Exploring the apoptotic effects of sericin on HCT116 cells through comprehensive nanostring transcriptomics and proteomics analysis.

Sericin, a silk protein from Bombyx mori (silkworms), has many applications, including cosmetics, anti-inflammation, and anti-cancer. Sericin complexes with nanoparticles have shown promise for breast cancer cell lines. Apoptosis, a programmed cell death mechanism, stops cancer cell growth. This study found that Sericin urea extract significantly affected HCT116 cell viability (IC50 = 42.00 ± 0.002 µg/mL) and caused apoptosis in over 80% of treated cells. S-FTIR analysis showed significant changes in Sericin-treated cells' macromolecule composition, particularly in the lipid and nucleic acid areas, indicating major cellular modifications. A transcriptomics study found upregulation of the apoptotic signaling genes FASLG, TNFSF10, CASP3, CASP7, CASP8, and CASP10. Early apoptotic proteins also showed that BAD, AKT, CASP9, p53, and CASP8 were significantly upregulated. A proteomics study illuminated Sericin-treated cells' altered protein patterns. Our results show that Sericin activated the extrinsic apoptosis pathway via the caspase cascade (CASP8/10 and CASP3/7) and the death receptor pathway, involving TNFSF10 or FASLG, in HCT116 cells. Upregulation of p53 increases CASP8, which activates CASP3 and causes HCT116 cell death. This multi-omics study illuminates the molecular mechanisms of Sericin-induced apoptosis, sheds light on its potential cancer treatment applications, and helps us understand the complex relationship between silk-derived proteins and cellular processes.

Exploring the Apoptotic-Induced Biochemical Mechanism of Traditional Thai Herb (Kerra™) Extract in HCT116 Cells Using a Label-Free Proteomics Approach.

Background and Objectives: Natural products have proven to be a valuable source for the discovery of new candidate drugs for cancer treatment. This study aims to investigate the potential therapeutic effects of "Kerra™", a natural extract derived from a mixture of nine medicinal plants mentioned in the ancient Thai scripture named the Takxila Scripture, on HCT116 cells. Materials and Methods: In this study, the effect of the Kerra™ extract on cancer cells was assessed through cell viability assays. Apoptotic activity was evaluated by examining the apoptosis characteristic features. A proteomics analysis was conducted to identify proteins and pathways associated with the extract's mechanism of action. The expression levels of apoptotic protein markers were measured to validate the extract's efficacy. Results: The Kerra™ extract demonstrated a dose-dependent inhibitory effect on the cells, with higher concentrations leading to decreased cell viability. Treatment with the extract for 72 h induced characteristic features of early and late apoptosis, as well as cell death. An LC-MS/MS analysis identified a total of 3406 proteins. The pathway analysis revealed that the Kerra™ extract stimulated apoptosis and cell death in colorectal cancer cell lines and suppressed cell proliferation in adenocarcinoma cell lines through the EIF2 signaling pathway. Upstream regulatory proteins, including cyclin-dependent kinase inhibitor 1A (CDKN1A) and MYC proto-oncogene, bHLH transcription factor (MYC), were identified. The expressions of caspase-8 and caspase-9 were significantly elevated by the Kerra™ extract compared to the chemotherapy drug Doxorubicin (Dox). Conclusions: These findings provide strong evidence for the ability of the Kerra™ extract to induce apoptosis in HCT116 colon cancer cells. The extract's efficacy was demonstrated by its dose-dependent inhibitory effect, induction of apoptotic activity, and modulation of key proteins involved in cell death and proliferation pathways. This study highlights the potential of Kerra™ as a promising therapeutic agent in cancer treatment.

Synchrotron Fourier Transform Infrared Microscopy Spectra in Cellular Effects of Janus Kinase Inhibitors on Myelofibrosis Cancer Cells.

Janus kinase (JAK) deregulation of the JAK/signal transducers and activators of transcription pathway leads to myelofibrosis that can be treated by JAK inhibitors including Ruxolitinib and Tofacitinib. Even though both inhibitors are effective against myelofibrosis, each of them has a different mode of action in the cells. Ruxolitinib is an inhibitor for selective JAK1/2, and Tofacitinib is an inhibitor for JAK3. This study evaluated the chemical fingerprints of TF-1 cells after JAK inhibitor treatments by the synchrotron Fourier transform infrared microspectroscopy (S-FTIR) spectrum. Tofacitinib and Ruxolitinib treatments in TF-1 cells were applied with a chemical fingerprint approach in S-FTIR spectroscopy and in vitro cytotoxicity in a cell-based assay. Principal component analysis or PCA was utilized to classify three cell treatments with three biochemical alteration absorbances of lipid vibration by the C-H stretching, protein amide I that appeared from the C=O stretching, and a P=O phosphodiester bond from nucleic acids. The results showed that the inhibition effect of Ruxolitinib on the TF-1 cell lines was two-fold higher than Tofacitinib. PCA distinguishes untreated and drug-treated cells by detecting cellular biochemical alteration. The loading plots identify that proteins and nucleic acids were the different main components in disparate cell treatments. Tofacitinib was distinct from the others in lipid and nucleic acid. The second derivative spectra of the three molecular components had decreased lipid production and accumulation, changes in secondary structures in proteins, and a high level of RNA overexpression in cell treatment. The JAK inhibitors caused different spectroscopic biomarkers of the modifications of secondary protein conformation, stimulated cell lipid accumulation, and phosphorylation from untreated cells. The alteration of cellular biochemical components suggests that FTIR is a potential tool to analyze specific patterns of drug cellular responses at the molecular level.