scholarly journals Induction of apoptosis by Oleracein A and Oleracein B in HepG2 cancerous cells is mediated by ceramide generation, caspase-9/caspase-3 pathway activation, and oxidative damage

2022 ◽  
pp. 100047
Author(s):  
Hamidreza Khodajou-Masouleh ◽  
Masoud Mashhadi akbar Boojar ◽  
Sarah Khavari-Nejad ◽  
Gilda Karimi
Keyword(s):  
Oxidative Damage ◽  
Caspase 3 ◽  
Caspase 9 ◽  
Pathway Activation ◽  
Induction Of Apoptosis ◽  
Ceramide Generation ◽  
Cancerous Cells

Omi/HtrA2 and XIAP are components of platelet apoptosis signalling

2013 ◽  
Vol 109 (03) ◽  
pp. 532-539 ◽  
Author(s):  
Jeannine Winkler ◽  
Margaret Rand ◽  
Markus Schmugge ◽  
Oliver Speer
Keyword(s):  
Cytochrome C ◽  
Caspase 3 ◽  
Transmembrane Potential ◽  
Signalling Pathway ◽  
Ionophore A23187 ◽  
Caspase 9 ◽  
Cytochrome C Release ◽  
Thrombin Inhibition ◽  
Induction Of Apoptosis ◽  
Apoptotic Proteins

SummaryAlthough platelets possess the hallmarks of apoptosis such as activation of caspases, cytochrome c release and depolarisation of the mitochondrial transmembrane potential (ΔΨm), their entire apoptotic-signalling pathway is not totally understood. Therefore we studied the expression of various apoptotic proteins and found that platelets contain the pro-apoptotic proteins Omi/HtrA2 and Smac/Diablo, as well as their target the X-linked inhibitor of apoptosis XIAP. Omi/HtrA2 and Smac/Diablo were released from mitochondria into the platelet cytosol together with cytochrome c after induction of apoptosis by the Ca2+ ionophore A23187 or the BH3 mimetic ABT-737, and to a lesser extent, after platelet stimulation with collagen and thrombin. Inhibition of Omi/HtrA2 led to decreased levels of activated caspase-3/7 and caspase-9, but did not abolish loss of ΔΨm or prevent release of Omi/HtrA2 from mitochondria. These results indicate that platelets have a functional intrinsic apoptotic-signalling pathway including the pro-apoptotic protease Omi/HtrA2 and its target protein XIAP.

Synthesis of Silica Based Nanoparticles against the Proliferation of Human Prostate Cancer

2021 ◽  
Vol 21 ◽  
Author(s):  
Irem M. Durmus ◽  
Ilyas Deveci ◽  
Serdar Karakurt
Keyword(s):  
Prostate Cancer ◽  
Caspase 3 ◽  
Caspase 9 ◽  
Apoptotic Pathway ◽  
Caspase 12 ◽  
Ic50 Value ◽  
Gene And Protein Expression ◽  
Cell Death Gene ◽  
Ft Ir ◽  
Cancerous Cells

Background: Prostate cancer(PCa) has the second-highest morbidity and mortality rates in men. Possessing facile surface chemistry and unique optical properties make silica nanoparticles(SiO2-NPs) promising cancer therapy materials. Objective: This study aimed to investigate the effects of SiO2-NPs and their derivatives, including SiNP-NH2, SiNP-Cl, and SiNP-SH against PCa and clarify their molecular mechanism on cell death, gene, and protein expressions. Methods: Following the synthesis and derivation of SiO2-NPs, their characterization was carried out using TEM, DLS, BET, and FT-IR. Cytotoxic properties of the compounds were investigated against different human cancerous cells, including HUH-7, A549, DLD-1, HeLa, NCI-H295R, and PC-3, as well as human healthy epithelium cell line PNT1A. Results: SiNP-NH2, SiNP-Cl, and SiNP-SH dose-dependently inhibited the proliferation of PC-3 cells with an IC50 value as 55.46 µg/mL, 55.09 µg/mL and 72.89 µg/mL, respectively.SiNP-SH significantly(p<0.0001) inhibited metastasis and invasion of PC-3 cells(20.4% and 46.7%, respectively), and significantly(p<0.0001) increased early apoptosis(32.3%) when compared with non-treated cells. Protein and mRNA expressions of BcL-2, Bax, caspase-3, caspase-9, caspase-12, p53, Smad-4, Kras, and Nf-ĸB were also altered following the treatment of SiO2-NPs and its derivatives. Conclusion: Our results demonstrated that –SH functioned SiO2-NPs can prevent the proliferation of human PCa by increasing apoptosis by upregulating gene and protein expression of p53(TP53) as well as caspase-3, caspase-9, and caspase-12 in the apoptotic pathway. Besides, the increased level of Smad-4 has also implicated the decreased cell proliferation. Hence, low sized SiNP-SH nanoparticles might be a suitable candidate for the treatment of human PCa.

