Comparison of traditional Chinese medicine (TCM) herbal mixture LQ and paclitaxel on the phase of cancer cell cycle blockage and cancer cell invasion.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22014-e22014
Author(s):  
Robert M. Hoffman ◽  
Chengyu Wu ◽  
Shuya Yano ◽  
Lei Zhang

e22014 Background: Although Traditional Chinese Medicine (TCM) has been used to treat cancer for thousands of years, the mechanisms of action are either poorly understood or unknown. In the present report, we use state-of-the-art technology to investigate the anti-cancer mechanism of the TCM herbal mixture LQ. Methods: Fluorescence ubiquitination-based cell cycle indicator (FUCCI) was used to monitor cell cycle arrest HeLa cells after LQ treatment. FUCCI-HeLa cells were cultured in two dimensional (2D) monolayer, Matrigel and 3D Gelfoam. Changes of cell cycle status were observed using the Olympus FV1000 confocal imaging system whereby cycling cells fluoresce green and quiescent cells red. Paclitaxel (Taxol) was used as the positive control. Results: Paclitaxel induced a G2/M cell cycle block. In contrast, LQ blocked FUCCI-HeLa cells in the G0/G1 phase of the cell cycle in all 3 culture models. In monolayer culture, the paclitaxel positive control had approximately 45% of the cells in G2/M phase. In contrast, the LQ-treated cells were mostly in the G0/G1 phase (>90%). In Matrigel culture, HeLa cells formed spheres. The spheres in the paclitaxel control group had 40% of the cells in G2/M phase, but only 15% in LQ-treated cultures. In 3D Gelfoam culture, cells grew along the structures of the Gelform. The paclitaxel positive control culture had approximately 45% of cells in G2/M phase. In contrast, the cells in LQ-treated culture were mostly in G0/G1 phase (>80%). The cells in pacilitaxel control group invaded to 250~300 µm deep in the Gelfoam, but only 150~200 µm deep in LQ-treated culture. Conclusions: The anti-cancer mechanism of TCM herbal mixture LQ involves cancer cell cycle arrest at G0/G1 and inhibition of cancer cell invasion.

2021 ◽  
Vol 12 ◽  
Author(s):  
Guangya Xu ◽  
Xueling Yan ◽  
Zhongjia Hu ◽  
Lulu Zheng ◽  
Ke Ding ◽  
...  

Glucocappasalin (GCP), a natural product derived from the seeds of Descurainia sophia (L.) Webb. ex Prantl, exhibits potential antitumor activity in HeLa cervical carcinoma cells. In this study, we investigated the anti-cervical cancer property of GCP through the induction of cell cycle arrest, apoptosis, and autophagy in vitro and in vivo, and elucidated the underlying molecular mechanisms. We demonstrated that treatment with GCP inhibited the growth of HeLa, Siha, and Ca Ski cell lines in a dose-dependent manner, with HeLa cells displaying particular sensitivity to the GCP treatment. Subsequently, the expression of cyclin-dependent kinase 1 (CDK1) and polo like kinase 1 (PLK1) were evaluated in HeLa cells using the CDK1 kinase assay kit, the fluorescence polarization assay, real-time quantitative PCR, and western blotting. Our results demonstrate that GCP could be employed to attenuate the expression of CDK1 and PLK1 in a dose- and time-dependent manner. The complementary results obtained by flow cytometry and western blotting allowed us to postulate that GCP may exhibit its antitumor effects by inducing G2/M cell cycle arrest. Moreover, HeLa cells treated with GCP exhibited a loss in mitochondrial membrane potential, together with the activation of caspases 3 and 9, and poly ADP-ribose polymerase (PARP). Additionally, we found that GCP could increase the formation of acidic vesicular organelles (AVOs), as well as the levels of Beclin1, LC3-II, p62, and Atg5 proteins in HeLa cells. Further studies indicated that GCP triggered autophagy via the suppression of the PI3K/AKT/mTOR signaling pathways. The autophagy inhibitor 3-methyladenine (3-MA) was used to determine whether autophagy affects the apoptosis induced by GCP. Interestingly, the inhibition of autophagy attenuated apoptosis. In vivo anti-tumor experiments indicated that GCP (60 mg/kg, i.p.) markedly reduced the growth of HeLa xenografts in nude mice without apparent toxicity. Taken together, we demonstrate that GCP induces cell cycle G2/M-phase arrest, apoptosis, and autophagy by acting on the PI3K/AKT/mTOR signaling pathways in cervical carcinoma cells. Thus, GCP may represent a promising agent in the eradication of cervical cancer.


