Myeloid cell leukemia 1 (Mcl-1) and B-cell lymphoma 2 (Bcl-2) proteins are promising targets for cancer therapy. Here, we investigated the structure–activity relationships (SARs) and performed molecular docking analysis of renieramycin T (RT) and its analogues and identified the critical functional groups of Mcl-1 targeting. RT have a potent anti-cancer activity against several lung cancer cells and drug-resistant primary cancer cells. RT mediated apoptosis through Mcl-1 suppression and it also reduced the level of Bcl-2 in primary cells. For SAR study, five analogues of RT were synthesized and tested for their anti-cancer and Mcl-1- and Bcl-2-targeting effects. Only two of them (TM-(–)-18 and TM-(–)-4a) exerted anti-cancer activities with the loss of Mcl-1 and partly reduced Bcl-2, while the other analogues had no such effects. Specific cyanide and benzene ring parts of RT’s structure were identified to be critical for its Mcl-1-targeting activity. Computational molecular docking indicated that RT, TM-(–)-18, and TM-(–)-4a bound to Mcl-1 with high affinity, whereas TM-(–)-45, a compound with a benzene ring but no cyanide for comparison, showed the lowest binding affinity. As Mcl-1 helps cancer cells evading apoptosis, these data encourage further development of RT compounds as well as the design of novel drugs for treating Mcl-1-driven cancers.

Background/Aim: Epithelial to mesenchymal transition (EMT) is a cellular process that facilitates cancer metastasis. Therefore, therapeutic approaches that target EMT have garnered increasing attention. The present study aimed to examine the in vitro effects of ephemeranthol A on cell death, migration, and EMT of lung cancer cells. Materials and Methods: Ephemeranthol A was isolated from Dendrobium infundibulum. Non-small cell lung cancer cells H460 were treated with ephemeranthol A and apoptosis was evaluated by Hoechst 33342 staining. Anoikis resistance was determined by soft agar assay. Wound healing assay was performed to test the migration. The regulatory proteins of apoptosis and cell motility were determined by western blot. Results: Treatment with ephemeranthol A resulted in a concentration-dependent cell apoptosis. At non-toxic concentrations, the compound could inhibit anchorage-independent growth of the cancer cells, as indicated by the decreased colony size and number. Ephemeranthol A also exhibited an inhibitory effect on migration. We further found that ephemeranthol A exerts its antimetastatic effects via inhibition of EMT, as indicated by the markedly decrease of N-cadherin, vimentin, and Slug. Furthermore, the compound suppressed the activation of focal adhesion kinase (FAK) and protein kinase B (Akt) proteins, which are key regulators of cell migration. As for the anticancer activity, ephemeranthol A induced apoptosis by decreasing Bcl-2 followed by the activation of caspase 3 and caspase 9. Conclusion: The pro-apoptotic and anti-migratory effects of ephemeranthol A on human lung cancer cells support its use for the development of novel anticancer therapies.

Hyperglycemia and inflammation are hallmarks of the prediabetes stage, which has the potential to develop into diabetes mellitus. In this stage, lifestyle changes and exercise are recommended and have been shown to be effective. However, there has been insufficient study investigating the impact of Ruesi Dadton (RD) exercise on prediabetes. Therefore, this study aimed to investigate the effect of RD exercise on biomarkers of glycemic level including fasting plasma glucose (FPG), the 2 h oral glucose tolerance test (OGTT), hemoglobin A1C (HbA1C), the biomarkers of inflammation C-reactive protein (CRP) and interleukin 6 (IL-6), and body mass index (BMI) on prediabetes during 12-week RD exercise. A total of 64 participants were randomly assigned into two groups, RD and control (CON), and were tested by measuring their glycemic levels to screen for prediabetes. The RD group was instructed to perform 10 postures of RD exercise in 60 min, three times a week. The CON group received standard lifestyle recommendations that were not pharmacologically managed. The results reveal that the RD group experienced a significant decrease in FPG, OGTT, HbA1C, and IL-6 (p < 0.01), and BMI and CRP (p < 0.05) compared to the CON group. In addition, the CON group had considerably higher glycemic levels, BMI and IL-6 levels (p < 0.01). Our study demonstrates that RD could decrease the biomarkers of glycemic level and inflammation during 12 weeks of RD exercise in prediabetes. These findings suggest that RD exercise is an effective approach for reducing systemic inflammation and controlling glycemic levels in prediabetic patients.

