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Enhancing the Anticancer Activity of Antrodia cinnamomea in Hepatocellular Carcinoma Cells via Cocultivation With Ginger: The Impact on Cancer Cell Survival Pathways.

ABSTRACT: Antrodia cinnamomea (AC) is a medicinal fungal species that has been widely used traditionally in Taiwan for the treatment of diverse health-related conditions including cancer. It possesses potent anti-inflammatory and antioxidant properties in addition to its ability to promote cancer cell death in several human tumors. Our aim was to improve the anticancer activity of AC in hepatocellular carcinoma (HCC) through its cocultivation with ginger aiming at tuning the active ingredients. HCC cell lines, Huh-7 and HepG2 were used to study the in vitro anticancer activity of the ethanolic extracts of AC (EAC) alone or after the cocultivation in presence of ginger (EACG). The results indicated that the cocultivation of AC with ginger significantly induced the production of important triterpenoids and EACG was significantly more potent than EAC in targeting HCC cell lines. EACG effectively inhibited cancer cells growth via the induction of cell cycle arrest at G2/M phase and induction of apoptosis in Huh-7 and HepG2 cells as indicated by MTT assay, cell cycle analysis, Annexin V assay, and the activation of caspase-3. In addition, EACG modulated cyclin proteins expression and mitogen-activated protein kinase (MAPK) signaling pathways in favor of the inhibition of cancer cell survival. Taken together, the current study highlights an evidence that EACG is superior to EAC in targeting cancer cell survival and inducing apoptotic cell death in HCC. These findings support that EACG formula can serve as a potential candidate for HCC adjuvant therapy.

SUBMITTER: Chen SY

PROVIDER: S-EPMC6058215 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Enhancing the Anticancer Activity of Antrodia cinnamomea in Hepatocellular Carcinoma Cells via Cocultivation With Ginger: The Impact on Cancer Cell Survival Pathways.

Chen San-Yuan SY Lee Ying-Ray YR Hsieh Ming-Chia MC Omar Hany A HA Teng Yen-Ni YN Lin Ching-Yen CY Hung Jui-Hsiang JH

Frontiers in pharmacology 20180718

Antrodia cinnamomea (AC) is a medicinal fungal species that has been widely used traditionally in Taiwan for the treatment of diverse health-related conditions including cancer. It possesses potent anti-inflammatory and antioxidant properties in addition to its ability to promote cancer cell death in several human tumors. Our aim was to improve the anticancer activity of AC in hepatocellular carcinoma (HCC) through its cocultivation with ginger aiming at tuning the active in ...[more]

PMID: 30072899

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Project description:Introduction: Antrodia cinnamomea (AC) is an extremely rare medicinal fungus native to forested regions of Taiwan. It possesses numerous biological activities, especially anti-tumor effects shown in various in vitro cancer cells and in vivo animal models. However, there are few clinical reports about AC as a treatment for cancer patients. This report attempts to demonstrate the therapeutic effect of dish-cultured AC (DAC) on a small cell lung cancer (SCLC) patient taken orally for an extended duration. Patient concerns: An 88-year-old male with a history of diabetes mellitus and hypertension visited the outpatient department with the symptoms of dyspnea and a cough for two weeks. After a diagnosis of SCLC, the patient declined both chemotherapy and radiotherapy because of the side effects and only accepted supportive care without additional therapy. Diagnosis: Limited-stage SCLC (T4N2M1a, stage IV) after the chest radiograph, computed tomography-guided biopsy, and pathological diagnosis. Interventions: The patient was prescribed DAC with an increasing dosage, from 5 g/d up to 10 g/d DAC, for six months, without radiation or chemotherapy treatment. Outcomes: DAC caused the tumor to shrink substantially. Surprisingly, the patient survived for 32 months without relapse after six months of DAC treatment. Laboratory examinations indicated that the patient's health had improved significantly, reverting to near normal levels. Notably, he had a good quality of life with a high Barthel index score. Unfortunately, this patient died of septic shock caused by acute cholangitis. Conclusion: DAC may exert an anti-cancer effect, which can lead to tumor regression. This is supposed to be achieved by the combined DAC's immunomodulatory, anti-angiogenic, anti-metastatic, anti-proliferative, and pro-apoptotic effects mediated through multiple signaling pathways. We propose that DAC can be used as a complementary medicine to prolong the life expectancy and improve the life quality of SCLC patients.

Project description:OBJECTIVE:This study was conducted to fathom the underlying mechanisms of nutrition intervention and redox sensitive transcription factors regulated by Antrodia cinnamomea fermented product (FAC) dietary supplementation in broiler chickens. METHODS:Four hundreds d-old broilers (41±0.5 g/bird) assigned to 5 groups were examined after consuming control diet, or control diet replaced with 5% wheat bran (WB), 10% WB, 5% FAC, and 10% FAC. Liver mRNA expression of antioxidant, inflammatory and lipid metabolism pathways were analyzed. Prostaglandin E2 (PGE2) concentration in each group were tested in the chicken peripheral blood mononuclear cells (cPBMCs) of 35-d old broilers to represent the stress level of the chickens. Furthermore, these cells were stimulated with 2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH) and lipopolysaccharide (LPS) to evaluate the cell stress tolerance by measuring cell viability and oxidative species. RESULTS:Heme oxygenase-1, glutathione S-transferase, glutamate-cysteine ligase, catalytic subunit, and superoxide dismutase, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) that regulates the above antioxidant genes were all up-regulated significantly in FAC groups. Reactive oxygen species modulator protein 1 and NADPH oxygenase 1 were both rather down-regulated in 10% FAC group as comparison with two WB groups. Despite expressing higher level than control group, birds receiving diet containing FAC had significantly lower expression level in nuclear factor-kappa B (NF-κB) and other genes (inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-1β, nucleotide-binding domain, leucine-richcontaining family, pyrin domain-containing-3, and cyclooxygenase 2) involving in inflammatory pathways. Additionally, except for 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase that showed relatively higher in both groups, the WB, lipoprotein lipase, Acetyl-CoA carboxylase, fatty acid synthase, fatty acid binding protein, fatty acid desaturase 2 and peroxisome proliferator-activated receptor alpha genes were expressed at higher levels in 10% FAC group. In support of above results, promoted Nrf2 and inhibited NF-κB nuclear translocation in chicken liver were found in FAC containing groups. H2O2 and NO levels induced by LPS and AAPH in cPBMCs were compromised in FAC containing diet. In 35-d-old birds, PGE2 production in cPBMCs was also suppressed by the FAC diet. CONCLUSION:FAC may promote Nrf2 antioxidant pathway and positively regulate lipid metabolism, both are potential inhibitor of NF-κB inflammatory pathway.

Dataset Information

Enhancing the Anticancer Activity of Antrodia cinnamomea in Hepatocellular Carcinoma Cells via Cocultivation With Ginger: The Impact on Cancer Cell Survival Pathways.

Publications

Enhancing the Anticancer Activity of <i>Antrodia cinnamomea</i> in Hepatocellular Carcinoma Cells via Cocultivation With Ginger: The Impact on Cancer Cell Survival Pathways.

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