Resveratrol as sensitizer in colorectal cancer plasticity

Abstract

Despite tremendous medical treatment successes, colorectal cancer (CRC) remains a leading cause of cancer deaths worldwide. Chemotherapy as monotherapy can lead to significant side effects and chemoresistance that can be linked to several resistance-activating biological processes, including an increase in inflammation, cellular plasticity, multidrug resistance (MDR), inhibition of the sentinel gene p53, and apoptosis. As a consequence, tumor cells can escape the effectiveness of chemotherapeutic agents. This underscores the need for cross-target therapeutic approaches that are not only pharmacologically safe but also modulate multiple potent signaling pathways and sensitize cancer cells to overcome resistance to standard drugs. In recent years, scientists have been searching for natural compounds that can be used as chemosensitizers in addition to conventional medications for the synergistic treatment of CRC. Resveratrol, a natural polyphenolic phytoalexin found in various fruits and vegetables such as peanuts, berries, and red grapes, is one of the most effective natural chemopreventive agents. Abundant in vitro and in vivo studies have shown that resveratrol, in interaction with standard drugs, is an effective chemosensitizer for CRC cells to chemotherapeutic agents and thus prevents drug resistance by modulating multiple pathways, including transcription factors, epithelial-to-mesenchymal transition-plasticity, proliferation, metastasis, angiogenesis, cell cycle, and apoptosis. The ability of resveratrol to modify multiple subcellular pathways that may suppress cancer cell plasticity and reversal of chemoresistance are critical parameters for understanding its anti-cancer effects. In this review, we focus on the chemosensitizing properties of resveratrol in CRC and, thus, its potential importance as an additive to ongoing treatments. Graphical abstract

Prevention and Co-Management of Breast Cancer-Related Osteoporosis Using Resveratrol

“…Additionally, resveratrol has recently received attention as anti-adipogenic phytonutrient for the prevention and management of obesity and obesity-related metabolic syndrome [ 150 ], highlighting its potential role in the prevention of numerous chronic inflammatory diseases ( Figure 6 ). The natural polyphenol is also a promising adjuvant approach to chemosensitization in the setting of conventional cancer therapies to prevent therapy resistance and reduce systemic side effects [ 151 ]. The great potential of the phytopharmaceutical is illustrated in particular by its property to act both catabolically, as on BC [ 56 ], and anabolically, as on OP [ 149 ].…”

“…Numerous in vitro and in vivo studies have demonstrated the anti-proliferative, pro-apoptotic, anti-angiogenic, and chemosensitizing effects of resveratrol on various types of cancer, including BC [ 151 ], by attenuating pro-inflammatory mediators through the modulation of NF-κB and STAT3 signaling in BC cells ( Figure 7 ) [ 157 , 158 ].…”

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 ].…”

The role of polyphenols in the prevention and treatment of cancer

“…[56] Moreover, several studies using a mouse xenographic model demonstrated, in addition to the chemosensitizing effect, an additional radiosensitizing effect against colorectal cancer cells. [57,58]…”