Galangin: A Promising Flavonoid for the Treatment of Rheumatoid Arthritis-Mechanisms, Evidence, and Therapeutic Potential.

Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by progressive joint inflammation and damage. Oxidative stress plays a critical role in the onset and progression of RA, significantly contributing to the disease's symptoms. The complex nature of RA and the role of oxidative stress make it particularly challenging to treat effectively. This article presents a comprehensive review of RA's development, progression, and the emergence of novel treatments, introducing Galangin (GAL), a natural flavonoid compound sourced from various plants, as a promising candidate. The bioactive properties of GAL, including its anti-inflammatory, antioxidant, and immunomodulatory effects, are discussed in detail. The review elucidates GAL's mechanisms of action, focusing on its interactions with key targets such as inflammatory cytokines (e.g., TNF-α, IL-6), enzymes (e.g., SOD, MMPs), and signaling pathways (e.g., NF-κB, MAPK), which impact inflammatory responses, immune cell activation, and joint damage. The review also addresses the lack of comprehensive understanding of potential treatment options for RA, particularly in relation to the role of GAL as a therapeutic candidate. It highlights the need for further research and clinical studies to ascertain the effectiveness of GAL in RA treatment and to elucidate its mechanisms of action. Overall, this review provides valuable insights into the potential of GAL as a therapeutic option for RA, shedding light on its multifaceted pharmacological properties and mechanisms of action, while suggesting avenues for future research and clinical applications.

Proapoptotic and Antiproliferative Effects of the Desert Truffle Terfezia boudieri on Colon Cancer Cell Lines.

Background: Colon cancer is the second leading cause of cancer-related mortality, and ranks third among cancers in terms of prevalence. Despite advances in early detection and treatment with chemotherapy and surgery, colon cancer continues to be associated with high recurrence rates, thereby resulting in a heavy disease burden. Moreover, the effectiveness of currently available treatment modalities is limited by the occurrence of toxic side effects. Hence, there is an urgent need to develop alternative treatments. Extracts from the black desert truffle Terfezia boudieri (T. boudieri) have shown promising anticancer properties. However, the cellular mechanisms underlying this activity remain poorly understood. Methods: In this study, the colon cancer cell lines HCT-116 and Caco-2 were treated with either water or ethanolic extract of T. boudieri. Cell viability and the half-maximal inhibitory concentration were determined using MTT assays. Then, the activity of the more potent water extract was further verified using crystal violet assays, and its role in inhibiting colony formation and wound healing was investigated. Protein levels of p53, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax), cyclin D1 (CCND1), and c-Myc were measured in cells treated with different doses of the water extract. Results: Treatment with the water extract of T. boudieri reduced the capacity of cells for wound healing and colony formation in a dose-dependent manner. The Bax/Bcl-2 ratio and p53 expression were elevated in both cell lines. In contrast, the levels of cyclin D1 and c-Myc were suppressed. Conclusion: T. boudieri water extract exerted a cytotoxic effect on colon cancer cells, and blocked colony formation and wound healing potentially through inhibition of proliferation. Mechanistically, these effects are attributed to influence the mitochondrial pathway of apoptosis, proteins involved in cellular proliferation, and the cell cycle.

Gamma-Tocotrienol Synergistically Promotes the Anti-proliferative and Pro-apoptotic Effects of Etoposide on Breast Cancer Cell Lines.

BACKGROUND: Breast Cancer is one of the most commonly diagnosed cancers worldwide and a major cause of death among women. Although chemotherapeutic agents remain the keystones in cancer therapy, significant side effects have failed to provide a safe and tolerable treatment for cancer patients. Dietary antioxidant vitamins were extensively investigated over the past years and their relevance in cancer chemotherapy remains to be elucidated. OBJECTIVE: In the current study, we aimed to investigate the anti-proliferative and apoptotic effects of combining γ-tocotrienol, a member of the vitamin E family, with the chemotherapeutic drug etoposide in MCF-7 and MDA-MB-231 breast cancer cell lines. METHODS: The antiproliferative effect of etoposide combined with γ-tocotrienol was measured using MTS viability reagent. The pro-apoptotic effect was elucidated through Cell Death ELISA and dual Annexin V/PI staining followed by flow cytometric analysis. RESULTS: Our results showed that etoposide significantly decreased the cell growth of both cell lines, with MDA-MB-231 cells being more sensitive to etoposide treatment than MCF-7. Moreover, simultaneous treatment of both breast cancer cell lines with low doses of γ-tocotrienol and etoposide induced a synergistic antiproliferative effect (CI<1). Furthermore, the combination therapy significantly increased the percentage of total apoptotic cells in the MDA-MB-231 cell line and the degree of DNA fragmentation as compared to treatment with either compound alone. CONCLUSION: In conclusion, our results provide evidence for the profound anti-tumorigenic effect of combined etoposide and γ-tocotrienol in the breast cancer cell lines.

