naphthoquinones and Papillomavirus-Infections

We previously showed that microwave assisted synthesis is the best method for the synthesis of naphthoquinone amino acid and chloride-naphthoquinone amino acid derivatives by a complete evaluation of reaction conditions such as stoichiometry, bases, and pH influence. Following the same strategy, we synthesized chloride and non-chloride tyrosine, valine, and tryptophan-naphthoquinones achieving 85-95%, 80-92%, and 91-95% yields, respectively. The cyclic voltammetry profiles showed that both series of naphthoquinone amino acid derivatives mainly display one redox reaction process. Overall, chloride naphthoquinone amino acid derivatives exhibited redox potential values (E

Topics: Antineoplastic Agents; Carcinogenesis; Cell Line, Tumor; Cell Proliferation; Chlorides; Drug Design; Drug Screening Assays, Antitumor; Female; HaCaT Cells; Humans; Inhibitory Concentration 50; Microwaves; Naphthoquinones; Oxidation-Reduction; Papillomavirus Infections; Tryptophan; Tyrosine; Uterine Cervical Neoplasms; Valine

Human papillomaviruses (HPVs), for instance, HPV 16 and HPV 18, are concerned associated with cervical cancer. Thus, it is essential to suppress HPVs-in HPV-positive cervical cancer for treating cervical cancer. The purpose of this study was to explore the proposed molecular mechanisms, which that underlies the antintumor potential of juglone to treat of HPV-positive on cervical cancer cells. The results showed that juglone suppressed HPV-positive cell growth in a dose- and time-dependent way. In addition, cell invasion and metastasis were also inhibited by juglone. Nevertheless, when pin 1 was knocked down in HPV-positive cells, cell proliferation, invasion and metastasis were reduced. This study was designed to acquire an understanding of the mechanism of invasion and metastasis in HPV-positive cells suppressed by juglone. It provides evidence of the advantageous use of juglone in the future.

Topics: Cell Line, Tumor; Cell Proliferation; Female; HeLa Cells; Humans; Naphthoquinones; Neoplasm Invasiveness; Neoplasm Metastasis; Papillomaviridae; Papillomavirus Infections; Uterine Cervical Neoplasms

Cisplatin is one of the commonly used chemotherapeutic drugs for the treatment of head and neck squamous cell carcinoma (HNSCC). However, acquisition of cisplatin resistance is common in patients with HNSCC, and it often leads to local and distant failure. In this study, we showed that survivin expression is significantly upregulated in HNSCC primary tumors and cell lines. In addition, survivin levels were significantly higher in human papilloma virus-negative patients that normally respond poorly to cisplatin treatment. Survivin expression was further increased in cisplatin-resistant cells (CAL27-CisR) as compared with its parent cells (CAL27). Therefore, we hypothesized that targeting of survivin in HNSCC could reverse the resistant phenotype in tumor cells, thereby enhancing the therapeutic efficacy of cisplatin. We used both in vitro and in vivo models to test the efficacy of YM155, a small molecule survivin inhibitor, either as a single agent or in combination with cisplatin. YM155 significantly decreased survivin levels and cell proliferation in a dose-dependent manner. In addition, YM155 pretreatment significantly reversed cisplatin resistance in cancer cells. Interestingly, YM155 treatment altered the dynamic localization of survivin in cells by inducing a rapid reduction in cytoplasmic survivin, which plays a critical role in its antiapoptotic function. In a severe combined immunodeficient mouse xenograft model, YM155 significantly enhanced the antitumor and antiangiogenic effects of cisplatin, with no added systemic toxicity. Taken together, our results suggest a potentially novel strategy to use YM155 to overcome the resistance in tumor cells, thereby enhancing the effectiveness of the chemotherapy in HNSCC.

Topics: Adult; Aged; Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Cisplatin; Cytoplasm; Drug Synergism; Female; Head and Neck Neoplasms; Human papillomavirus 16; Humans; Imidazoles; Inhibitor of Apoptosis Proteins; Inhibitory Concentration 50; Male; Mice; Mice, SCID; Middle Aged; Naphthoquinones; Neovascularization, Pathologic; Papillomavirus Infections; Statistics, Nonparametric; Survivin; Tissue Array Analysis; Tumor Burden; Up-Regulation; Xenograft Model Antitumor Assays