Planta Medica ◽  
2021 ◽  
Author(s):  
Thi Thu Ha Nguyen ◽  
Zhao Qu ◽  
Van Tuyen Nguyen ◽  
Thanh Tra Nguyen ◽  
Thi Tu Anh Le ◽  
...  

Three prenylated xanthones, garcinone E (1), bannaxanthone D (2) and bannanxanthone E (3) were isolated from the leaves of Garcinia mckeaniana Graib. Their structures were elucidated by spectral methods and compared with literature data. To evaluate their anti-proliferative effects in tumor cells, firstly, cisplatin was used as a positive control and the effects of compound 1-3 were determined by performing MTT assay in MDA-MB-231, CNE-2 and A549 cancer cells. The results showed compound 1-3 exhibited stronger inhibitory effect than cisplatin in MDA-MB-231. Further effects of compound 1-3 in TNBC MDA-MB-231 and MDA-MB-468 cells were examined by performing cell cycle and apoptosis assays. The results indicated that compound 1-3 had ability to arrest cell cycle at G2/M phase and induce apoptosis. Furthermore, compound 2 significantly down-regulated PI3K, Akt and mTOR levels in both total proteins and phosphorylated form, which is its potential anti-cancer mechanism. These findings indicated that those prenylated xanthones might serve as promising leading compounds for the development of anticancer drug for TNBC.


2021 ◽  
Author(s):  
Hüseyin Abdik

Abstract Background: Lung cancer (LC) is one of the most common types of cancer with a high mortality rate. Depending on molecular and histological properties, LC is divided into non–small-cell and small-cell lung cancer. Not only surgery but also radiotherapy, chemotherapy, or combination treatment are used for patients. However, the survival rate of LC is still very low. Erufosine (ErPC3) is a novel promising antineoplastic agent and inhibits the translocation of AKT to the plasma membrane by dephosphorylating AKT. Methods and Results: In the current study, the cell-type dependent effects of ErPC3 on cell viability, apoptotic situation, cell cycle distribution, related gene expression, and migration capacities of A549 and DMS 114 were investigated. As results, ErPC3 exhibited cytotoxic and pro-apoptotic properties against both cells, while DMS 114 was more affected. ErPC3 accumulated the cells in G2/M phase and blocked cell cycle. Proliferation markers were downregulated, while pro-apoptotic markers were upregulated in ErPC3 treated cells. Besides, ErPC3 displayed anti-migratory effect on A549 and DMS 114 compared to the control group according to scratch assay. Conclusion: These findings promise a treatment approach and drug development against LC. The obtained results from the recent study lead it necessary to carry out more detailed studies about ErPC3.


Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1996 ◽  
Author(s):  
Bartolomeo Bosco ◽  
Andrea Defant ◽  
Andrea Messina ◽  
Tania Incitti ◽  
Denise Sighel ◽  
...  

Reversine is a potent antitumor 2,6-diamino-substituted purine acting as an Aurora kinases inhibitor and interfering with cancer cell cycle progression. In this study we describe three reversine-related molecules, designed by docking calculation, that present structural modifications in the diamino units at positions 2 and 6. We investigated the conformations of the most stable prototropic tautomers of one of these molecules, the N6-cyclohexyl-N6-methyl-N2-phenyl-7H-purine-2,6-diamine (3), by Density Functional Theory (DFT) calculation in the gas phase, water and chloroform, the last solvent considered to give insights into the detection of broad signals in NMR analysis. In all cases the HN(9) tautomer resulted more stable than the HN(7) form, but the most stable conformations changed in different solvents. Molecules 1–3 were evaluated on MCF-7 breast and HCT116 colorectal cancer cell lines showing that, while being less cytotoxic than reversine, they still caused cell cycle arrest in G2/M phase and polyploidy. Unlike reversine, which produced a pronounced cell cycle arrest in G2/M phase in all the cell lines used, similar concentrations of 1–3 were effective only in cells where p53 was deleted or down-regulated. Therefore, our findings support a potential selective role of these structurally simplified, reversine-related molecules in p53-defective cancer cells.


