scholarly journals Study of Synergistic and Protective Effects of Three Different Polar Saffron Extracts and Photon Radiation on Human Colorectal Cancer Cells (HT-29) and Normal Human Fibroblasts

2020 ◽  
Vol 13 (12) ◽  
Author(s):  
Mahnaz Nourbakhsh ◽  
Amin Hosseinzade ◽  
Jamshidkhan Chamani ◽  
Ameneh Sazgarnia ◽  
Roham Salek

Background: There are some hypotheses about radiation-sensitizing and radiation-protective effects of antioxidants. Saffron, dried stigmas of Crocus sativus L., is a precious medicinal plant that contains an impressive variety of plant compounds such as crocin, crocetin, and safranal that act as antioxidants. The present study examined the cytotoxic effects of saffron extracts with different polarity and their synergism or protective effects with radiation on a colorectal cancer cell line (HT-29) and normal human fibroblasts. Objectives: The aim was to find a natural agent to improve radiotherapy efficacy. Methods: HT-29 colorectal cancer cells and normal human fibroblasts were cultured in RPMI1640 medium, incubated with different concentrations of different saffron extracts (50-250 µg/ml), and then were exposed to a dose of 8 Gy of X-rays. The cytotoxicity effect was determined by the MTT assay. Results: Saffron extracts decreased cell viability in HT-29 colorectal cancer cells and normal human fibroblasts as a concentration-dependent manner. Combination radiotherapy with polar saffron extract in most doses showed synergistic effects on HT-29 cell death while it did not show any distinctive synergistic effect in normal cells. Semi-polar and non-Polar extracts just in low doses had synergistic effects on tumor cells. These two extracts did not show any protective effects on normal cells. Conclusions: Among the various saffron extracts, polar saffron extract and low doses of non-polar saffron extract in combination with radiation increase radiation sensitivity and cell death in tumor cells, while they do not increase radiation sensitivity in normal cells and even protect normal cells to some extent.

2021 ◽  
pp. 100995
Author(s):  
Shengchang Tao ◽  
Chunlei Huang ◽  
Zhihong Tan ◽  
Shuna Duan ◽  
Xiaofeng Zhang ◽  
...  

2021 ◽  
Vol 7 (1) ◽  
pp. 6
Author(s):  
Sareh Kamran ◽  
Ajantha Sinniah ◽  
Mohammed Abdullah Alshawsh

Colorectal cancer (CRC) is among the most commonly occurring cancers. The management of CRC includes laparoscopic surgery, radiotherapy, chemotherapies and neoadjuvant treatment. However, conventional chemotherapies have poor impact on combating CRC and are associated with severe toxic effects and high rates of relapse. Therefore, searching for a new combination regimen is a favorable consideration. The aim of this study was to elucidate the synergistic effect of 5-fluorouracil (5-FU) and diosmetin in an in vitro model on colorectal cancer cells. An MTT assay was conducted on HCT-116 cancer cells and they were treated with a concentration gradient of 5-FU and diosmetin individually and in combination. The combination index (CI) and dose reduction index (DRI) were calculated using CompuSyn software. Isobologram analysis and synergism determination were performed using the Combenefit software tool and the synergy score was calculated using the SynergyFinder 2.0 software tool. The apoptotic features of the cells were determined via an AO/PI double staining assay and an annexin V assay using a fluorescent microscope and the flow cytometry technique, respectively. The findings showed that the DRI of 5-FU was three-fold lower in the combination with a CI value of less than one, which indicates that there was a synergistic effect. The AO/PI microscopic results revealed signs of apoptosis and dead cells after 72 h of treatment. Flow cytometry analysis confirmed that the apoptotic effect of the combination was more prominent compared to 5-FU alone. The findings of this study offer a potential strategy for reducing the cytotoxicity and enhancing the efficacy of 5-FU on colorectal cancer cells through a synergistic study model.


2015 ◽  
Vol 117 (5) ◽  
pp. 1262-1272 ◽  
Author(s):  
Nadia Mustapha ◽  
Aline Pinon ◽  
Youness Limami ◽  
Alain Simon ◽  
Kamel Ghedira ◽  
...  

2014 ◽  
Vol 6 (3) ◽  
pp. 74 ◽  
Author(s):  
Caitlin A Schonewolf ◽  
Monal Mehta ◽  
Devora Schiff ◽  
Hao Wu ◽  
Bruce G Haffty ◽  
...  

2018 ◽  
Vol 9 ◽  
pp. 36-37
Author(s):  
Kobra Hajizadeh ◽  
Bahram Behzad ◽  
Danial Seifi ◽  
Hassan Mehdian ◽  
Mohammad Nabiouni ◽  
...  

2020 ◽  

Objectives: This study aimed to investigate the potential function of miR-214 in the apoptosis induction by targeting p53 in human colorectal cancer cells (CRC) in combination with doxorubicin (DOX). Methods: miR-214 mimics were transfected to HT-29 CRC cells. Following that, the transfected cells were treated with DOX. Cell viability, apoptosis, and migration were evaluated by MTT, flow cytometry, and scratch-wound motility assays, respectively. Furthermore, the expression level of miR-214 and p53 was evaluated by qRT-PCR. Results: miR-214 transfection significantly inhibited the cell proliferation rate (P<0.05), induced apoptosis (P<0.05), and harnessed migration (P<0.05) in the HT-29 cells after 48 h. Furthermore, more effectiveness was observed in combination with DOX. Additionally, miR-214 transfection led to a reduction in p53 expression offering that it might be a potential target for miR-214. Conclusion: In conclusion, miR-214 sensitizes HT-29 cells to doxorubicin by targeting p53 indicating the significant role of this miRNA in colorectal cancer chemotherapy.


