Effect of brazilin on apoptosis and suppression of histone deacetylase in multiple myeloma U266 cells.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13514-e13514
Author(s):  
Bonglee Kim ◽  
Sung Hoon Kim

e13514 Background: Brazilin [7, 11b-dihydrobenz(b)indeno[1,2-d]pyran-3, 6a, 9, 10(6H)-tetrol] isolated from Caesalpinia sappan has been showed various biological activities such as anti-inflammationy, anti-bacteria and anti-platelet aggregation. However, there is no report on its anti-cancer activity. Methods: In the present study, the anti-cancer mechanism of brazilin was investigated on apoptosis and cell cycle arrest in human multiple myeloma U266 cells. Results: Brazilin significantly increased sub-G1 population and TUNEL-positive cells undergoing apoptosis. Also, brazilin activated caspase-3 and regulated the expression of Bcl-2 family proteins including Bax, Bcl-xL and Bcl-2, via mitochondria-dependent pathway. Futhermore, cell cycle analysis revealed that brazilin induced G2/M arrest of cell cycle along with apoptosis induction in U266 cells. Consistently, brazilin elevated the expression of cyclin-dependent kinase (CDK) inhibitor proteins p21 and p27 and activated G2 checkpoint-related proteins such as Chk1, Chk2 and γ-H2Ax. Of note, brazilin significantly inhibited the activity of histone deacetylases (HDACs), transcription factors involved in the regulation of apoptosis and cell cycle arrest and the expression of HDAC-1 and -2 at both protein and mRNA levels. Notably, brazilin significantly potentiated the cytotoxic effect of chemotherapeutic agents such as bortezomib or doxorubicin in U266 cells. Conclusions: Taken together, our findings suggest that brazilin has a chemotherapeutic potential, via HDAC-mediated apoptosis and G2/M arrest for multiple myeloma treatment.

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Hong Zhen ◽  
Yifei Zhang ◽  
Zhijia Fang ◽  
Zhiwei Huang ◽  
Chongge You ◽  
...  

Toona sinensisandMoschusare two herb materials used in traditional Chinese medicine, most commonly for their various biological activities. In this study, we investigated the inhibitory effect of three decoctions fromToona sinensis,Moschus,andToona sinensisandMoschusin combination on cell growth in several normal and cancer cell lines by cell viability assay. The results showed that the combined decoction exhibited the strongest anticancer effects, compared to two single decoctions. The observations indicated that the combined decoction did not induce cell apoptosis and autophagy in HeLa cells by fluorescence microscopy. Flow cytometry analysis revealed that the combined decoction arrested HeLa cell cycle progression in S-phase. After the decoction incubation, among 41 cell cycle related genes, eight were reduced, while five were increased in mRNA levels by real-time PCR assay. Western blotting showed that there were no apparent changes of protein levels of Cyclin E1, while P27 expression significantly declined and the levels of CDC7 and CDK7 obviously increased. The data suggest that the RB pathway is partially responsible for the decoction-induced S-phase cell cycle arrest in HeLa cells. Therefore, the combined decoction may have therapeutic potential as an anticancer formula for certain cancers.


Author(s):  
Fatma Ismail Alhmied ◽  
Ali Hassan Alammar ◽  
Bayan Mohammed Alsultan ◽  
Marooj Alshehri ◽  
Faheem Hyder Pottoo

Abstract:: Thymoquinone (TQ), the bioactive constituent of Nigella Sativa seeds is a well-known natural compound for the management of several types of cancers. The anti-cancer properties of thymoquinone are thought to be operated via intervening with various oncogenic pathways including cell cycle arrest, prevention of inflammation and oxidative stress, induction of invasion, metastasis, inhibition of angiogenesis, and apoptosis. As well as up-regulation and down-regulation of specific tumor suppressor genes and tumor promoting genes, respectively. Proliferation of various tumor cells is inhibited by TQ via induction of cell cycle arrest, disruption of the microtubule organization, and down regulating cell survival protein expression. TQ induces G1 phase cell cycle arrest in human breast cancer, colon cancer and osteosarcoma cells through inhibiting the activation of cyclin E or cyclin D and up-regulating p27and p21 a cyclin dependent kinase (Cdk) inhibitor. TQ concentration is a significant factor in targeting a particular cell cycle phase. While high concentration of TQ induced G2 phase arrest in human breast cancer (MCF-7) cells, low concentration causes S phase arrest. This review article provides mechanistic insights into the anti-cancer properties of thymoquinone.


