Cancer remains a formidable challenge, with treatment efficacy often hampered by drug resistance and the presence of cancer stem cells (CSCs). In the pursuit of more effective therapeutic strategies, natural compounds that can synergize with existing treatments or target resistant cell populations are of immense interest. Pterostilbene (PTS), a potent polyphenol, is showing significant promise in augmenting cancer therapy.

Pterostilbene exhibits a broad spectrum of anticancer activities, acting through multiple mechanisms. It can inhibit cancer cell proliferation, induce apoptosis (programmed cell death), modulate key signaling pathways like PI3K/Akt and MAPK, and interfere with cancer cell migration and invasion. These inherent anticancer properties make it a valuable agent in its own right.

One of the critical areas where pterostilbene shows potential is in overcoming drug resistance. Many cancer cells develop resistance to chemotherapy agents through various mechanisms, such as increased drug efflux or enhanced DNA repair. Pterostilbene has been shown to reverse multidrug resistance in cancer cells, suggesting it can re-sensitize them to conventional chemotherapy. For instance, it can modulate pathways involved in resistance, thereby making chemotherapy more effective.

Furthermore, pterostilbene targets cancer stem cells (CSCs). CSCs are a subpopulation of cancer cells responsible for tumor initiation, recurrence, and metastasis. They are often more resistant to standard treatments. Pterostilbene has demonstrated the ability to inhibit the self-renewal capacity of CSCs and suppress their gene expression, offering a strategy to potentially prevent cancer recurrence.

In combination therapies, pterostilbene can synergize with existing cancer treatments. Preclinical studies indicate that pterostilbene can enhance the cytotoxic effects of chemotherapy drugs like 5-fluorouracil in colon cancer cells, making the treatment more potent. It can also modulate signaling pathways that are critical for cancer cell survival and growth, thereby improving the overall outcome of combined therapeutic approaches.

The superior bioavailability and favorable safety profile of pterostilbene compared to resveratrol further enhance its appeal as a therapeutic adjunct. By offering multifaceted support—from direct cytotoxic effects and apoptosis induction to overcoming resistance and targeting CSCs—pterostilbene represents a promising natural compound that can significantly enhance the efficacy of current cancer treatment modalities and provide new avenues for tackling this complex disease.