2019 ◽  
Vol 12 (2) ◽  
pp. 629-638
Author(s):  
N. N. Bahari ◽  
S. Y. N. Jamaludin ◽  
A. H. Jahidin ◽  
M. N. Zahary ◽  
A. B. Mohd Hilmi

The transient receptor potential vanilloid member 4 (TRPV4) is a non-selective calcium (Ca2+)-permeable channel which is widely expressed in different types of tissues including the lungs, liver, kidneys and salivary gland. TRPV4 has been shown to serve as a cellular sensor where it is involved in processes such as osmoregulation, cell volume regulation and thermoregulation. Emerging evidence suggests that TRPV4 also plays important roles in several aspects of cancer progression. Despite the reported roles of TRPV4 in several forms of cancers, the role of TRPV4 in human colorectal cancer remains largely unexplored. In the present study, we sought to establish the potential role of TRPV4 in colorectal cancer by assessing TRPV4 expression levels and investigating whether TRPV4 pharmacological modulation may alter cell proliferation, cell cycle and cell death in colorectal cancer cells. Quantitative real-time PCR analysis revealed that TRPV4 mRNA levels were significantly lower in HT-29 cells than normal colon CCD-18Co cells. However, TRPV4 mRNA was absent in HCT-116 cells. Pharmacological activation of TRPV4 with GSK1016790A significantly enhanced the proliferation of HT-29 cells while TRPV4 inhibition using RN 1734 decreased their proliferation. Increased proliferation in GSK1016790A-treated HT-29 cells was attenuated by co-treatment with RN 1734. Pharmacological modulation of TRPV4 had no effect on the cell cycle progression but promoted cell death in HT-29 cells. Taken together, these findings suggest differential TRPV4 expression levels in human colorectal cancer cells and that pharmacological modulation of TRPV4 produces distinct effects on the proliferation and induces cell death in HT-29 cells.


2019 ◽  
Author(s):  
JIachi Ma ◽  
Shoukai Zhang ◽  
Danru Liang ◽  
Lei Li ◽  
Jun Du ◽  
...  

Abstract Background: To better explore the underlying mechanism of liver metastatic formation by placenta-specific protein 1 (PLAC1) in human colorectal cancer, we investigated the proliferation, invasion and angiogenic capabilities of human colorectal cancer cell lines with different liver metastatic potentials as well as the mechanism of action of PLAC1 in the metastatic process. Methods: The expression of PLAC1 was detected by reverse transcriptase PCR, western blot and real-time PCR. The effect of PLAC1 on metastatic potential was determined by proliferation, invasion, and angiogenesis assays, including an in vitro coculture system consisting of cancer cells and vascular endothelial cells that were used to detect the relationship between cancer cells and angiogenesis. In addition, we also determined PLAC1 downstream targets that preferentially contribute to the metastatic process. Results: PLAC1 was expressed in HT-29, WiDr and CaCo-2 colorectal cancer cells but not in Colo320 colorectal cancer cells. PLAC1 could not only significantly enhance the proliferation of CoLo320 and human umbilical vein endothelial cells (HUVECs) but could also promote the invasion of CoLo320 cells. The angiogenesis of HUVECs was enhanced by PLAC1 in a dose-dependent manner. In cocultured systems, angiogenesis was significantly increased by coculture with HT-29 cells. In addition, PLAC1 could promote angiogenesis in coculture with HT-29 cells. Furthermore, PLAC1-enhanced metastatic potential of colorectal cancer cells was dependent on activation of the PI3K/Akt/NF-κB pathway. Conclusions: The activation of PI3K/Akt/NF-κB signaling by PLAC1 may be critical for the metastasis of colorectal cancer cells. According to our results, we suggest that modification of PLAC1 function might be a promising new therapeutic approach to inhibit the aggressive spread of colorectal cancer.


Nanomaterials ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2154
Author(s):  
Meysam Khosravifarsani ◽  
Samia Ait-Mohand ◽  
Benoit Paquette ◽  
Léon Sanche ◽  
Brigitte Guérin

Maximum benefits of chemoradiation therapy with platinum-based compounds are expected if the radiation and the drug are localized simultaneously in cancer cells. To optimize this concomitant effect, we developed the novel chemoradiotherapeutic agent [64Cu]Cu-NOTA-C3-TP by conjugating, via a short flexible alkyl chain spacer (C3), a terpyridine platinum (TP) moiety to a NOTA chelator complexed with copper-64 (64Cu). The decay of 64Cu produces numerous low-energy electrons, enabling the 64Cu-conjugate to deliver radiation energy close to TP, which intercalates into G-quadruplex DNA. Accordingly, the in vitro internalization kinetic and the cytotoxic activity of [64Cu]Cu-NOTA-C3-TP and its derivatives were investigated with colorectal cancer (HCT116) and normal human fibroblast (GM05757) cells. Radiolabeling by 64Cu results in a >55,000-fold increase of cytotoxic potential relative to [NatCu]Cu-NOTA-C3-TP at 72 h post administration, indicating a large additive effect between 64Cu and the TP drug. The internalization and nucleus accumulation of [64Cu]Cu-NOTA-C3-TP in the HCT116 cells were, respectively, 3.1 and 6.0 times higher than that for GM05757 normal human fibroblasts, which is supportive of the higher efficiency of the [64Cu]Cu-NOTA-C3-TP for HCT116 cancer cells. This work presents the first proof-of-concept study showing the potential use of the [64Cu]Cu-NOTA-C3-TP conjugate as a targeted chemoradiotherapeutic agent to treat colorectal cancer.


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