Uncovering the Anticancer Potential of Polydatin: A Mechanistic Insight

Abstract

Polydatin or 3-O-β-d-resveratrol-glucopyranoside (PD), a stilbenoid component of Polygonum cuspicadum (Polygonaceae), has a variety of biological roles. In traditional Chinese medicine, P. cuspicadum extracts are used for the treatment of infections, inflammation, and cardiovascular disorders. Polydatin possesses a broad range of biological activities including antioxidant, anti-inflammatory, anticancer, and hepatoprotective, neuroprotective, and immunostimulatory effects. Currently, a major proportion of the population is victimized with cervical lung cancer, ovarian cancer and breast cancer. PD has been recognized as a potent anticancer agent. PD could effectively inhibit the migration and proliferation of ovarian cancer cells, as well as the expression of the PI3K protein. The malignancy of lung cancer cells was reduced after PD treatments via targeting caspase 3, arresting cancer cells at the S phase and inhibiting NLRP3 inflammasome by downregulation of the NF-κB pathway. This ceases cell cycle, inhibits VEGF, and counteracts ROS in breast cancer. It also prevents cervical cancer by regulating epithelial-to-mesenchymal transition (EMT), apoptosis, and the C-Myc gene. The objective of this review is thus to unveil the polydatin anticancer potential for the treatment of various tumors, as well as to examine the mechanisms of action of this compound.

Keywords: 3-O-β-d-resveratrol-glucopyranoside; breast cancer; cervical cancer; lung cancer; ovarian cancer; phenol compounds; polydatin.

Figure 1

Resveratrol and polydatin isomers, trans and cis.

Figure 2

Potential dietary sources of polydatin derivative (transisomer). The quantities of PD in each fruit and vegetable have been derived from Peng et al. [35].

Figure 3

Polydatin (PD) potential to inhibit the G1 phase of the cell cycle along with other oncogenic pathways. PD appears to interfere with Creb phosphorylation, which downregulates Cyclin D1 and thus terminates the cell cycle at G1 phase and in turn inhibits breast cancer growth. PIN1: peptidyl-prolyl cis/trans isomerase, CEP55: Centrosomal protein 55, CK2: casein kinase 2, Rb: the retinoblastoma protein.

Figure 4

Mechanistic illustration of polydatin activity in the treatment of breast cancer through p53 activation. Activation of p53 leads to activation of p21 and Bax, which in turn leads to cell cycle arrest and apoptosis. ↑ Upregulation, ↓ Downregulation.

Figure 5

The mechanistic approach of polydatin (PD) activity in terminating cell cycle in cervical cancer cells. PD causes the downregulation of the c-Myc gene, which alters two mechanisms involved in cervical cancer. PD causes upregulation of p21 and p27, and also induces repression of CDK4 and cyclin D1 as well as CDK2 and cyclin E1; their dysregulation ultimately terminates the G0/G1 phase of the cell cycle. In the second pathway, PD causes Snail and Slug expressions, leading to upregulation of E-cadherin expression and downregulation of N-cadherin, and thus impairing cell metastasis in cervical cancer.

Figure 6

Anticancer effects of polydatin on lung cancer via the apoptotic pathway by increasing BAX levels, decreasing Bcl-2 levels and increasing caspase-3 levels, induction of cell cycle arrest at S phase by decreasing the cyclin D1 levels, and inhibition of the NLRP3 inflammasome by suppressing the NF-kB pathway in tumor cells. Upregulation ↑ Downregulation ↓.

Figure 7

Schematic overview of polydatin activity on the PI3K/AKT/mTOR signaling pathway with different strategies for inhibition. PD induces apoptosis in cancer cells through the PI3K/Akt/mTOR signaling pathway and protects against inflammatory damage, as well as inhibiting cell proliferation, survival and protein synthesis through protein phosphorylation.

Figure 8

Polydatin anticancer mechanisms: upregulation or downregulation of various pathways.