2012 ◽  
Vol 4 (6) ◽  
pp. 1384-1388 ◽  
Author(s):  
YI-MIN CHENG ◽  
QI ZHU ◽  
YI-YUN YAO ◽  
YONG TANG ◽  
MING-MING WANG ◽  
...  

2021 ◽  
Vol 15 (11) ◽  
pp. 3313-3320
Author(s):  
Rashad Qasem Ali Othman ◽  
Abdelnaser A. Badawy ◽  
Mohammed M. Alruwaili ◽  
Mohammed A. El-magd

Background: Multidrug resistance (MDR) is one of the strategies developed by cancer cells to inhibit the anticancer potential of the majority of chemotherapeutic agents and almost results in treatment failure. Objective: This study aimed to evaluate the therapeutic potential of camel milk exosomes (CME) on multidrug-resistant human acute promyelocytic leukemia HL60 cells (HL60/RS) and to investigate whether this CME could potentiate the anticancer effect of Doxorubicin (DOX) and decrease its side effects. Results: CME alone or combined with DOX significantly induced HL60/RS cell viability loss, apoptosis, and cell cycle arrest at the G0/G1 phase, and downregulated MDR genes (Abcb1, Abcc1, Abcg2) as compared to cells treated with DOX alone. Additionally, CME and DOX co-treated nude mice had the lowest tumor volume, Abcb1, Abcc1, Abcg2, and Bcl2 expression, and the highest Bax and caspase3 expression in HL60/RS xenografts. This combined therapy also decreased DOX adverse effects as revealed by decreased liver damage enzymes and lipid peroxide (MDA) and increased hepatic antioxidant enzymes (SOD, CAT, GPx). Conclusion: CME increased sensitivity of HL60/RS to DOX through, at least in part, reduction of MDR genes, induction of apoptosis, and cell cycle arrest. Thus, CME may be used as safe adjuvants to DOX during cancer treatment. Keywords: Camel milk exosomes; Myeloid leukemia; HL60; Apoptosis; MDR


2008 ◽  
Vol 141 (4) ◽  
pp. 470-482 ◽  
Author(s):  
Patricia Maiso ◽  
Enrique M. Ocio ◽  
Mercedes Garayoa ◽  
Juan C. Montero ◽  
Francesco Hofmann ◽  
...  

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5016
Author(s):  
Aveen N. Adham ◽  
Mohamed Elamir F. Hegazy ◽  
Alaadin M. Naqishbandi ◽  
Thomas Efferth

Thymus vulgaris and Arctium lappa have been used as a folk remedy in the Iraqi Kurdistan region to deal with different health problems. The aim of the current study is to investigate the cytotoxicity of T. vulgaris and A. lappa in leukemia and multiple myeloma (MM) cell lines and determine the mode of cell death triggered by the most potent cytotoxic fractions of both plants in MM. Resazurin assay was used to evaluate cytotoxic and ferroptosis activity, apoptosis, and modulation in the cell cycle phase were investigated via Annexin V-FITC/PI dual stain and cell-cycle arrest assays. Furthermore, we used western blotting assay for the determination of autophagy cell death. n-Hexane, chloroform, ethyl acetate, and butanol fractions of T. vulgaris and A. lappa exhibited cytotoxicity in CCRF-CEM and CEM/ADR 5000 cell lines at concentration range 0.001–100 μg/mL with potential activity revealed by chloroform and ethyl acetate fractions. NCI-H929 displayed pronounced sensitivity towards T. vulgaris (TCF) and A. lappa (ACF) chloroform fractions with IC50 values of 6.49 ± 1.48 and 21.9 ± 0.69 μg/mL, respectively. TCF induced apoptosis in NCI-H929 cells with a higher ratio (71%), compared to ACF (50%) at 4 × IC50. ACF demonstrated more potent autophagy activity than TCF. TCF and ACF induced cell cycle arrest and ferroptosis. Apigenin and nobiletin were identified in TCF, while nobiletin, ursolic acid, and lupeol were the main compounds identified in ACF. T. vulgaris and A. lappa could be considered as potential herbal drug candidates, which arrest cancer cell proliferation by induction of apoptosis, autophagic, and ferroptosis.


2019 ◽  
Vol 51 (5) ◽  
pp. 517-523 ◽  
Author(s):  
Ting Zhang ◽  
Bo Li ◽  
Qilin Feng ◽  
Zhijian Xu ◽  
Cheng Huang ◽  
...  

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