigated for their cellular and molecular responses on cancer cell lines. We found that both complexes exhibited a potent cytotoxic effect in a panel of cancer cell lines in monolayer cultures, as well as in a 3D model of multicellular spheroids formed from DU-145 human prostate adenocarcinoma cells. Furthermore, the complex (2) suppressed the colony formation, induced G2/M-phase arrest, and downregulated Aurora-B. The mechanism studies suggest that complex (2) stimulate the overproduction of reactive oxygen species (ROS) and triggers caspase-dependent apoptosis as a result of changes in expression of several genes related to cell proliferation and caspase-3 and -9 activation. Interestingly, we found that N-acetyl-L-cysteine, a ROS scavenger, suppressed the generation of intracellular ROS induced by complex (2), and decreased its cytotoxicity, indicating that ROS-mediated DNA damage leads the DU-145 cells into apoptosis. Overall, we highlighted that coordination of lapachol to phosphinic ruthenium(II) compounds considerably improves the antiproliferative activities of resulting complexes granting attractive selectivity to human prostate adenocarcinoma cells. The DNA damage response to ROS seems to be involved in the induction of caspase-mediated cell death that plays an important role in the complexes' cytotoxicity. Upon further investigations, this novel class of lapachol-containing ruthenium(II) complexes might indicate promising chemotherapeutic agents for prostate cancer therapy.

Arsenic trioxide-induced apoptosis through oxidative stress in cells of colon cancer cell lines

Life Sciences ◽  
2002 ◽  
Vol 70 (19) ◽  
pp. 2253-2269 ◽  
Author(s):  
Yoshihito Nakagawa ◽  
Yukihiro Akao ◽  
Hiroshi Morikawa ◽  
Ichiro Hirata ◽  
Kenichi Katsu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colon Cancer ◽  
Arsenic Trioxide ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Colon Cancer Cell ◽  
Colon Cancer Cell Lines ◽  
Induced Apoptosis ◽  
In Cells

scholarly journals Comprehensive Evaluation of Biological Effects of Pentathiepins on Various Human Cancer Cell Lines and Insights into Their Mode of Action

2021 ◽  
Vol 22 (14) ◽  
pp. 7631
Author(s):  
Lisa Wolff ◽  
Siva Sankar Murthy Bandaru ◽  
Elias Eger ◽  
Hoai-Nhi Lam ◽  
Martin Napierkowski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Biological Effects ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Human Cancer Cell ◽  
Strand Breaks ◽  
Human Cancer Cell Lines

Pentathiepins are polysulfur-containing compounds that exert antiproliferative and cytotoxic activity in cancer cells, induce oxidative stress and apoptosis, and inhibit glutathione peroxidase (GPx1). This renders them promising candidates for anticancer drug development. However, the biological effects and how they intertwine have not yet been systematically assessed in diverse cancer cell lines. In this study, six novel pentathiepins were synthesized to suit particular requirements such as fluorescent properties or improved water solubility. Structural elucidation by X-ray crystallography was successful for three derivatives. All six underwent extensive biological evaluation in 14 human cancer cell lines. These studies included investigating the inhibition of GPx1 and cell proliferation, cytotoxicity, and the induction of ROS and DNA strand breaks. Furthermore, selected hallmarks of apoptosis and the impact on cell cycle progression were studied. All six pentathiepins exerted high cytotoxic and antiproliferative activity, while five also strongly inhibited GPx1. There is a clear connection between the potential to provoke oxidative stress and damage to DNA in the form of single- and double-strand breaks. Additionally, these studies support apoptosis but not ferroptosis as the mechanism of cell death in some of the cell lines. As the various pentathiepins give rise to different biological responses, modulation of the biological effects depends on the distinct chemical structures fused to the sulfur ring. This may allow for an optimization of the anticancer activity of pentathiepins in the future.

High-risk HPV-positive human cancer cell lines show different sensitivity to cisplatin-induced apoptosis correlated with the p21Waf1/Cip1 level

1996 ◽  
Vol 108 (1) ◽  
pp. 15-23 ◽  
Author(s):  
Kohsei Funaoka ◽  
Masanobu Shindoh ◽  
Toshiharu Yamashita ◽  
Kei Fujinaga ◽  
Akira Amemiya ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
Induced Apoptosis ◽  
High Risk Hpv

Expression patterns of miR-221 and its target Caspase-3 in different cancer cell lines

2014 ◽  
Vol 41 (9) ◽  
pp. 5877-5881 ◽  
Author(s):  
Sercan Ergun ◽  
Kaifee Arman ◽  
Ebru Temiz ◽  
İbrahim Bozgeyik ◽  
Önder Yumrutaş ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Caspase 3 ◽  
Expression Patterns ◽  
Cancer Cell Lines

Enhancement of 5-Aminolevulinic acid-induced oxidative stress on two cancer cell lines by gold nanoparticles

