Pterostilbene Suppresses Ovarian Cancer Growth via Induction of Apoptosis and Blockade of Cell Cycle Progression Involving Inhibition of the STAT3 Pathway

Abstract

A growing body of evidence has demonstrated the promising anti-tumor effects of resveratrol in ovarian cancer cells, including its inhibitory effects on STAT3 activation. Nonetheless, the low bioavailability of resveratrol has reduced its attractiveness as a potential anti-cancer treatment. In contrast, pterostilbene, a stilbenoid and resveratrol analog, has demonstrated superior bioavailability, while possessing significant antitumor activity in multiple solid tumors. In this study, the therapeutic potential of pterostilbene was evaluated in ovarian cancer cells. Pterostilbene reduces cell viability in several different ovarian cancer cell lines by suppressing cell cycle progression and inducing apoptosis. Further molecular study has shown that pterostilbene effectively suppressed phosphorylation of STAT3, as well as STAT3 downstream genes that regulate cell cycle and apoptosis, indicating that inhibition of STAT3 pathway may be involved in its anti-tumor activity. The addition of pterostilbene to the commonly used chemotherapy cisplatin demonstrated synergistic antiproliferative activity in several ovarian cancer cell lines. Pterostilbene additionally inhibited cell migration in multiple ovarian cancer cell lines. The above results suggest that pterostilbene facilitates significant anti-tumor activity in ovarian cancer via anti-proliferative and pro-apoptotic mechanisms, possibly via downregulation of JAK/STAT3 pathway. Pterostilbene thus presents as an attractive non-toxic alternative for potential adjuvant or maintenance chemotherapy in ovarian cancer.

Pterostilbene Inhibits Human Renal Cell Carcinoma Cells Growth and Induces DNA Damage

“…Releasing cytochrome c subsequently interacted with pro-Caspase-9 to activate Caspase-9 and triggered the activation of Caspase-3, contributing to apoptosis. 24) Our results showed that PTE increased the expression levels of Bax, Bak, and Bad, decreased the expression level of Bcl2, activated Caspase-9, Caspase-3 and PARP in RCC cells. Overall, these results demonstrated that induction of the Caspase-dependent mitochondria-derived apoptosis resulted in the anticancer effects of PTE in RCC cells.…”

Activation of STAT3 and STAT5 Signaling in Epithelial Ovarian Cancer Progression: Mechanism and Therapeutic Opportunity

“…Another study has shown that siRNA mediated STAT3 downregulation suppressed SKOV3 cell growth and arrested the cell cycle in the G1 phase [70]. Several studies have highlighted that plant-derived phytochemicals, such as Pterostilbene, Cryptotanshinone and Curcumin, suppressed STAT3 activation, thereby reduced cancer cell proliferation and have been proposed as possible adjuvants of conventional chemotherapy [71][72][73].…”

Inhibitory Effects of Pinostilbene Hydrate on Melanogenesis in B16F10 Melanoma Cells via ERK and p38 Signaling Pathways

“…However, resveratrol is unstable in the environment. As a result, many derivatives of resveratrol have been studied, including PH [ 32 , 33 , 34 ]. In this study, we focused on the anti-melanogenic effects of PH and performed a mechanistic study to elucidate the signaling pathways in B16F10 cells.…”

“…However, resveratrol is unstable in the environment; it is very sensitive to UVR, air, and strong pH and is easily deformed. Thus, many resveratrol derivatives have been studied, and studies have found that methylated resveratrol derivatives have a good bioavailability and bioactivity [ 32 , 33 , 34 ]. One of the methylated resveratrol derivatives, pinostilbene hydrate (3,4′-dihydroxy-5-methoxystilbene), has been demonstrated to exert strong neuroprotective activity, as well as have anti-cancer effects on human colon cancer cells and anti-metastatic effects on human oral squamous cell carcinoma (OSCC) cells [ 34 , 35 , 36 , 37 ].…”