Abstract

Cancer remains one of the leading causes of morbidity and mortality worldwide, despite substantial advances in diagnosis and therapy. Conventional treatment modalities such as chemotherapy, radiotherapy, and targeted therapy often face limitations including drug resistance, toxicity, and high costs. In recent years, natural bioactive compounds derived from plants, marine organisms, and microbes have garnered significant attention as promising alternatives or adjuncts in cancer management. These compounds—encompassing flavonoids, alkaloids, terpenoids, polyphenols, and others—exhibit a broad spectrum of anticancer activities through diverse mechanisms, including induction of apoptosis, inhibition of angiogenesis, modulation of oxidative stress, immune regulation, and suppression of key oncogenic signaling pathways such as PI3K/Akt, NF-κB, and MAPK. Additionally, many bioactive compounds have demonstrated potential in overcoming multidrug resistance and sensitizing tumors to conventional chemotherapeutics. This review critically evaluates the current evidence on the anticancer properties of major classes of natural bioactive compounds, highlighting their molecular mechanisms of action, therapeutic potential, and pharmacological relevance. Special attention is given to recent advancements in nanoformulation and drug delivery systems that enhance bioavailability and target specificity. Furthermore, the review explores the challenges and opportunities in translating preclinical successes into clinical applications, including regulatory hurdles, standardization, and toxicity profiling. By integrating insights from molecular oncology, pharmacognosy, and translational research, this review underscores the potential of natural bioactive compounds as key players in the development of safer, more effective, and sustainable cancer therapies. Future directions are proposed to accelerate the clinical development of these compounds, paving the way for novel, integrative approaches in cancer treatment and prevention.

Key words: Natural bioactive compounds, Cancer therapy, Apoptosis, Multidrug resistance, Oncogenic signaling pathways, Nanoformulation, Chemoprevention, Translational oncology