Induction of Apoptosis and Anti-Tumor Effects of a Novel Pan Inhibitor of Bcl-2 and Mcl-1 Apogossypolone (ApoG2) in Multiple Myeloma Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2601-2601
Author(s):  
Jie Lin ◽  
Yongji Wu ◽  
Shujie Wang ◽  
Dajun Yang ◽  
Yongqiang Zhao
Keyword(s):  
Cell Cycle ◽  
Multiple Myeloma ◽  
Growth Inhibition ◽  
Caspase 3 ◽  
Xenograft Model ◽  
Caspase 9 ◽  
Dna Ladder ◽  
Myeloma Cells ◽  
Induction Of Apoptosis

Abstract Multiple myeloma remains an incurable malignancy and overall survival has not been improved despite responses to conventional and high-dose chemotherapy. Over-expression of both Bcl-2 and Mcl-1 is frequent in multiple myeloma which renders myeloma cells resistant to apoptosis by chemotherapy, and overexpression is associated with relapse and poorer survival. Inhibition of the anti-apoptotic function of Bcl-2 family member proteins such as Bcl-2 and Mcl-1 represents an attractive new strategy for developing anticancer drugs. Apogossypolone (ApoG2) is a novel derivative of the naturally occurring polyphenolic compound gossypol which has aldehyde moieties removed and further modification to make it pharmaceutically more stable. More particularly, ApoG2 is a potent inhibitor of Mcl-1 and Bcl-2, with Ki value of 25 nM for Mcl-1, 35 nM for Bcl-2, respectively. In this study, trypan blue dye exclusion, Hoechst 33258 staining, DNA ladder formation and annexin-V-PI flow cytometric analysis were used to determine the cellular activities of ApoG2 on cell growth inhibition, cell viability, cell cycle and apoptosis. Cleavage of caspase-3 and caspase-9 was analyzed by colorimetirc assay. Xenograft model of Wus1 cells (from Peking Union Medical College Hospital) in nude mice were used to determine the antitumor activity of compounds. We found that ApoG2 resulted in a dose and time-dependent inhibition of multiple myeloma cell proliferation, with IC50 value to both U266 and Wus1 cells at 0.1 to 0.2 uM at 48 hours after treatment. ApoG2 effectively induced apoptosis of multiple myeloma cells as evidenced by typical morphological changes, transmission electron microscopy, DNA ladder formation and increase in the percentage of cells in subdiploid peak. Colorimetric assays further showed activation of both caspase-3 and caspase-9. In a parallel direct comparison study, ApoG2 was more potent than the parental compound gossypol in both growth inhibition and induction of apoptosis. Of interest, cell cycle analysis of both U266 and Wus1 cells treated with ApoG2 produced a slightly G2 arrest, increasing from 9.7% to 19.6% in U266 cells, and from 9.8% to 31.7% in Wus1 cells, respectively. This was different from gossypol which induced mainly G1 arrest. Preliminary in vivo antitumor activity of ApoG2 was examined in xenograft model of Wus1 cells in nude mice, and growth inhibition (T/C) of 32.7% and 33.4% was obtained at 60 mg/kg, and 40 mg/kg, respectively. In addition, there was no body weight loss for both treated groups in comparison with the vehicle treated mice. Our results demonstrated that a potent pan inhibitor of Bcl-2 and Mcl-1 ApoG2 had significant effect of antiproliferation and induction of apoptosis on multiple myeloma cells in vitro and in vivo. ApoG2 may represent a promising new anticancer agent with a novel molecular mechanism and warrant further investigation as a single agent or in combination for human multiple myeloma with Bcl-2/Mcl-1 overexpression.

