Effects of Polar Steroids from the Starfish Patiria (=Asterina) pectinifera in Combination with X-Ray Radiation on Colony Formation and Apoptosis Induction of Human Colorectal Carcinoma Cells

Despite significant advances in the understanding, prevention, and treatment of cancer, the disease continues to affect millions of people worldwide. Chemoradiation therapy is a rational approach that has already proven beneficial for several malignancies. However, the existence of toxicity to normal tissue is a serious limitation of this treatment modality. The aim of the present study is to investigate the ability of polar steroids from starfish Patiria (=Asterina) pectinifera to enhance the efficacy of radiation therapy in colorectal carcinoma cells. The cytotoxic activity of polar steroids and X-ray radiation against DLD-1, HCT 116, and HT-29 cells was determined by an MTS assay. The effect of compounds, X-ray, and their combination on colony formation was studied using the soft agar method. The molecular mechanism of the radiosensitizing activity of asterosaponin P1 was elucidated by western blotting and the DNA comet assay. Polar steroids inhibited colony formation in the tested cells, and to a greater extent in HT-29 cells. Asterosaponin P1 enhanced the efficacy of radiation and, as a result, reduced the number and size of the colonies of colorectal cancer cells. The radiosensitizing activity of asterosaponin P1 was realized by apoptosis induction through the regulation of anti- and pro-apoptotic protein expression followed by caspase activation and DNA degradation.

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Modulation of Cyclooxygenase-2 Expression by Apc In Ht-29 Human Colorectal Carcinoma Cells

Advances in Experimental Medicine and Biology - Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 5 ◽

10.1007/978-1-4615-0193-0_21 ◽

2002 ◽

pp. 127-131 ◽

Cited By ~ 1

Author(s):

Linda C. Hsi ◽

Julie Angerman-Stewart ◽

Thomas E. Eling

Keyword(s):

Colorectal Carcinoma ◽

Cyclooxygenase 2 ◽

Carcinoma Cells ◽

Human Colorectal Carcinoma ◽

Ht 29

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High Concentrations of Aspartame Induce Pro-Angiogenic Effects in Ovo and Cytotoxic Effects in HT-29 Human Colorectal Carcinoma Cells

Nutrients ◽

10.3390/nu12123600 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3600 ◽

Cited By ~ 1

Author(s):

Anca Laura Maghiari ◽

Dorina Coricovac ◽

Iulia Andreea Pinzaru ◽

Ioana Gabriela Macașoi ◽

Iasmina Marcovici ◽

...

Keyword(s):

Colorectal Cancer ◽

Colorectal Carcinoma ◽

In Vitro Cytotoxicity ◽

Scientific Data ◽

Carcinoma Cells ◽

Artificial Sweetener ◽

In Ovo ◽

Human Colorectal Carcinoma ◽

Ht 29

Aspartame (ASP), an artificial sweetener abundantly consumed in recent years in an array of dietary products, has raised some concerns in terms of toxicity, and it was even suggested a link with the risk of carcinogenesis (colorectal cancer), though the present scientific data are rather inconclusive. This study aims at investigating the potential role of aspartame in colorectal cancer by suggesting two experimental approaches: (i) an in vitro cytotoxicity screening in HT-29 human colorectal carcinoma cells based on cell viability (Alamar blue assay), cell morphology and cell migration (scratch assay) assessment and (ii) an in ovo evaluation in terms of angiogenic and irritant potential by means of the chorioallantoic membrane method (CAM). The in vitro results showed a dose-dependent cytotoxic effect, with a significant decrease of viable cells at the highest concentrations tested (15, 30 and 50 mM) and morphological cellular changes. In ovo, aspartame (15 and 30 mM) proved to have a pro-angiogenic effect and a weak irritant potential at the vascular level. These data suggest new directions of research regarding aspartame’s role in colorectal cancer.

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Introduction of full-length APC modulates cyclooxygenase-2 expression in HT-29 human colorectal carcinoma cells at the translational level

Prostaglandins & Other Lipid Mediators ◽

10.1016/s0090-6980(99)90401-x ◽

1999 ◽

Vol 59 (1-6) ◽

pp. 166

Author(s):

Linda C. Hsi ◽

Julie Angerman-Stewart ◽

Thomas E. Eling

Keyword(s):

Colorectal Carcinoma ◽

Cyclooxygenase 2 ◽

Carcinoma Cells ◽

Full Length ◽

Human Colorectal Carcinoma ◽

Ht 29 ◽

Translational Level

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TRAP1, a novel antiapoptotic gene responsible for multidrug resistance in human colorectal carcinoma cells

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.2541 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 2541-2541

Author(s):

M. Landriscina ◽

E. Costantino ◽

F. Maddalena ◽

A. Piscazzi ◽

A. Fersini ◽

...

Keyword(s):

