Resveratrol and Pterostilbene Exhibit Anticancer Properties Involving the Downregulation of HPV Oncoprotein E6 in Cervical Cancer Cells

Abstract

Cervical cancer is one of the most common cancers in women living in developing countries. Due to a lack of affordable effective therapy, research into alternative anticancer compounds with low toxicity such as dietary polyphenols has continued. Our aim is to determine whether two structurally similar plant polyphenols, resveratrol and pterostilbene, exhibit anticancer and anti-HPV (Human papillomavirus) activity against cervical cancer cells. To determine anticancer activity, extensive in vitro analyses were performed. Anti-HPV activity, through measuring E6 protein levels, subsequent downstream p53 effects, and caspase-3 activation, were studied to understand a possible mechanism of action. Both polyphenols are effective agents in targeting cervical cancer cells, having low IC50 values in the µM range. They decrease clonogenic survival, reduce cell migration, arrest cells at the S-phase, and reduce the number of mitotic cells. These findings were significant, with pterostilbene often being more effective than resveratrol. Resveratrol and to a greater extent pterostilbene downregulates the HPV oncoprotein E6, induces caspase-3 activation, and upregulates p53 protein levels. Results point to a mechanism that may involve the downregulation of the HPV E6 oncoprotein, activation of apoptotic pathways, and re-establishment of functional p53 protein, with pterostilbene showing greater efficacy than resveratrol.

The Preventive Effects of Pterostilbene on the Exercise Intolerance and Circadian Misalignment of Mice Subjected to Sleep Restriction

“…PTE as a dimethylated analog of RSV, possesses promising health benefits, including anti‐oxidative, anti‐cancer, and anti‐inflammatory, similar to those of RSV. [ 24,44 ] The present study showed that PTE indeed had beneficial effects in SR mice. It maintained food intake, body weight and FPG to the normal levels in SR mice.…”

“…It has attracted considerable attention because of its promising health benefits similar to those of RSV and the higher oral bioavailability than RSV. [ 24,25 ] Also, it is nontoxic to human even at high dose. [ 26 ] However, to the best of our knowledge, there has been no study demonstrating the effects of PTE on circadian rhythm and endurance capacity.…”

Resveratrol Suppresses the Growth and Metastatic Potential of Cervical Cancer through Inhibiting STAT3Tyr705 Phosphorylation

“…Several studies have shown that resveratrol induces autophagy and apoptotic cell death in cervical cancer cells (9,10) and suppresses migration and invasion of human cervical cancer cells (11). Resveratrol significantly inhibits the occurrence and development of cervical cancer by regulating phospholipid scramblase 1 (12,13) and exhibits antitumor activity on HPV E6-positive cervical cancer (14,15). These studies suggest that resveratrol is a potential chemotherapeutic drug for cervical cancer.…”

Pterostilbene Suppresses both Cancer Cells and Cancer Stem-Like Cells in Cervical Cancer with Superior Bioavailability to Resveratrol

“…Pterostilbene effectively suppressed cancer progression and metastasis by regulating apoptosis-dependent and apoptosis-independent signaling pathways. Accumulating evidence has shown that the anticancer effects of pterostilbene against cervical cancer are associated with the induction of apoptosis by activating the endoplasmic reticulum (ER)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and downregulating the HPV oncoprotein E6 that causes the degradation of tumor suppressor protein p53 [17,33].…”

“…However, resveratrol has a low bioavailability that may lower its biological efficacy, while pterostilbene is more lipophilic, and thus, it exhibits better bioavailability [15]. Pterostilbene shows stronger antiproliferative and apoptotic effects than those shown by resveratrol in the human colon and cervical cancer cells [16,17]. However, the therapeutic effect and anticancer mechanism of pterostilbene against cervical CSCs compared to resveratrol have not been studied.…”