β-Carboline Alkaloids in Cancer Therapeutics

β-Carboline alkaloids constitute a diverse class of naturally occurring indole alkaloids found in plants such as Peganum harmala and Banisteriopsis caapi, exhibiting a broad spectrum of biological activities. In the context of oncology, these compounds have attracted attention for their ability to engage multiple anticancer mechanisms, including induction of programmed cell death, disruption of cell cycle progression, inhibition of pro-survival signalling pathways and suppression of tumour angiogenesis. Structural modification and hybridisation strategies have yielded derivatives with enhanced potency, improved selectivity and reduced toxicity profiles, demonstrating activity against a range of cancer cell types in vitro and in vivo. Advances in synthetic chemistry have also enabled the design of β-carboline scaffolds able to overcome drug resistance and synergise with existing chemotherapeutics. Collectively, this body of work underlines the global significance of β-carboline alkaloids as versatile scaffolds for the development of novel anticancer agents.

Research from Nature Portfolio

Recent studies have expanded the repertoire of β-carboline derivatives with pronounced antitumour effects. A series of N2-benzylated harmine analogues demonstrated low micromolar activity against gastric, melanoma and colorectal carcinoma cell lines, triggering apoptosis through suppression of the PI3K/AKT axis and elevation of reactive oxygen species, and achieving significant tumour growth inhibition in xenograft models with minimal effects on normal tissues. Parallel efforts yielded hybrids of the β-carboline core and salicylic acid, which exhibited superior antiproliferative potency compared with standard agents; these hybrids selectively induced mitochondrial-mediated apoptosis by up-regulating pro-apoptotic Bax, down-regulating Bcl-2 and activating the caspase cascade. In a complementary approach, natural harmaline was shown to arrest cancer cells in G2/M phase via up-regulation of Fas/FasL and activation of caspase-8 and caspase-3, with corroborating antitumour efficacy in animal models.

β-Carboline Alkaloids in Cancer Therapeutics publication trend

The graph below shows the total number of articles in β-carboline alkaloids in cancer therapeutics across all publications each year (not limited to Nature Index journals).

Technical terms

Apoptosis: Programmed cell death mediated by caspase enzymes, ensuring controlled removal of damaged or unwanted cells.

Cell cycle arrest: Pausing of cell division at defined checkpoints to prevent propagation of genomic damage.

Angiogenesis: Formation of new blood vessels from pre-existing vasculature, a process exploited by tumours to obtain oxygen and nutrients.

PI3K/AKT pathway: Intracellular signalling cascade promoting cell survival and proliferation, frequently hyperactivated in cancers.

Reactive oxygen species: Highly reactive oxygen-containing molecules that can damage cellular components or function as secondary messengers in apoptotic pathways.

Polo-like kinases (PLKs): Family of serine/threonine kinases central to mitotic entry and progression, representing attractive targets for anticancer intervention.

References

1. Pharmacological and therapeutic effects of Peganum harmala and its main alkaloids. Pharmacognosy Reviews (2013).
2. Synthesis and mechanisms of action of novel harmine derivatives as potential antitumor agents. Scientific Reports (2016).
3. Design, synthesis and biological evaluation of hybrids of β-carboline and salicylic acid as potential anticancer and apoptosis inducing agents. Scientific Reports (2016).
4. Novel mechanism of harmaline on inducing G2/M cell cycle arrest and apoptosis by up-regulating Fas/FasL in SGC-7901 cells. Scientific Reports (2015).
5. The Role of Ayahuasca in Colorectal Adenocarcinoma Cell Survival, Proliferation and Oxidative Stress. Pharmaceuticals (2024).
6. A Natural Small Molecule Harmine Inhibits Angiogenesis and Suppresses Tumour Growth through Activation of p53 in Endothelial Cells. PLOS ONE (2012).
7. A Series of Beta-Carboline Derivatives Inhibit the Kinase Activity of PLKs. PLOS ONE (2012).