Long non-coding RNA H19 is aberrantly expressed in multiple malignancies and its expression levels correlate with recurrence, metastasis, and patient survival. Despite numerous reports documenting ...the role of H19 in carcinogenesis, its contribution to cervical cancer development is still largely unknown. In this study, I observed that H19 expression was elevated in cervical cancer cell lines and could be detected in extracellular vesicles in the culture medium. In addition, I demonstrated, by overexpression and knockdown experiments, that H19 promoted cell proliferation and multicellular tumor spheroid formation without significantly affecting apoptosis and cell migration. Finally, treatment with transforming growth factor beta and hypoxia-mimetic CoCl2 could modulate H19 levels in a cell line-specific manner. These findings indicate that H19 promotes both anchorage-specific and -independent growth of cervical cancer cell lines and may serve as a potential target for cancer diagnosis and therapy.
Background
Sea holly has long been used in traditional Thai medicine for longevity, skin inflammation, skin dullness and as a treatment for itchy skin. The white flower cultivar
Acanthus ebracteatus
...Vahl. has been documented to perform better remedies than the purple flower
A. ilicifolius
. Nonetheless, preparation of the phenolic-rich extract of
A. ebracteatus
, including safety and cellular assessments relevant for inflammation and aging treatment is sparingly presented. In this study, the extracts of
A. ebracteatus
were prepared and comparatively quantified on total phenolic contents. In vitro activities by means of ABTS, DPPH, FRAP and mushroom tyrosinase inhibitory assays were undertaken. The extracts were UPLC analyzed and examined on cellular safety and activities.
Results
The phenolic-rich extracts of
A. ebracteatus
were prepared and standardized in verbascoside. The extracts were noted to have in vitro antioxidant and anti-tyrosinase activities. Cellular activities, co-cultures and ex vivo human skin appointed for cutaneous aging treatment, i.e., photoaging, are promising including antioxidant, anti-melanogenesis, anti-inflammatory (IL-6 and IL-8), anti-MMP and collagen production stimulating as well as anti-senescence activities.
Conclusions
Sea holly is highlighted as a potential source for beneficial cutaneous phenolics, especially verbascoside. The extracts were proven to be safe and efficient for cutaneous aging treatment indicated by their antioxidant, anti-melanogenesis, collagen stimulating, anti-inflame and anti-senescence activities. The plant extracts are therefore appointed for use as innovative agents for anti-aging purposes.
Graphical Abstract
Skin aging is accompanied by an increase in the number of senescent cells, resulting in various pathological outcomes. These include inflammation, impaired barrier function, and susceptibility to ...skin disorders such as cancer. Kaempferia parviflora (Thai black ginger), a medicinal plant native to Thailand, has been shown to counteract inflammation, cancer, and senescence. This study demonstrates that polymethoxyflavones (5,7-dimethoxyflavone, 5,7,4′-trimethoxyflavone, and 3,5,7,3′,4′-pentamethoxyflavone) purified from K. parviflora rhizomes suppressed cellular senescence, reactive oxygen species, and the senescence-associated secretory phenotype in primary human dermal fibroblasts. In addition, they increased tropocollagen synthesis and alleviated free radical-induced cellular and mitochondrial damage. Moreover, the compounds mitigated chronological aging in a human ex vivo skin model by attenuating senescence and restoring expression of essential components of the extracellular matrix, including collagen type I, fibrillin-1, and hyaluronic acid. Finally, we report that polymethoxyflavones enhanced epidermal thickness and epidermal-dermal stability, while blocking age-related inflammation in skin explants. Our findings support the use of polymethoxyflavones from K. parviflora as natural anti-aging agents, highlighting their potential as active ingredients in cosmeceutical and nutraceutical products.
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•Three polymethoxyflavones (DMF, TMF, and PMF) were purified from Kaempferia parviflora rhizomes.•Polymethoxyflavones alleviated cellular senescence and mitochondrial dysfunction in primary human dermal fibroblasts.•Polymethoxyflavones rejuvenated chronological aging in human ex vivo skin.