Induction of Apoptosis by the Oolong Tea Polyphenol Theasinensin A through CytochromecRelease and Activation of Caspase-9 and Caspase-3 in Human U937 Cells

2000 ◽  
Vol 48 (12) ◽  
pp. 6337-6346 ◽  
Author(s):  
Min-Hsiung Pan ◽  
Yu-Chih Liang ◽  
Shoei-Yn Lin-Shiau ◽  
Nan-Qun Zhu ◽  
Chi-Tang Ho ◽  
...  
Keyword(s):  
Caspase 3 ◽  
U937 Cells ◽  
Tea Polyphenol ◽  
Caspase 9 ◽  
Oolong Tea ◽  
Induction Of Apoptosis

Baicalein, a component of Scutellaria radix from Huang-Lian-Jie-Du-Tang (HLJDT), leads to suppression of proliferation and induction of apoptosis in human myeloma cells

Blood ◽  
2005 ◽  
Vol 105 (8) ◽  
pp. 3312-3318 ◽  
Author(s):  
Zi Ma ◽  
Ken-ichiro Otsuyama ◽  
Shangqin Liu ◽  
Saeid Abroun ◽  
Hideaki Ishikawa ◽  
...  
Keyword(s):  
Cell Lines ◽  
Caspase 3 ◽  
Herbal Medicines ◽  
Myeloma Cell ◽  
Suppressive Effect ◽  
Caspase 9 ◽  
Myeloma Cells ◽  
Induction Of Apoptosis ◽  
Induced Apoptosis

Abstract In the search for a more effective adjuvant therapy to treat multiple myeloma (MM), we investigated the effects of the traditional Chinese herbal medicines Huang-Lian-Jie-Du-Tang (HLJDT), Gui-Zhi-Fu-Ling-Wan (GZFLW), and Huang-Lian-Tang (HLT) on the proliferation and apoptosis of myeloma cells. HLJDT inhibited the proliferation of myeloma cell lines and the survival of primary myeloma cells, especially MPC-1- immature myeloma cells, and induced apoptosis in myeloma cell lines via a mitochondria-mediated pathway by reducing mitochondrial membrane potential and activating caspase-9 and caspase-3. Further experiments confirmed that Scutellaria radix was responsible for the suppressive effect of HLJDT on myeloma cell proliferation, and the baicalein in Scutellaria radix showed strong growth inhibition and induction of apoptosis in comparison with baicalin or wogonin. Baicalein as well as baicalin suppressed the survival in vitro of MPC-1- immature myeloma cells rather than MPC-1+ myeloma cells from myeloma patients. Baicalein inhibited the phosphorylation of IkB-α, which was followed by decreased expression of the IL-6 and XIAP genes and activation of caspase-9 and caspase-3. Therefore, HLJDT and Scutellaria radix have an antiproliferative effect on myeloma cells, especially MPC-1- immature myeloma cells, and baicalein may be responsible for the suppressive effect of Scutellaria radix by blocking IkB-α degradation. (Blood. 2005;105:3312-3318)

scholarly journals Morroniside protect human granulosa cells against H2O2-induced oxidative damage via regulating Nrf2 and MAPK signaling pathway

2021 ◽  
Author(s):  
Yucong Ma ◽  
Guimin Hao ◽  
Xiaohua Lin ◽  
Zhiming Zhao ◽  
Aimin Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Granulosa Cells ◽  
Caspase 3 ◽  
Nuclear Translocation ◽  
Oocyte Quality ◽  
Mapk Signaling ◽  
Control Group ◽  
Caspase 9 ◽  
Jnk Pathway

