Background: Infection with a high-risk human papillomavirus (HR-HPV), especially, HPV16 is the most important risk factor for cervical cancer. Oncoproteins (E6 and E7) of HR-HPV play an important role in cervical cancer development involved by several mechanisms including degradation of tumor suppressor protein p53 and anti-apoptosis. Andrographolide is a diterpenoid lactone isolated from a traditional herbal medicine,Andrographis paniculata. It has been reported to induce apoptosis in different cancer cell lines. However, the effects on regulation of HPV16 transcription, oncogene expression and induction of cervical cancer cells apoptosis are still unclear. This study investigated the effects of andrographolide on HPV16 transcription activity, E6 oncogene expression and p53 protein level as a downstream process involved in cell apoptosis. Methods: Sub-cytotoxicity of the andrographolide compound was determined by MTT assay. C33A cell line, an HPV-negative cervical cancer cell line, was transfected by reporting vector containing long control region of HPV16 European and Asian variant and treated with compound for analysis of promoter transcription. SiHa cell line, an HPV16-positive cervical cancer cell line, was treated with the compound for 24 and 48 hr. The oncogene E6 and p53 expression were analyzed by SYBR Green real-time PCR and western blot. Cell apoptosis was analyzed by flow cytometry. Results: Andrographolide exhibited cytotoxic effects with IC50 values of 152.34 M and 142.23 M, whereas sub-cytotoxic values of 9.71 M and 13.88 M in C33A and SiHa cells, respectively. The result demonstrated that sub-cytotoxic concentration of andrographolide suppressed LCR transcription activity of both HPV16 European and Asian variant in transfected-C33A cells. Andrographolide also significantly inhibited E6 oncogene expression in SiHa cells at 24 h post treatment. Importantly, inhibitory effect was increased by increasing concentration, but not time increasing. After 48 h post treatment, the p53 was restored expression in SiHa cells. In addition, andrographolide also significantly induced apoptosis of SiHa cells in concentration-dependent manner. Conclusion: This result demonstrated that the andrographolide induced SiHa cells apoptosis via suppression of HPV16 transcription activity, leading to decreased E6 oncoprotein and restored p53. These findings imply that the andrographolide may be an effective agent for cervical cancer prevention and treatment.
An outbreak of a respiratory disease with severe acute respiratory syndrome (SARS)like manifestations emerged in late December 2019 in the Wuhan city of China. The causative agent of this disease was later identified to be a novel Coronavirus. Subsequently, the disease was named coronavirus disease 2019 (COVID-19) by the World Health Organisation and later declared as a pandemic. The outbreak of COVID-19 came with many misinformation and misconceptions about viruses and the COVID-19 disease. Questions have been asked by non -virologists and the general public about what viruses are. Some wondered if viruses are living organisms or not. While some asked how big viruses are or if all viruses and the COVID-19 virus is artificially created. Yet others attributed the outbreak to the new quantum leap in the electromagnet field; the latest 5G technology. There are also concerns raised about the new virus being a bioweapon or an act of biowarfare. These numerous questions needed to be clarified concisely with available scientific knowledge. Thus, this review is providing answers to the 10 frequently asked questions aimed at informing the non -virologist in the academic field and beyond.
Conclusion: HPAI H5 viruses bearing the N6 subtype neuraminidase and mammalian adaptation markers in the polymerase genes are capable of causing lethal infection in ferrets as well as transmitting to uninfected animals in a direct contact setting. The heterogeneity in mammalian virulence among H5N6 viruses underscores the necessity of in vivo evaluation of H5Nx viruses as they continue to evolve and pose a threat to human health.
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