scholarly journals Anticancer Activity of Marine SpongeHyrtiossp. Extract in Human Colorectal Carcinoma RKO Cells with Different p53 Status

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Hyun Kyung Lim ◽  
Woori Bae ◽  
Hyi-Seung Lee ◽  
Joohee Jung

Drug development using marine bioresources is limited even though the ocean occupies about 70% of the earth and contains a large number of biological materials. From the screening test of the marine sponge extracts, we foundHyrtiossp. sponge collected from Chuuk island, Micronesia. In this study, theHyrtiossp. extract was examined for anticancer activity against human colorectal carcinoma RKO cells that are wildtype for p53 and RKO-E6 that are p53 defective. TheHyrtiossp. extract dose-dependently inhibited viability in both cell lines. Multinucleation as an indication of mitotic catastrophe was also observed. Cytotoxicity tests gave significantly different results for RKO and RKO-E6 cells after 48 h exposure toHyrtiossp. extract. In RKO cells treated withHyrtiossp. extract, cell death occurred by induction of p53 and p21 proteins. In p53-defective RKO-E6 cells,Hyrtiossp. extract decreased expression of JNK protein and increased p21 protein. These results indicate thatHyrtiossp. extract induced apoptosisviadifferent pathways depending on p53 status and could be a good natural product for developing new anticancer drugs.

2020 ◽  
Vol 72 (1) ◽  
pp. 214-224 ◽  
Author(s):  
Tomasz Gębarowski ◽  
Benita Wiatrak ◽  
Katarzyna Gębczak ◽  
Beata Tylińska ◽  
Kazimierz Gąsiorowski

Abstract Background The p53 protein is a transcription factor for many genes, including genes involved in inhibiting cell proliferation and inducing apoptosis in genotoxically damaged and tumor-transformed cells. In more than 55% of cases of human cancers, loss of the essential function of p53 protein is found. In numerous reports, it has been shown that small molecules (chemical compounds) can restore the suppressor function of the mutant p53 protein in tumor cells. The aim of this study was to evaluate the potential anticancer activity of three newly synthesized olivacine derivatives. Methods The study was performed using two cell lines—CCRF/CEM (containing the mutant p53 protein) and A549 (containing a non-mutant, wild-type p53 protein). The cells were incubated with olivacine derivatives for 18 h and then assays were carried out: measurement of the amount of p53 and p21 proteins, detection of apoptosis, cell cycle analysis, and rhodamine 123 accumulation assay (evaluation of P-glycoprotein inhibition). Multiple-criteria decision analysis was used to compare the anticancer activity of the tested compounds. Results Each tested compound caused the reconstitution of suppressor activity of the p53 protein in cells with the mutant protein. In addition, one of the compounds showed significant antitumor activity in both wild-type and mutant cells. For all compounds, a stronger effect on the level of the p53 protein was observed than for the reference compound—ellipticine. Conclusions The observed effects of the tested new olivacine derivatives (pyridocarbazoles) suggest that they are good candidates for new anticancer drugs.


PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e99729 ◽  
Author(s):  
Chih-Chiang Chien ◽  
Ming-Shun Wu ◽  
Shing-Chuan Shen ◽  
Ching-Huai Ko ◽  
Chih-Hung Chen ◽  
...  

APOPTOSIS ◽  
2013 ◽  
Vol 18 (6) ◽  
pp. 739-750 ◽  
Author(s):  
Lenka Beranova ◽  
Antonio R. Pombinho ◽  
Jarmila Spegarova ◽  
Michal Koc ◽  
Magdalena Klanova ◽  
...  

Author(s):  
Bregje Oorschot ◽  
Arlene Oei ◽  
Anna Nuijens ◽  
Hans Rodermond ◽  
Ron Hoeben ◽  
...  

AbstractThe influence of p53 status on potentially lethal damage repair (PLDR) and DNA double-strand break (DSB) repair was studied in two isogenic human colorectal carcinoma cell lines: RKO (p53 wild-type) and RC10.1 (p53 null). They were treated with different doses of ionizing radiation, and survival and the induction of DNA-DSB were studied. PLDR was determined by using clonogenic assays and then comparing the survival of cells plated immediately with the survival of cells plated 24 h after irradiation. Doses varied from 0 to 8 Gy. Survival curves were analyzed using the linear-quadratic formula: S(D)/S(0) = exp-(αD+βD2). The γ-H2AX foci assay was used to study DNA DSB kinetics. Cells were irradiated with single doses of 0, 0.5, 1 and 2 Gy. Foci levels were studied in non-irradiated control cells and 30 min and 24 h after irradiation. Irradiation was performed with gamma rays from a 137Cs source, with a dose rate of 0.5 Gy/min. The RKO cells show higher survival rates after delayed plating than after immediate plating, while no such difference was found for the RC10.1 cells. Functional p53 seems to be a relevant characteristic regarding PLDR for cell survival. Decay of γ-H2AX foci after exposure to ionizing radiation is associated with DSB repair. More residual foci are observed in RC10.1 than in RKO, indicating that decay of γ-H2AX foci correlates with p53 functionality and PLDR in RKO cells.


Oncogene ◽  
2001 ◽  
Vol 20 (12) ◽  
pp. 1476-1485 ◽  
Author(s):  
Yong J Lee ◽  
Kun H Lee ◽  
Hyeong-Reh Choi Kim ◽  
J Milburn Jessup ◽  
Dai-Wu Seol ◽  
...  

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