Therapeutic potential of α-santalol: Sources, mechanisms, and anti-tumor prospects

Α-santalol, a naturally occurring sesquiterpene and a primary constituent of sandalwood oil, exhibits significant potential as an antitumor agent due to its diverse biological activities. Derived mainly from Santalum species like Santalum album, this compound has garnered attention for its profound effects on cancer prevention and treatment. Its anticancer properties are attributed to its ability to regulate cell cycle progression, induce apoptosis, and modulate key signaling pathways, including PI3K/Akt/mTOR and Wnt/β-catenin. Preclinical studies demonstrate α-santalol's efficacy in inhibiting various cancer cell lines such as breast, prostate, skin, and liver cancers, alongside its relatively lower toxicity to normal cells. In vitro and in vivo investigations reveal that α-santalol induces G2/M phase arrest, promotes apoptosis through intrinsic and extrinsic pathways, and suppresses tumor growth by targeting angiogenesis-related pathways. Furthermore, innovative delivery systems, such as chitosan nanoparticles, have enhanced its bioavailability, ensuring higher therapeutic efficacy with minimal systemic side effects. Studies on localized transdermal delivery also highlight its suitability for chemoprevention, particularly in high-risk cohorts. The synergistic potential of α-santalol when combined with other chemotherapeutic agents offers a promising avenue to reduce resistance mechanisms and enhance therapeutic outcomes. Nonetheless, challenges such as limited bioavailability and the need for robust clinical trials hinder its translation into standard care. Future research should prioritize optimizing delivery systems, designing well-structured clinical trials, and exploring interdisciplinary approaches for industrial scalability and applications in therapeutic and preventive oncology. α-santalol's potential in being an effective, low-toxicity, and sustainable cancer treatment underscores its value for further biomedical research and commercial development.