Abstract
Increasing studies have reported that cancer stem cells (CSCs) play critical roles in therapeutic resistance, recurrence, and metastasis of tumors, including cervical cancer. Pterostilbene, a dimethylated derivative of resveratrol, is a plant polyphenol compound with potential chemopreventive activity. However, the therapeutic effect of pterostilbene against cervical CSCs remains unclear. In this study, we compared the anticancer effects of resveratrol and pterostilbene using both HeLa cervical cancer adherent and stem-like cells. Pterostilbene more effectively inhibited the growth and clonogenic survival, as well as metastatic ability of HeLa adherent cells than those of resveratrol. Moreover, the superior inhibitory effects of pterostilbene compared to resveratrol were associated with the enhanced activation of multiple mechanisms, including cell cycle arrest at S and G2/M phases, induction of ROS-mediated caspase-dependent apoptosis, and inhibition of matrix metalloproteinase (MMP)-2/-9 expression. Notably, pterostilbene exhibited a greater inhibitory effect on the tumorsphere-forming and migration abilities of HeLa cancer stem-like cells compared to resveratrol. This greater effect was achieved through more potent inhibition of the expression levels of stemness markers, such as CD133, Oct4, Sox2, and Nanog, as well as signal transducer and activator of transcription 3 signaling. These results suggest that pterostilbene might be a potential anticancer agent targeting both cancer cells and cancer stem-like cells of cervical cancer via the superior bioavailability to resveratrol.
Highlights
Cervical cancer is one of the most common types of female malignant tumor, with worldwide incidence of more than 500,000 cases and mortality rate of 9% per year [1]
These data demonstrate that pterostilbene is more potent in suppressing the growth and clonogenicity of cervical cancer adherent cells compared with resveratrol
Pterostilbene more strongly suppressed the expression of matrix metalloproteinase (MMP)-2 and MMP-9 compared with resveratrol (Figure 5B). These findings suggest that pterostilbene may possess enhanced activity in inhibiting the metastasis of cervical cancer cells than resveratrol, through more effective downregulation of MMP-2 and MMP-9 expression
Summary
Cervical cancer is one of the most common types of female malignant tumor, with worldwide incidence of more than 500,000 cases and mortality rate of 9% per year [1]. The worldwide death rate from cervical cancer has declined due to the current treatment modalities, including HPV vaccines, surgery, radiation therapy, and chemotherapy, the cancer recurrence, metastasis, and the adverse drug effects remain major problems [3]. Safer and more effective therapeutic options are needed to improve the treatment of cervical cancer. Accumulating evidence has demonstrated that cancer stem cells (CSCs), a small subpopulation of tumor cells with self-renewal and multi-lineage differentiation capacities, crucially drive the development, metastasis, relapse, and chemo/radio-resistance of cervical cancer [4,5].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