Abstract Background Morroniside is the main ingredient of Cornus officinalis, which has an antioxidant effect. Ovarian granulosa cells (GCs) are responsible for regulating the development and atresia of follicles, which are susceptible to oxidative stress. In this study, we investigated whether morroniside could inhibit oxidative stress of GCs induced by hydrogen peroxide (H2O2), thus leading to improve oocyte quality. Methods The study was divided into 5 groups: control group, H2O2 group, morroniside (5 µM) + H2O2, morroniside (10 µM) + H2O2, Morroniside (20 µM) + H2O2. Cell survival rate was determined by CCK-8, ROS fluorescence level was determined by DCFH-DA probe, MDA, 8-OHdG, T-AOC, SOD, NQO1 and caspase-3 were determined by ELISA, SOD, NQO1, Bax, Bcl-2, caspase-3, caspase-9, Nrf2 and MAPKs protein expression were determined by Western blot, and Nrf2 nuclear translocation level was determined by immunofluorescence method. SPSS21.0 was used for statistical data analysis. Results After pretreatment with morroniside, the levels of ROS, MDA and 8-OHdG in ovarian GCs were significantly decreased. Morroniside significantly upregulated the level of p-Nrf2 and promoted the nuclear translocation level of Nrf2, which transcriptionally activated antioxidase SOD and NQO1. In addition, the levels of apoptosis-related proteins Bax, Bcl-2, caspase-3 and caspase-9 were significantly regulated via p38 and JNK pathway by morroniside. Conclusions These results suggested that morroniside could reduce oxidative damage and apoptosis of ovarian GCs induced by H2O2 in multiple ways, which provided a new idea for clinical improvement of oxidative stress in female reproductive system.

scholarly journals Induction of Apoptosis by Radix Paeoniae Alba Extract through Cytochrome c Release and the Activations of Caspase-9 and Caspase-3 in HL-60 Cells

2006 ◽  
Vol 29 (6) ◽  
pp. 1082-1086 ◽  
Author(s):  
Kang Beom Kwon ◽  
Eun Kyung Kim ◽  
Mi Jeong Han ◽  
Byung Cheul Shin ◽  
Yong Kweon Park ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Caspase 3 ◽  
Caspase 9 ◽  
Cytochrome C Release ◽  
Induction Of Apoptosis ◽  
Radix Paeoniae Alba

scholarly journals ClC-5 Downregulation Induces Osteosarcoma Cell Apoptosis by Promoting Bax and tBid Complex Formation

2021 ◽  
Vol 10 ◽  
Author(s):  
Fei Peng ◽  
Weisong Cai ◽  
Jianping Li ◽  
Haohuan Li
Keyword(s):  
Complex Formation ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Caspase 9 ◽  
Poor Overall Survival ◽  
Apoptotic Pathway ◽  
Normal Bone ◽  
Pathway Activation

Osteosarcoma is the most common malignant bone tumor. Chloride (Cl−) channels-mediated Cl− movement plays an important role in regulating the functions of various cancer cells, but its role in osteosarcoma remains unclear. In this study, we found that ClC-5 was increased in osteosarcoma tissues compared with normal bone tissues. Patients with high ClC-5 expression showed poor overall survival relative to those patients with low ClC-5 expression. Higher ClC-5 expression and lower intracellular Cl− concentration ([Cl−]i) were observed in osteosarcoma cells compared with normal osteoblasts. Lowering [Cl−]i increased the viability of osteosarcoma cells, which was markedly blocked by ClC-5 downregulation. Knockdown of ClC-5 significantly induced osteosarcoma cell apoptosis and increased the release of cytochrome c from mitochondria to cytosol, concomitantly with cleavage of caspase-9, caspase-3, and PARP. The effect of ClC-5 downregulation on osteosarcoma cell apoptosis and viability was abolished by caspase-3 and caspase-9 inhibitors, but not caspase-8 inhibitor. Furthermore, ClC-5 inhibition promoted Bax translocation from cytosol to mitochondria. Immunoprecipitation showed that ClC-5 interacted with Bax and ClC-5 downregulation enhanced Bax and tBid complex formation. Collectively, we demonstrate that ClC-5 downregulation induces osteosarcoma cell apoptosis via mitochondria-dependent apoptotic pathway activation by promoting Bax and tBid association and subsequent Bax translocation.

Sign in / Sign up

Export Citation Format

Share Document