Investigation of apoptotic effect of juglone on CCL-228-SW 480 colon cancer cell line

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Date: January-March 2019
Publisher: Medknow Publications and Media Pvt. Ltd.
Document Type: Report
Length: 3,993 words
Lexile Measure: 1670L

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Byline: Dilek. Bayram, Meltem. Ozgocmen, Ilkay. Armagan, Murat. Sevimli, Gulcin. Turel, Nurgul. ?enol

Background: Colon cancer is a major cause of morbidity and mortality in the world. Juglone is a natural compound which has been isolated from Juglans mandshurica Maxim, and it has various pharmacological effects such as antiviral, antibacterial, and anticancer. In our study, we aimed to investigate the effect of juglone on CCL-228-SW 480 colon carcinoma cell line in monolayer and spheroid culture medium. Materials and Methods: The CCL-228-SW 480 cell lines were cultured in both monolayer and spheroid cultures. Cells were treated with juglone at 24, 48, and 72 h of incubation. ID50 inhibition was determined on the dose for juglone and after it was found 20 [micro]M was applied to the cells to examine the effect of juglone on CCL-228-SW 480 colon carcinoma cell line. After Juglone was applied the BrdU marking index, Transferase dUTP Nick ends Labeling (TUNEL) assay, active caspase-3 assay, apoptosis-inducing factor (AIF) assay were determined by immunohistochemistry in both the monolayer and spheroid cultures. Results: The control group had a healthy pattern of S-phase fraction, and many of the CCL-228-SW 480 cells nuclei were observed to be positive for BrdU. Terminal Deoxynucleotidyl TUNEL-positive cells, active Caspase-3, and AIF were detected after treatment with juglone in both the monolayer and spheroid cultures. Conclusions: The dead cell count was higher in the CCL-228-SW 480 cell lines with juglone applied than in the controls. Juglone significantly inhibits the proliferation and induces the apoptosis of CCL-228-SW 480 cells in vitro.


Colon cancer is the third most commonly diagnosed cancer and the fourth leading cause of cancer-related death globally.[1] The most efficient therapy for colon cancer is surgery combined with radiotherapy, immunotherapy, chemotherapy, or traditional Chinese herbal medicine. However, side effects can be severe for both radiotherapy and chemotherapy and the survival rate remains low because of the reoccurrence and migration of colon tumors. Thus, finding an appropriate way to improve therapeutic efficiency without side effects is crucial.[2]

Quinones are common secondary metabolic products that possess a variety of pharmacological properties, such as antibacterial, antifungal, antioxidant, anti-inflammatory, and anticancer activity.[3] Juglone (5-hydroxy-1,4-naphthoquinone) is a natural 1,4-naphthoquinone found in the Juglandaceae family, particularly in the roots, leaves, bark, and wood of Juglans regia [Figure 1]. Juglone has shown cytotoxic effects against various tumor cells and also has antifungal, antibacterial, and antiviral activities, as well as allelopathic activities.[4],[5],[6],[7],[8] Although juglone should be a promising agent for oncotherapy, its clinical applications have been limited due to its poor solubility in aqueous solutions, poor absorption, and generalized cytotoxicity to normal tissues.[9]{Figure 1}

Apoptosis occurs normally during development and aging and as a homeostatic mechanism to maintain cell populations in tissues. Apoptosis also occurs as a defense mechanism such as in immune reactions or when cells are damaged by disease or noxious agents.[10] The irradiation and drugs used in cancer chemotherapy result in DNA damage in some cells, which can lead to apoptotic death through a p53-dependent pathway.[11]

In the present...

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Gale Document Number: GALE|A578873939