2009 ◽  
Vol 43 (12) ◽  
pp. 1214-1224 ◽  
Author(s):  
Shinji Ito ◽  
Norio Miyoshi ◽  
William G. Degraff ◽  
Kunio Nagashima ◽  
Louis J. Kirschenbaum ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gold Nanoparticles ◽  
Cell Lines ◽  
Cancer Cell ◽  
Aminolevulinic Acid ◽  
Cancer Cell Lines

scholarly journals Synthesis and Biological Activity of 2-Arylidene-N-(quinolin-6-yl)hydrazine-1-carboxamides

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Shengxian Zhao ◽  
Yin Cao ◽  
Zhenzhen Cui ◽  
Jiayun Zhang ◽  
Zhixiang Pan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Colony Formation Assay ◽  
M Phase ◽  
Antiproliferative Activities ◽  
Mcf 7

A series of 2-arylidene-N-(quinolin-6-yl)hydrazine-1-carboxamides 5a–5o were synthesized and characterized. The synthesized compounds (5a–5o) were screened in vitro against three breast cancer cell lines: SKBR3, MDA-MB-231, and MCF-7 cancer cell lines by the MTT assay. According to MTT results, compounds 5k and 5l showed better antiproliferative activities over MCF-7 cell lines with IC50 values of 8.50 and 12.51 μM. Colony formation assay indicated 5k/5l treatment obviously inhibited the growth of MCF-7 cells and 5k/5l-induced cell cycle was arrested in the G2-M phase. Moreover, 5k/5l significantly increased the level of cleaved PARP and induced the apoptosis in MCF-7 cells. In addition, compared to Hela cells, MCF-7 cells were more sensitive to 5k/5l treatment.

scholarly journals Cytotoxic Constituents of the Bark of Hypericum roeperianum towards Multidrug-Resistant Cancer Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Michel-Gael F. Guefack ◽  
Francois Damen ◽  
Armelle T. Mbaveng ◽  
Simplice Beaudelaire Tankeo ◽  
Gabin T. M. Bitchagno ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Colon Adenocarcinoma ◽  
Cancer Cell Lines ◽  
Multidrug Resistant ◽  
Leukemia Cells ◽  
Ros Production ◽  
Cytotoxic Effects ◽  
Induced Apoptosis

The global cancer burden remains a serious concern with the alarming incidence of one in eight men and one in eleven women dying in developing countries. This situation is aggravated by the multidrug resistance (MDR) of cancer cells that hampers chemotherapy. In this study, the cytotoxicity of the methanol extract (HRB), fractions (HRBa, HRBb, and HRBa1-5), and compounds from the bark of Hypericum roeperianum (HRB) was evaluated towards a panel of 9 cancer cell lines. The mode of action of the HRB and trichadonic acid (1) was also studied. Column chromatography was applied to isolate the constituents of HRB. The cytotoxicity of botanicals and phytochemicals was evaluated by the resazurin reduction assay (RRA). Caspase-Glo assay was used to evaluate the activity of caspases, and reactive oxygen species (ROS) (H2DCFH-DA) were assessed by flow cytometry. Phytochemicals isolated from HRB were trichadonic acid (1), fridelan-3-one (2), 2-hydroxy-5-methoxyxanthone (3), norathyriol (4), 1,3,5,6-tetrahydroxyxanthone (5), betulinic acid (6), 3′-hydroxymethyl-2′-(4″-hydroxy-3″,5″-dimethoxyphenyl)-5′,6′:5,6-(6,8-dihydroxyxanthone)-1′,4′-dioxane (7), and 3′-hydroxymethyl-2′-(4″-hydroxy-3″,5″-dimethoxyphenyl)-5′,6′:5,6-(xanthone)-1′,4′-dioxane (8). Botanicals HRB, HRBa, HRBa2-4, HRBb, and doxorubicin displayed cytotoxic effects towards the 9 tested cancer cell lines. The recorded IC50 values ranged from 11.43 µg/mL (against the P-glycoprotein (gp)-overexpressing CEM/ADR5000 leukemia cells) to 26.75 µg/mL (against HCT116 (p53+/+) colon adenocarcinoma cells) for the crude extract HRB. Compounds 1, 5, and doxorubicin displayed cytotoxic effects towards the 9 tested cancer cell lines with IC50 values varying from 14.44 µM (against CCRF-CEM leukemia cells) to 44.20 µM (against the resistant HCT116 (p53−/−) cells) for 1 and from 38.46 µM (against CEM/ADR5000 cells) to 112.27 µM (against the resistant HCT116 (p53−/−) cells) for 5. HRB and compound 1 induced apoptosis in CCRF-CEM cells. The apoptotic process was mediated by enhanced ROS production for HRB or via caspases activation and enhanced ROS production for compound 1. This study demonstrated that Hypericum roeperianum is a potential source of cytotoxic phytochemicals such as trichadonic acid and could be further exploited in cancer chemotherapy.

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