Colorectal Cancer ◽

Multidrug Resistance ◽

Colorectal Carcinoma ◽

Carcinoma Cells ◽

Dominant Negative ◽

Multi Drug Resistance ◽

Colorectal Carcinomas ◽

Osteosarcoma Cells ◽

Tumor Cell Death ◽

Ht 29

2541 Background: TRAP1 has been recently described as a component of a mitochondrial pathway selectively up- regulated in tumor cells which antagonizes the proapoptotic activity of cyclophilin D and is responsible for maintenance of mitochondria integrity, thus favoring cell survival. Interestingly, novel TRAP1 antagonists cause sudden collapse of mitochondrial function and selective tumor cell death, suggesting that this pathway may represent a novel molecular target to improve anticancer therapy. Furthermore, we recently observed that TRAP1 is significantly up-regulated in osteosarcoma cells adapted to growth in mild oxidizing conditions and this correlates with a phenotype more resistant to H2O2-induced DNA damage and apoptosis. This evidence prompted us to investigate the role of TRAP1 as being responsible for multi-drug resistance in human colorectal cancer. Methods and Results: The evaluation of TRAP1 expression by immunoblot and quantitative RT-PCR analysis in a series of 26 human colorectal carcinomas allowed us to observe up-regulation in 17/26 tumors. Accordingly, TRAP1 protein levels were increased in HT-29 colorectal carcinoma cells resistant to 5-fluorouracil, oxaliplatin and irinotecan. Interestingly, HT-29 colorectal carcinoma and Saos-2 osteosarcoma cells transfected with TRAP1 gene exhibited a phenotype resistant to 5-fluorouracil-, oxaliplatin- and irinotecan-induced apoptosis, evaluated by MTT incorporation analysis and annexin V staining. Consistently, the transfection of a dominant negative N-terminal deletion mutant of TRAP1 as well as the inhibition of TRAP1 activity by the TRAP1 ATPase antagonist, shepherdin, increased the sensitivity to apoptosis induced by 5-fluorouracil, oxaliplatin and irinotecan in wild type HT-29 colorectal carcinoma cells and in HT-29 cells resistant to the single agents. Conclusions: These results suggest that the increased expression of TRAP1 in human colorectal carcinomas could be part of a pro-survival pathway responsible for multidrug resistance. Thus, targeting TRAP1 may represent a novel strategy to improve the efficacy of anticancer agents in colorectal cancer. No significant financial relationships to disclose.

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Aqueous Extract ofSolanum nigrumLeaves Induces Autophagy and Enhances Cytotoxicity of Cisplatin, Doxorubicin, Docetaxel, and 5-Fluorouracil in Human Colorectal Carcinoma Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/514719 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 13

Author(s):

Chen-Jei Tai ◽

Chien-Kai Wang ◽

Cheng-Jeng Tai ◽

Yi-Feng Lin ◽

Chi-Shian Lin ◽

...

Keyword(s):

Colorectal Cancer ◽

Colorectal Carcinoma ◽

Aqueous Extract ◽

Tumor Suppression ◽

Drug Effect ◽

Carcinoma Cells ◽

Common Cancer ◽

Human Colorectal Carcinoma ◽

And Control ◽

Ht 29

Colorectal cancer is a common cancer worldwide, and chemotherapy is a mainstream approach for advanced and recurrent cases. Development of effective complementary drugs could help improve tumor suppression efficiency and control adverse effects from chemotherapy. The aqueous extract ofSolanum nigrumleaves (AE-SN) is an essential component in many traditional Chinese medicine formulas for treating cancer, but there is a lack of evidence verifying its tumor suppression efficacy in colorectal cancer. The purpose of this study is to evaluate the tumor suppression efficacy of AE-SN using DLD-1 and HT-29 human colorectal carcinoma cells and examine the combined drug effect when combined with the chemotherapeutic drugs cisplatin, doxorubicin, docetaxel, and 5-fluorouracil. The results indicated that AE-SN induced autophagy via microtubule-associated protein 1 light chain 3 A/B II accumulation but not caspase-3-dependent apoptosis in both cell lines. The IC50s after 48 hours of treatment were 0.541 and 0.948 mg/ml AE-SN in DLD-1 and HT-29, respectively. AE-SN also demonstrated a combined drug effect with all tested drugs by enhancing cytotoxicity in tumor cells. Our results suggest that AE-SN has potential in the development of complementary chemotherapy for colorectal cancer.

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Cytotoxic Effects of Cannabinoids on Human HT-29 Colorectal Adenocarcinoma Cells: Different Mechanisms of THC, CBD, and CB83

International Journal of Molecular Sciences ◽

10.3390/ijms21155533 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5533 ◽

Cited By ~ 1

Author(s):

Daniela Cerretani ◽

Giulia Collodel ◽

Antonella Brizzi ◽

Anna Ida Fiaschi ◽

Andrea Menchiari ◽

...

Keyword(s):

Colorectal Carcinoma ◽

Cell Viability ◽

Annexin V ◽

Ascorbic Acid Content ◽

Carcinoma Cells ◽

Cytotoxic Effects ◽

Adenocarcinoma Cells ◽

Malondialdehyde Content ◽

Ht 29 ◽

In Cells

In this study, we investigated the effects of exposition to IC50 dose for 24 h of a new synthetic cannabinoid (CB83) and of phytocannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on HT-29 colorectal carcinoma cells. Cell viability and proliferative activity evaluated using the MTT, lactate dehydrogenase (LDH), and CyQUANT assays showed that cell viability was significantly affected when CB83, THC, and CBD were administered to cells. The results obtained showed that the reduced glutathione/oxidized glutathione ratio was significantly reduced in the cells exposed to CBD and significantly increased in the cells treated with the CB83 when compared to the controls. CBD treatment causes a significant increase in malondialdehyde content. The catalase activity was significantly reduced in HT-29 cells after incubation with CB83, THC, and CBD. The activities of glutathione reductase and glutathione peroxidase were significantly increased in cells exposed to THC and significantly decreased in those treated with CBD. The ascorbic acid content was significantly reduced in cells exposed to CB83, THC, and CBD. The ultrastructural investigation by TEM highlighted a significantly increased percentage of cells apoptotic and necrotic after CB83 exposition. The Annexin V-Propidium Iodide assay showed a significantly increased percentage of cells apoptotic after CB83 exposition and necrotic cells after CBD and THC exposition. Our results proved that only CBD induced oxidative stress in HT-29 colorectal carcinoma cells via CB receptor-independent mechanisms and that CB83 caused a mainly CB2 receptor-mediated antiproliferative effect comparable to 5-Fuorouracil, which is still the mainstay drug in protocols for colorectal cancer.

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