When confronted with poor oxygenation, cells adapt by activating survival signaling pathways, including the oxygen-sensitive transcriptional regulators called hypoxia-inducible factor alphas ...(HIF-αs). We report here that HIF-1α also regulates the life cycle of Epstein-Barr virus (EBV). Incubation of EBV-positive gastric carcinoma AGS-Akata and SNU-719 and Burkitt lymphoma Sal and KemIII cell lines with a prolyl hydroxylase inhibitor, L-mimosine or deferoxamine, or the NEDDylation inhibitor MLN4924 promoted rapid and sustained accumulation of both HIF-1α and lytic EBV antigens. ShRNA knockdown of HIF-1α significantly reduced deferoxamine-mediated lytic reactivation. HIF-1α directly bound the promoter of the EBV primary latent-lytic switch BZLF1 gene, Zp, activating transcription via a consensus hypoxia-response element (HRE) located at nt -83 through -76 relative to the transcription initiation site. HIF-1α did not activate transcription from the other EBV immediate-early gene, BRLF1. Importantly, expression of HIF-1α induced EBV lytic-gene expression in cells harboring wild-type EBV, but not in cells infected with variants containing base-pair substitution mutations within this HRE. Human oral keratinocyte (NOK) and gingival epithelial (hGET) cells induced to differentiate by incubation with either methyl cellulose or growth in organotypic culture accumulated both HIF-1α and Blimp-1α, another cellular factor implicated in lytic reactivation. HIF-1α activity also accumulated along with Blimp-1α during B-cell differentiation into plasma cells. Furthermore, most BZLF1-expressing cells observed in lymphomas induced by EBV in NSG mice with a humanized immune system were located distal to blood vessels in hypoxic regions of the tumors. Thus, we conclude that HIF-1α plays central roles in both EBV's natural life cycle and EBV-associated tumorigenesis. We propose that drugs that induce HIF-1α protein accumulation are good candidates for development of a lytic-induction therapy for treating some EBV-associated malignancies.
is a perennial herb widely distributed in many warmer regions, including Thailand, and is well-known for its medicinal and ornamental values. Crinum alkaloids contain numerous compounds, such as ...crinamine. Even though its mechanism of action is still unknown, crinamine was previously shown to possess anticancer activity. In this study, we demonstrate that crinamine was more cytotoxic to cervical cancer cells than normal cells. It also inhibited anchorage-independent tumor spheroid growth more effectively than existing chemotherapeutic drugs carboplatin and 5-fluorouracil or the CDK9 inhibitor FIT-039. Additionally, unlike cisplatin, crinamine induced apoptosis without promoting DNA double-strand breaks. It suppressed cervical cancer cell migration by inhibiting the expression of positive regulators of epithelial-mesenchymal transition SNAI1 and VIM. Importantly, crinamine also exerted anti-angiogenic activities by inhibiting secretion of VEGF-A protein in cervical cancer cells and blood vessel development in zebrafish embryos. Gene expression analysis revealed that its mechanism of action might be attributed, in part, to downregulation of cancer-related genes, such as AKT1, BCL2L1, CCND1, CDK4, PLK1, and RHOA. Our findings provide a first insight into crinamine's anticancer activity, highlighting its potential use as an alternative bioactive compound for cervical cancer chemoprevention and therapy.
Lion’s Mane mushroom (
Hericium erinaceus
), LM, is a medicinal mushroom which has various bioactive compounds within its fruiting bodies. However, during the cultivation, a large amount of the ...irregular-shape LM (Ir-LM) was generated. This mushroom type was considered a mushroom by-product. In this study, conventional solvent extraction (Maceration) and supercritical fluid extraction using carbon dioxide (SCFE-CO
2
) were performed to compare the recovery of ergosterol, hericenone C, and hericene A content from Reg-LM and Ir-LM fruiting bodies. Furthermore, two extraction conditions (40°C at 200 bar and 70°C at 350 bar) were conducted for the SCFE-CO
2
technique. The results showed that SCFE-CO
2
methods produced a higher recovery of ergosterol and hericenone C as compared to the Maceration techniques. SCFE-CO
2
extracts were determined for their antioxidant activities. The DPPH radical scavenging activity of the extract from 70°C at 350 bar was significantly higher (p < 0.05) than the extract obtained from 40°C at 200 bar. The results revealed the use of green technology supercritical fluid extraction using carbon dioxide to recover bioactive compounds from mushroom by-products and apply for high-value added products.
Lion’s Mane mushroom (
Hericium erinaceus
) is one of the most popularly edible and medicinal mushrooms. However, there is still a lack of knowledge on the relationship between growth period and ...bioactive content in the mushroom. The objectives of this research were to study bioactive compounds and antioxidant activity of Lion’s Mane mushroom at various growth periods. The mushroom was cultivated and harvested at growth periods of 14, 21, and 28-days. The samples were dried by lyophilization and extracted with ethanol. Bioactive compounds (ergosterol, hericenone C, and hericene A), total phenolic content, total flavonoid content, and antioxidant activity of the samples were analyzed. HPLC analysis demonstrated the highest concentration of ergosterol, hericenone C and hericene A in the 14-days, 21-days, and 28-days samples, respectively. Total phenolic content and total flavonoid content of the dried sample were not statistically significant different (p>0.05). The 21-days sample showed higher activity than the 14-days and 28-days samples for both DPPH and ABTS radical scavenging assays. In conclusion, the 14-days sample showed the highest concentrations of bioactive compounds, while the 21-days sample showed the highest yield and antioxidant activity. The 28-days sample exhibited a change in morphology and color. This study demonstrates that the growth periods of Lion’s Mane mushroom play a role in their bioactive compounds and antioxidant activities. Finally, the correlation of growth periods to the content of other bioactive compounds can be used for mushroom cultivation and applications in foods, food supplements and cosmetics.