shikonin and Uterine-Cervical-Neoplasms

Shikonin, the main ingredient of. MTT, wound-healing, transwell assays and flow cytometry experiments were used to measure cell growth, migration, invasion, and cell cycle analysis. Western blot was used to examine protein levels of Snail, Vimentin and E-cadherin. The expression level of miR-183-5p was measured via qRT-PCR. The E-cadherin promoter activity was detected via Secrete-PairTM Dual Luminescence Assay Kit. The transient transfection experiments were used for silencing of E-cadherin and overexpression of Snail genes. Tumor xenograft and bioluminescent imaging experiments were carried out to confirm the in vitro findings.. We showed that shikonin inhibited cell viability, migration and invasion, and induced cell cycle arrest in a dose-dependent manner in cervical cancer Hela and C33a cells. Mechanistically, we found that shikonin increased miR-183-5p expression and inhibited expression of transcription factor Snail protein. The mimics of miR-183-5p reduced, while the inhibitors of miR-183-5p reversed shikonin-inhibited Snail protein expression. In addition, shikonin decreased Vimentin, increased E-cadherin protein expressions and E-cadherin promoter activity, the latter was reversed in cells transfected with exogenous Snail overexpression vectors. Moreover, silencing of E-cadherin significantly abolished shikonin-inhibited cervical cancer cell growth. Similar findings were also observed in vivo using one xenograft mouse model.. Our results show that shikonin inhibits EMT through inhibition of Snail and stimulation of miR-183-5p expressions, which resulted in induction of E-cadherin expression. Thus, blockade of EMT could be a novel mechanism underlying the anti-cervical cancer effects of shikonin.

Topics: Animals; Antigens, CD; Antineoplastic Agents, Phytogenic; Cadherins; Cell Line, Tumor; Dose-Response Relationship, Drug; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Lithospermum; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs; Naphthoquinones; Snail Family Transcription Factors; Uterine Cervical Neoplasms; Xenograft Model Antitumor Assays

In current study, a series of shikonin derivatives were synthesized and its anticancer activity was evaluated. As a result, PMMB232 showed the best antiproliferation activity with an IC

Topics: Antineoplastic Agents; Apoptosis; Carboxylic Acids; Coumarins; Drug Evaluation, Preclinical; Female; HeLa Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Molecular Docking Simulation; Naphthoquinones; Uterine Cervical Neoplasms