MiRNA-873-5p Acts as a Potential Novel Biomarker and Promotes Cervical Cancer Progression by Regulating ZEB1 via Notch Signaling Pathway

Objective: Our group aimed to investigate the expression pattern of miRNA-873-5p in cervical cancer (CC) patients and its association with CC progression. Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was applied for the examination of the expressions of miRNA-873-5p in both CC specimens and cell lines. The clinical significance of miRNA-873-5p was statistically analyzed. MTT, colony formation, Transwell and flow cytometry assays were used to detect cell proliferation, metastasis, and apoptosis changes of Hela and Siha cell line. Luciferase reporter assays and Western blots were utilized to identify the target genes of miRNA-873-5p. Western blot and RT-PCR were used to judge the dysregulation of Notch signaling. Results: Our results indicated that miRNA-873-5p expression was distinctly reduced in CC patients. Low miRNA-873-5p expressions were distinctly correlated with positively distant metastasis, The International Federation of Gynecology and Obstetrics (FIGO) stage and poor prognosis of CC patients. A functional assay using miRNA-873-5p mimics indicated that overexpression of miRNA-873-5p distinctly suppressed CC cells proliferation and metastasis, and promoted apoptosis. Bioinformatic assays revealed that miRNA-873-5p may target the 3’-UTR of ZEB1 and lead to the suppression of its translation, which was verified by the use of luciferase assays. Finally, overexpression of miRNA-873-5p suppressed the expressions of Jag1, Maml2 and Hey1. Conclusion: Taken together, we firstly provided evidence that miRNA-873-5p expression was a poor favorable factor for CC patients, and the use of miRNA-873-5p may represent a and potential biomarker and promising therapeutic approach for CC.

Chloroform fraction of Chaetomorpha brachygona, a marine green alga from Indian Sundarbans inducing autophagy in cervical cancer cells in vitro

Sundarbans Mangrove Ecosystem (SME) is a rich repository of bioactive natural compounds, with immense nutraceutical and therapeutic potential. Till date, the algal population of SME was not explored fully for their anticancer activities. Our aim is to explore the potential of these algal phytochemicals against the proliferation of cervical cancer cells (in vitro) and identify the mode of cell death induced in them. In the present work, the chloroform fraction of marine green alga, Chaetomorpha brachygona was used on SiHa cell line. The algal phytochemicals were identified by GCMS, LCMS and column chromatography and some of the identified compounds, known for significant anticancer activities, have shown strong Bcl-2 binding capacity, as analyzed through molecular docking study. The extract showed cytostatic and cytotoxic activity on SiHa cells. Absence of fragmented DNA, and presence of increased number of acidic vacuoles in the treated cells indicate nonapoptotic cell death. The mode of cell death was likely to be autophagic, as indicated by the enhanced expression of Beclin 1 and LC3BII (considered as autophagic markers) observed by Western blotting. The study indicates that, C. brachygona can successfully inhibit the proliferation of cervical cancer cells in vitro.

Anti-proliferative effect of Oyster mushroom, Pleurotus from Florida (misnomer) P. florida (Agaricomycetes) against HeLa and SIHA cervical cancer cells: Mushroom-boon for cancer therapies

Introduction and Aim: Worldwide, people are suffering from the increased risk of cancer due to change in lifestyle, feeding habit and quality of food. To overcome this global problem, Mushroom act as a magic wand. The recent investigations reveal that cancer prevalence is inversely proportional to the intake of mushroom; this is because of its proteins, vitamins, carbohydrate and antioxidants contents. Materials and Methods: Among various species of mushrooms, Pleurotus mushrooms are considered as nutraceuticals i.e. it has nutritional and medicinal values. However, mushroom products and extracts possess immunomodulating and direct cytotoxic effect on cancer cells. Results: The results from the present study shows the potential cytotoxic effect of Pleurotus from Florida against cervical cancer (SIHA) cell line through apoptosis. When SIHA cells were incubated with varying concentration of methanolic extract of Pleurotus from Florida for time (48 hrs). The MTT assay revealed the cytotoxic activity of MME of Pleurotus from Florida in a dose dependent manner. The cell cycle analysis of the SIHA cells revealed that MME of Pleurotus from Florida have anti-cancerous activity. Conclusion: The study could be concluded as the Pleurotus from Florida extract can be useful in the treatment of cervical cancers. The chemical compounds present in the P. from Florida might be useful in the development of drug for the treatment of cancer patients.

Discovery of 12O—A Novel Oral Multi-Kinase Inhibitor for the Treatment of Solid Tumor

A novel series of pyrimidine-benzotriazole derivatives have been synthesized and evaluated for their anticancer activity against human solid tumor cell lines. The most promising molecule 12O was identified for its excellent antiproliferative activities, especially against the SiHa cell line with IC50 value as 0.009 μM. Kinase inhibition assay assessed 12O was a potential multi-kinase inhibitor, which possessed potent inhibitory activities against cyclin-dependent kinases (CDKs) and fms-like tyrosine kinase (FLT) with IC50 values in the nanomolar range. Molecular docking studies illustrated that the introduction of triazole moiety in 12O was critical for CDKs inhibition. In addition, 12O inhibited cancer cell proliferation, colony-formation, and cell cycle progression and provoked apoptotic death in vitro. In an SiHa xenograft mouse model, a once-daily dose of compound 12O at 20 mg/kg significantly suppressed the tumor growth without obvious toxicity. Taken together, 12O provided valuable guide for further structural optimization for CDKs and FLT inhibitors.

Physicochemical Characterization of Curcumin Loaded Chitosan Nanoparticles: Implications in Cervical Cancer

Background: Curcumin is a potent anticancer agent and has great potential efficacy against different types of cancers. A major disadvantage of curcumin, however, is its poor solubility and bioavailability. Objective: The aim of the present work is to synthesize chitosan and curcumin-loaded chitosan nanoparticles and their characterization through various physicochemical methods and cellular uptake in cervical cancer cell line SiHa. Method: Chitosan nanoparticles were synthesized through the method of ionic gelation of chitosan with sodium Tripolyphosphate (TPP). In addition, the internal structure of chitosan nanoparticles and curcumin loaded chitosan nanoparticles were characterized by DLS, UV-Visible spectrophotometer, DSC, LCMS and LDH assay. Results: The studies presented demonstrate that curcumin-loaded chitosan nanoparticles showed increased uptake in the SiHa cells as compared to free curcumin and chitosan nanoparticles did not show any significant uptake in SiHa cell line. The curcumin-loaded chitosan nanoparticles released more lactate and lower ATP as compared to native curcumin in cervical cancer lines such as SiHa, CaSki and HeLa. Conclusion: Thus, chitosan based curcumin nanoparticles could be used as a potent vector / delivery agent for drug targeting in the treatment of cervical cancer.