Adjuvant Epigenetic Therapy of Decitabine and Suberoylanilide Hydroxamic Acid Exerts Anti-Neoplastic Effects in Acute Myeloid Leukemia Cells.

Atypical epigenetic processes including histone acetylation and DNA methylation have been identified as a fundamental theme in hematologic malignancies. Such mechanisms modify gene expression and prompt, in part at least, the initiation and progression of several malignancies including acute myeloid leukemia. In the current study we determined the effects of treating KG-1 and U937 acute myeloid leukemia (AML) cells, in vitro, with the HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA), or with a DNMT inhibitor, decitabine (DAC), or their combination, on cell proliferation, cell cycle progression, apoptosis, and expression of apoptosis-related proteins. Each of SAHA and DAC attenuated cell proliferation and induced cell cycle arrest and apoptotic cell death of KG-1 and U937 cell lines. Besides, their sequential combination improved the obtained anti-neoplastic effect: significant augmentation of growth inhibition and apoptosis induction as compared to cells treated with either drug alone. This effect was featured by the upregulated expression of Bax, cytochrome c1, p21, and cleaved caspases 8, 9, and 3, signifying the activation of both the intrinsic and extrinsic pathways of apoptosis. The sequential combination of SAHA and DAC causes a profound antitumorigenic effect in AML cell lines by inducing the expression of tumor suppressor genes.

The Vitamin E Derivative Gamma Tocotrienol Promotes Anti-Tumor Effects in Acute Myeloid Leukemia Cell Lines.

Acute myeloid leukemia (AML) is a blood cancer characterized by the formation of faulty defective myelogenous cells with morphological heterogeneity and cytogenic aberrations leading to a loss of their function. In an attempt to find an effective and safe AML treatment, vitamin E derivatives, including tocopherols were considered as potential anti-tumor compounds. Recently, other isoforms of vitamin E, namely tocotrienols have been proposed as potential potent anti-cancerous agents, displaying promising therapeutic effects in different cancer types. In this study we evaluated the anti-cancerous effects of γ-tocotrienol, on AML cell lines in vitro. For this purpose, AML cell lines incubated with γ-tocotrienol were examined for their viability, cell cycle status, apoptotic cell death, DNA fragmentation, production of reactive oxygen species and expression of proapoptotic proteins. Our results showed that γ-tocotrienol exhibits time and dose-dependent anti-proliferative, pro-apoptotic and antioxidant effects on U937 and KG-1 cell lines, through the upregulation of proteins involved in the intrinsic apoptotic pathway.

Synergistic Effect of Epigenetic Inhibitors Decitabine and Suberoylanilide Hydroxamic Acid on Colorectal Cancer In vitro.

BACKGROUND: Colorectal Cancer (CRC) is a common cause of oncological deaths worldwide. Alterations of the epigenetic landscape constitute a well-documented hallmark of CRC phenotype. The accumulation of aberrant DNA methylation and histone acetylation plays a major role in altering gene activity and driving tumor onset, progression and metastasis. OBJECTIVE: In this study, we evaluated the effect of Suberoylanilide Hydroxamic Acid (SAHA), a panhistone deacetylase inhibitor, and Decitabine (DAC), a DNA methyltransferase inhibitor, either alone or in combination, on Caco-2 human colon cancer cell line in vitro. RESULTS: Our results showed that SAHA and DAC, separately, significantly decreased cell proliferation, induced apoptosis and cell cycle arrest of Caco-2 cell line. On the other hand, the sequential treatment of Caco-2 cells, first with DAC and then with SAHA, induced a synergistic anti-tumor effect with a significant enhancement of growth inhibition and apoptosis induction in Caco-2 cell line as compared to cells treated with either drug alone. Furthermore, the combination therapy upregulates protein expression levels of pro-apoptotic proteins Bax, p53 and cytochrome c, downregulates the expression of antiapoptotic Bcl-2 protein and increases the cleavage of procaspases 8 and 9; this suggests that the combination activates apoptosis via both the intrinsic and extrinsic pathways. Mechanistically, we demonstrated that the synergistic anti-neoplastic activity of combined SAHA and DAC involves an effect on PI3K/AKT and Wnt/ß-catenin signaling. CONCLUSION: In conclusion, our results provide evidence for the profound anti-tumorigenic effect of sequentially combined SAHA and DAC in the CRC cell line and offer new insights into the corresponding underlined molecular mechanism.