Polymethoxyflavones from Kaempferia parviflora ameliorate skin aging in primary human dermal fibroblasts and ex vivo human skin.

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.

Cleistanthin A induces apoptosis and suppresses motility of colorectal cancer cells.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Here, we investigated the molecular mechanisms that underpin the anticancer effects of cleistanthin A (CA) in two CRC cell lines, HCT 116, and SW480. At 48 h, CA exhibited apoptotic cytotoxic effects in both CRC cell lines, concomitant with reduction of an anti-apoptotic protein, survivin. Mechanistically, CA treatment significantly reduced the expression levels of ß-catenin and active-ß-catenin in a dose-dependent manner in both CRC cell lines. Moreover, CA suppressed the Wnt/ß-catenin signaling pathway by decreasing ß-catenin-mediated transcriptional activity and expression of ß-catenin target genes, AXIN2, CCND1, and survivin. Furthermore, CA also inhibited transcriptional activity in cells overexpressing a constitutively active ß-catenin S33Y, indicating a GSK-3ß-independent mechanism underlying the observed CA effects on CRC cells. Although cytotoxic activity was not observed with CA treatment at 24 h, cell migration and invasion were significantly reduced. In addition, CA suppressed V-type ATPase activity and focal adhesion kinase (FAK) phosphorylation. Collectively, our study reveals that CA has time-dependent effects on CRC cell phenotypes. First, short-term CA treatment inhibited CRC cell migration and invasion partly through the suppression of V-type ATPase activity. This suppression resulted in reduced FAK activation. Second, longer-term CA treatment decreased cell viability which correlated with the suppression of Wnt/ß-catenin signaling induced transcriptional activity. Altogether, our data suggest that CA has the potential to develop as an effective and novel therapeutic drug for CRC patients.

Crinamine Induces Apoptosis and Inhibits Proliferation, Migration, and Angiogenesis in Cervical Cancer SiHa Cells.

Crinumasiaticum 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.

Identification of reference genes for circulating long noncoding RNA analysis in serum of cervical cancer patients.

Circulating lncRNAs have attracted considerable attention as potential noninvasive biomarkers for diagnosing cancers. RT-qPCR is the canonical technique for detecting circulating RNA and depends largely on stable reference genes for data normalization. However, no systematic evaluation of reference genes for serum lncRNA has been reported for cervical cancer. Here, we profiled and validated lncRNA expression from serum of cervical cancer patients and controls using microarrays and RT-qPCR. We identified lncRNA RP11-204K16.1, XLOC_012542, and U6 small nuclear RNA as the most stable reference genes based on geNorm, NormFinder, BestKeeper, delta Ct, and RefFinder. These genes were suitable also for samples from different age groups or with hemolysis. Additionally, we discovered lncRNA AC017078.1 and XLOC_011152 as candidate biomarkers, whose expression was down-regulated in cervical cancer. Our findings could aid research on circulating lncRNA and the discovery of blood-based biomarkers for cervical cancer diagnosis.

Anticancer activity of arborinine from Glycosmis parva leaf extract in human cervical cancer cells.

Glycosmis parva is a small shrub found in Thailand. Ethyl acetate (EtOAc) extract from its leaves has been shown to exert anticancer effects in vitro; however, the compound responsible for this activity has not been isolated and characterized. In this study, we demonstrate that arborinine, a major acridone alkaloid in the EtOAc fraction, decreased proliferation and was strongly cytotoxic to HeLa cervical cancer cells without significantly affecting normal cells. The compound also inhibited tumor spheroid growth much more potently than chemotherapeutic drugs bleomycin, gemcitabine, and cisplatin. In addition, unlike cisplatin, arborinine activated caspase-dependent apoptosis without inducing DNA damage response. We further show that arborinine strongly suppressed cancer cell migration by downregulating expression of key regulators of epithelial-mesenchymal transition. Taken together, our data provide important insights into the molecular mechanism of arborinine's anticancer activity, supporting its potential use for treating cervical cancer.