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Colorectal cancer is the third most common cancer that constitutes 50% of the total cancer-related death in the western world. People suffering from inflammatory bowel disorders like ulcerative colitis and Crohn’s diseases are more prone to colorectal cancer than others.
About 75% of the cases of colorectal cancer are nonhereditary in nature while colorectal cancers of genetic origin are due to the mutations in the multistep pathogenesis of the colorectal cancer cell-like the failure of the adenomatous polyposis coli (APC) suppressor gene function.
APC is a tumor suppressor protein composed of the proteolytic destruction complex. It regulates the Wnt signaling pathway by degrading the β-catenin, a transcriptional co-activator of the Wnt pathway. Therefore, in the absence of APC, β-catenin is stabilized and translocated into the nucleus where it binds to the LEF-1/TCF proteins and activates the Wnt target genes. Activated Wnt target genes lead to the accumulation of the transcription factors required for the cell cycle progression and cancer development.
There are many natural products available with a wide range of biological activities such as anti-inflammatory, anticancer, and antioxidant activities that can effectively be used in medicine and health. Mushrooms such as Chaga mushroom, red mushrooms are commonly used in traditional medicine for many years to treat a wide range of disorders including cancers.
Recently, researchers have found an anti-cancerous activity in the hot water extract (aqueous extract) of the Chaga mushroom that inhibits the proliferation of human colorectal cancer cells. Therefore, researchers isolated several components from the Chaga mushroom and analyzed these components against the viability and apoptosis of colon cancer cells.
Extraction of Ergosterol Peroxide from Chaga Mushroom
The researchers have analyzed the effect of ergosterol peroxide extracted from the Chaga mushroom on the human colorectal cancer cell lines and the colitis induced colorectal cancer cells developed by the Azoxymethane/Dextran Sulfate Sodium in the mouse model. Pure ergosterol peroxide was also tested for anti-proliferative and apoptosis as a control.
They found the n-hexane extract most effective against the anti-proliferative effect as compared to aqueous extract of the Chaga mushroom while the other extracts like ethanol, ethyl acetate, and n-butanol extracts were less effective. Upon further fractionation of the n-hexane extract into 15 fractions by chromatography, researchers found the 15th fraction more effectively inhibited the growth of the colorectal cancer cells. After NMR analysis, it was found that the 15th fraction contained ergosterol peroxide.
Role of Ergosterol Peroxide in Apoptosis
At last, to confirm whether the inhibition of cell proliferation observed in the colorectal cancer cell lines is due to apoptosis or not, researchers had analyzed the cell-cycle arrest and apoptosis during which they found that ergosterol peroxide-induced subG1 arrest in all the colorectal cancer cell lines.
This result confers that the ergosterol peroxide is the one that causes apoptosis in the CRC cell lines by inducing the expression of the poly (ADP-Ribose) polymerase (PARP) and caspase-3. Caspase-3 activated by the ergosterol peroxide helps to cleave the PARP leading to the cell cycle arrest and apoptosis.
The researchers also observed that ergosterol peroxide on colorectal cancer cell lines had reduced the expression of β-catenin leading to the reduced level of expression of c-Myc, cyclin D1, and CDK-8. While in the case of the AOM/DSS-induced adenocarcinoma mouse model, ergosterol peroxide treatment had caused the good preservation of the crypt structure and also improved the histological features as compared to that of the mouse model without ergosterol peroxide treatment. This revealed the ergosterol peroxide treatment doesn’t affect the tumor incident but tends to suppress the tumor growth in the colon of the AOM/DSS-treated mouse.
Ergosterol peroxide present in the Chaga mushroom can be used as a chemotherapeutic agent in the treatment of colorectal cancer where it prevents cancer cell proliferation by down-regulating the β-catenin signaling and inducing apoptotic activities in the colorectal cancer cell lines.
Reference: Journal of Ethnopharmacology
Article DOI: 10.1016/j.jep.2015.07.030