2019 ◽  
Vol 20 (5) ◽  
pp. 1217 ◽  
Author(s):  
Bresler Swanepoel ◽  
Luanne Venables ◽  
Octavian Olaru ◽  
George Nitulescu ◽  
Maryna van de Venter

Anemone nemorosa is part of the Ranunculaceae genus Anemone (order Ranunculales) which comprises more than 150 species. Various parts of the plant have been used for the treatment of numerous medical conditions such as headaches, tertian agues, rheumatic gout, leprosy, lethargy, eye inflammation as well as malignant and corroding ulcers. The Anemone plants have been found to contain various medicinal compounds with anti-cancer, immunomodulatory, anti-inflammatory, anti-oxidant and anti-microbial activities. To date there has been no reported evidence of its use in the treatment of cancer. However, due to the reported abundance of saponins which usually exert anti-cancer activity via cell cycle arrest and the induction of apoptosis, we investigated the mode of cell death induced by an aqueous A. nemorosa extract by using HeLa cervical cancer cells. Cisplatin was used as a positive control. With a 50% inhibitory concentration (IC50) of 20.33 ± 2.480 µg/mL, treatment with A. nemorosa yielded a delay in the early mitosis phase of the cell cycle. Apoptosis was confirmed through fluorescent staining with annexin V-FITC. Apoptosis was more evident with A. nemorosa treatment compared to the positive control after 24 and 48 h. Tetramethylrhodamine ethyl ester staining showed a decrease in mitochondrial membrane potential at 24 and 48 h. The results obtained imply that A. nemorosa may have potential anti-proliferative properties.


2010 ◽  
Vol 20 (23) ◽  
pp. 7054-7058 ◽  
Author(s):  
Jifeng Wang ◽  
Baobing Zhao ◽  
Wei Zhang ◽  
Xuan Wu ◽  
Ruoyu Wang ◽  
...  

BIOCELL ◽  
2014 ◽  
Vol 38 (1) ◽  
pp. 17-24
Author(s):  
Yanhong ZHEN ◽  
Li HAN ◽  
Kailai CAI ◽  
Lijun HUO ◽  
Hasan RIAZ ◽  
...  

2020 ◽  
Vol 12 (4) ◽  
pp. 376-383
Author(s):  
Diah Tri Utami ◽  
Nadzifa Nugraheni ◽  
Riris Istighfari Jenie ◽  
Edy Meiyanto

BACKGROUND: The presence of adverse side effects limits the use of doxorubicin (Dox) despite its cost-effectiveness compared to other chemotherapeutic agents. Brazilein (Be), the major compound of Caesalpinia sappan, performs co-chemotherapeutic potency in several cancer cell lines. This study evaluates the chemosensitizing effects of Be to Dox on colon cancer cell line, WiDr.METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was conducted to evaluate the cytotoxic effect of Be and its combination with Dox. The synergistic effect of Be and Dox was examined by using the Combination index (CI) parameter. Cell cycle and apoptosis profiles were done using flow cytometry with propidium iodide (PI)/RNase and Annexin V staining, respectively.RESULTS: The combination of Dox and Be at half of IC50 on WiDr cells showed a synergistic effect with a combination index of 0.4. Analysis of the cell cycle revealed that the combination caused cell cycle termination at the S and G2/M phase. This finding corresponded with the data that single treatment of Dox and Be induced cell cycle arrest at the different phases, namely S and G2/M phase, respectively. However, the combination treatment for 24 hours did not induce apoptosis. This combination should be further clarified as there was a possibility that many cells may underwent permanently arrest that halts to proceed apoptosis.CONCLUSION: Our findings suggested that Be synergizes with Dox to suppress the growth of WiDr cells via cell cycle arrest, hence, Be is potential to be developed as a co-chemotherapeutic agent. Our findings suggested that Be synergizes with Dox to suppress the growth of WiDr cells via cell cycle arrest, hence, Be is potential to be developed as a co-chemotherapeutic agent.KEYWORDS: Brazilein, colon cancer WiDr, co-treatment, Doxorubicin, cell cycle arrest


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