Abstract
The focus of this study is the anti-cancer effects of Cudrania tricuspidata stem (CTS) extract on cervical cancer cells. The effect of CTS on cell viability was investigated in HPV-positive cervical cancer cells and HaCaT human normal keratinocytes. CTS showed significant dose-dependent cytotoxic effects in cervical cancer cells. However, there was no cytotoxic effect of CTS on HaCaT keratinocytes at concentrations of 0.125–0.5 mg/mL. Based on this cytotoxic effect, we demonstrated that CTS induced apoptosis by down-regulating the E6 and E7 viral oncogenes. Apoptosis was detected by DAPI staining, annexin V-FITC/PI staining, cell cycle analysis, western blotting, RT-PCR, and JC-1 staining in SiHa cervical cancer cells. The mRNA expression levels of extrinsic pathway molecules such as Fas, death receptor 5 (DR5), and TNF-related apoptosis-inducing ligand (TRAIL) were increased by CTS. Furthermore, CTS treatment activated caspase-3/caspase-8 and cleavage of poly (ADP-ribose) polymerase (PARP). However, the mitochondrial membrane potential and expression levels of intrinsic pathway molecules such as Bcl-2, Bcl-xL, Bax, and cytochrome C were not modulated by CTS. Taken together, these results indicate that CTS induced apoptosis by activating the extrinsic pathway, but not the intrinsic pathway, in SiHa cervical cancer cells. These results suggest that CTS can be used as a modulating agent in cervical cancer.
Highlights
Cervical cancer is one of the most common diseases affecting women worldwide and remains a high cause of mortality among women in developing countries [1,2]
The cytotoxic efficacy of Cudrania tricuspidata stem (CTS) in human papilloma virus (HPV)-16-positive SiHa cells was slightly better than its efficacy in CaSki cells (Fig 2)
This effect might be due to the fact that the number of HPV genome copies in CaSki cells is higher than that of SiHa cells [24]
Summary
Cervical cancer is one of the most common diseases affecting women worldwide and remains a high cause of mortality among women in developing countries [1,2]. Epidemiological and clinical data suggest that infection with high-risk human papilloma virus (HPV) types, such as types 16 and 18, plays a major role in the multi-factorial etiology of cervical cancer [3]. Highrisk HPV oncoproteins E6 and E7 play important roles in maintaining cervical cancer cell. Effects of CTS Extract in Cervical Cancer Cells
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