Metal nanomaterials can enhance the efficacy of current cancer therapies. Here, we show that Ti_0.8O₂ nanosheets cause cytotoxicity in several lung cancer cells but not in normal cells. The nanosheet-treated cells showed certain apoptosis characteristics. Protein analysis further indicated the activation of the p53-dependent death mechanism. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analyses revealed the cellular uptake of the nanosheets and the induction of cell morphological change. The nanosheets also exhibited a substantial apoptosis effect on drug-resistant metastatic primary lung cancer cells, and it was found that the potency of the nanosheets was dramatically higher than standard drugs. Ti_0.8O₂ nanosheets induce apoptosis through a molecular mechanism involving peroxynitrite (ONOO⁻) generation. As peroxynitrite is known to be a potent inducer of S-nitrosylation, we further found that the nanosheets mediated the S-nitrosylation of p53 at C182, resulting in higher protein-protein complex stability, and this was likely to induce the surrounding residues, located in the interface region, to bind more strongly to each other. Molecular dynamics analysis revealed that S-nitrosylation stabilized the p53 dimer with a $\mathsf{\Delta }{G}_{\mathrm{bind}}^{\mathrm{residue}}$ of <−1.5 kcal/mol. These results provide novel insight on the apoptosis induction effect of the nanosheets via a molecular mechanism involving S-nitrosylation of the p53 protein, emphasizing the mechanism of action of nanomaterials for cancer therapy.

Lung cancer metastasis is a multifaceted process that accounts for 90% of cancer deaths. According to several studies, the epithelial–mesenchymal transition (EMT) plays an essential role in lung cancer metastasis. Therefore, this study aimed to investigate the potential pharmacological effect of cycloartocarpin on the suppression of metastasis-related behaviors and EMT. An MTT assay was used to examine cell viability. Cell migration was determined using a wound healing assay. Anchorage-independent cell growth was also performed. Western blot analysis was used to identify the key signaling proteins involved in the regulation of EMT and migration. The results found that non-toxic concentrations of cycloartocarpin (10–20 μM) effectively suppressed cell migration and attenuated anchorage-independent growth in H292, A549, and H460 cells. Interestingly, these effects were consistent with the findings of Western blot analysis, which revealed that the level of phosphorylated focal adhesion kinase (p-FAK), phosphorylated ATP-dependent tyrosine kinase (p-AKT), and cell division cycle 42 (Cdc42) were significantly reduced, resulting in the inhibition of the EMT process, as evidenced by decreased N-cadherin, vimentin, and slug expression. Taken together, the results suggest that cycloartocarpin inhibits EMT by suppressing the FAK/AKT signaling pathway, which is involved in Cdc42 attenuation. Our findings demonstrated that cycloartocarpin has antimetastatic potential for further research and development in lung cancer therapy.

In Thailand, wild yam, or Dioscorea hispida Dennst., is a starchy crop that is usually underutilized in industry. The purpose of this study was to isolate the starch and extract the phytochemical from D. hispida and use them in cosmetics. Starch was used instead of talcum, which can cause pulmonary talcosis in dusting powder formulas (DP 1-5). GC-MS was used to identify the bioactive components present in the ethanolic extract of D. hispida. The main compounds were identified as 9,12-octadecadienoic acid (Z,Z)- (6.51%), stigmasta-5,22-dien-3-ol, (3.beta.,22E)- (6.41%), linoleic acid ethyl ester (5.72%), (Z,Z)-9,12-octadeca-dienoic acid, 2,3-dihydroxy-propyl (3.89%), and campesterol (3.40%). Then, the extract was used as an ingredient in facial sleeping mask gel formulas (SM 1–SM 5). Stability tests, physical characteristics, enzyme inhibitions, and sensitization dermal toxicity tests were used to evaluate the DP and SM formulations. The results showed that the fresh tubers of D. hispida showed a 12.5% w/w starch content. The findings demonstrated that starch powder had a restricted size distribution, ranging from 2 to 4 μm, and a smooth surface that was polygonal. Following stability testing, the color, odor, size, and flowability of all DP formulations did not significantly differ. The SEM investigation revealed that DP particles were homogenous. For the sensitization dermal toxicity test, DP denoted no erythema or skin irritation in the guinea pigs. After stability testing, the colors of the SM formulas were deeper, and their viscosity slightly increased. The pH did not significantly change. After the stability test, SM formulas that contained Glycyrrhiza glabra and D. hispida extracts exhibited stable tyrosinase and elastase inhibitory activities, respectively. In the sensitization dermal toxicity test, guinea pigs showed skin irritation at level 2 (not severe) from SM, indicating that redness developed. All of these findings indicate that D. hispida is a plant that has potential for use in the cosmetics industry. Furthermore, D. hispida starch can be made into a beauty dusting powder, and more research should be conducted to develop an effective remedy for patients or those with skin problems.