Inhibitory Potential of Resveratrol in Cancer Metastasis: From Biology to Therapy

Abstract

Cancer metastasis is a significant challenge in cancer treatment, and most existing drugs are designed to inhibit tumor growth but are often ineffective in treating metastatic cancer, which is the leading cause of cancer-related deaths. Resveratrol, a polyphenol found in grapes, berries, and peanuts, has shown potential in preclinical studies as an anticancer agent to suppress metastasis. However, despite positive results in preclinical studies, little progress has been made in clinical trials. To develop resveratrol as an effective anticancer agent, it is crucial to understand its cellular processes and signaling pathways in tumor metastasis. This review article evaluates the current state and future development strategies of resveratrol to enhance its potency against cancer metastasis within its therapeutic dose. In addition, we critically evaluate the animal models used in preclinical studies for cancer metastasis and discuss novel techniques to accelerate the translation of resveratrol from bench to bedside. The appropriate selection of animal models is vital in determining whether resveratrol can be further developed as an antimetastatic drug in cancer therapy.

Enhancing the Bioavailability of Resveratrol: Combine It, Derivatize It, or Encapsulate It?

“…Furthermore, the anti-cancer properties of RSV against colorectal cancer have been proven through many clinical trials. In one explanation, RSV acts as a chemosensitizer that modifies many subcellular pathways (p38-MAPK, Akt/STAT3, IL-6/JAK, and other signaling pathways) altering angiogenesis, apoptosis, metastasis, and transcription factors (RSV inhibits the NF-kB and its promoted end-proteins) suppressing cancer plasticity [ 59 , 60 ]. In lung cancer as well, signaling pathways involved in cancer progression such as the mTOR, PI3K/Akt, Wnt/B-catenin are targeted by RSV as a mechanism to reduce the cancer burden [ 61 ].…”

Anti-Cancer Properties of Resveratrol: A Focus on Its Impact on Mitochondrial Functions

“…The ability of resveratrol to specifically alter numerous important cellular pathways implicated in tumor progression is one of the reasons it has gained so much attention as an anti-cancer agent with multiple applications [67][68][69][70][71]. A vast number of studies revealed the chemopreventive effect of resveratrol in various experimentally induced tumor models, such as skin, lung, gastric, colon, liver, pancreas, prostate, bladder, breast, ovarian, esophagus, thyroid, etc.…”

“…A vast number of studies revealed the chemopreventive effect of resveratrol in various experimentally induced tumor models, such as skin, lung, gastric, colon, liver, pancreas, prostate, bladder, breast, ovarian, esophagus, thyroid, etc. [67][68][69][70][71]. Resveratrol exposure induced differentiation in canine oral mucosal melanoma cells, enhancing their sensitivity to cisplatin and increasing the mRNA expression of melanoma differentiation markers, such as microphthalmia-associated transcription factor (MITF) [72].…”

“…Resveratrol can influence a wide range of processes in tumor cells, including cell growth, apoptosis, stimulate transcription, hormone signaling, and inhibit tumor cell proliferation, inflammation, redox signaling, and angiogenesis [67][68][69][70][71] (Figure 2). Resveratrol activates programmed cell death pathways in tumor cells.…”

“…It also suppresses promotion by inhibiting cyclooxygenase-2 activity [95], thus reducing prostaglandin synthesis and preventing DNA against oxidative damage. Moreover, resveratrol suppresses tumor progression due to induction of cancer cell cycle arrest, activation of apoptosis, and inhibition of angiogenesis and metastasis [71]. Due to its multifaceted effects on various phases of carcinogenesis, resveratrol is emerging as a potential anti-cancer agent.…”