Bioactive Compounds and Anticancer Mechanisms

Bioactive compounds derived from plants, fungi and microorganisms encompass a diverse array of alkaloids, phenolics, terpenoids and sterols that exert selective cytotoxic effects on malignant cells. Central to their anticancer action is the induction of programmed cell death, primarily via intrinsic and extrinsic apoptotic pathways that converge on caspase activation and mitochondrial dysfunction. Many of these compounds also perturb cellular redox balance by generating reactive oxygen species (ROS), triggering mitochondrial membrane depolarisation and promoting autophagic processes that can either enhance or attenuate apoptosis. In addition, modulation of cell‐cycle regulators, inhibition of pro‐survival kinases (for example PI3K/AKT and STAT3), suppression of angiogenesis and interference with metastasis‐associated signalling underpin the multi-faceted therapeutic potential of natural products. Recent advances in chemical synthesis, conjugation to targeting moieties and combination regimens with established chemotherapeutics have elevated several bioactive natural scaffolds towards clinical evaluation. Collectively, this body of work underscores the global significance of natural-product-inspired drug discovery and offers tangible lead candidates for more selective and less toxic anticancer therapies.

Research from Nature Portfolio

One foundational study elucidated the anticancer properties of ergosterol peroxide isolated from a marine fungus, demonstrating potent inhibition of human lung adenocarcinoma cell viability through ROS‐dependent mitochondrial apoptosis. The work revealed that peroxide bridges within the sterol scaffold initiate caspase‐mediated cell death, while concurrently inducing a protective autophagic response. Detailed proteomic analysis further showed downregulation of survival-promoting kinases (AKT1, mTOR, NF-κB) and induction of stress-activated kinases (p38α, JNK), highlighting a network of signalling events that can be exploited for synergistic combinations with kinase inhibitors and conventional drugs.

Research from all publishers

In 2023, a study on Calvatia nipponica mushroom fruiting bodies led to the isolation of N,N-dimethyl-anthranilic acid, which exhibited selective cytotoxicity against MDA-MB-231 breast cancer cells. Mechanistic investigations revealed activation of both extrinsic (caspase-8) and intrinsic (caspase-9, BAX/Bcl-2 modulation) apoptotic cascades, resulting in PARP cleavage and significant apoptotic indices.

A 2020 synthetic chemistry effort produced novel steroidal 5α,8α-endoperoxide derivatives bearing semicarbazone side chains. One lead compound triggered mitochondrial membrane depolarisation in HepG2 cells, upregulated pro-apoptotic Bax, downregulated Bcl-2, generated ROS and activated the full caspase cascade, underscoring the utility of endoperoxide moieties in apoptosis induction.

Another investigation explored ergosterol peroxide purified from Paecilomyces cicadae fermentation broth and demonstrated growth inhibition, migration and invasion suppression of renal cell carcinoma lines. The compound induced G2/M cell‐cycle arrest, attenuated β-catenin signalling and promoted apoptosis in a dose-dependent manner, establishing a robust preclinical rationale for further in vivo evaluation.

Bioactive Compounds and Anticancer Mechanisms publication trend

The graph below shows the total number of articles in bioactive compounds and anticancer mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Apoptosis: Programmed cell death characterised by caspase activation, DNA fragmentation and membrane blebbing.

Autophagy: Lysosome-mediated degradation of cellular components that can modulate cell survival or death.

Reactive oxygen species (ROS): Chemically reactive molecules derived from oxygen that can induce oxidative stress and trigger cell‐death pathways.

Caspase: A family of cysteine proteases that orchestrate apoptotic signalling and execution.

Bcl-2 family proteins: Regulators of mitochondrial outer membrane permeability that determine cell fate by balancing pro- and anti-apoptotic signals.

Endoperoxide: A peroxide bridge within a cyclic structure that often generates ROS upon cleavage, promoting anticancer activity.

References

1. N,N-Dimethyl-anthranilic Acid from Calvatia nipponica Mushroom Fruiting Bodies Induces Apoptotic Effects on MDA-MB-231 Human Breast Cancer Cells. Nutrients (2023).
2. Ergosterol peroxide from marine fungus Phoma sp. induces ROS-dependent apoptosis and autophagy in human lung adenocarcinoma cells. Scientific Reports (2018).
3. Novel Steroidal 5α,8α-Endoperoxide Derivatives with Semicarbazone/Thiosemicarbazone Side-chain as Apoptotic Inducers through an Intrinsic Apoptosis Pathway: Design, Synthesis and Biological Studies. Molecules (2020).
4. Anticancer Action and Mechanism of Ergosterol Peroxide from Paecilomyces cicadae Fermentation Broth. International Journal of Molecular Sciences (2018).