Himalayan Plant Compounds Show Dual Action Against Lung and Prostate Cancer Cells

Two natural compounds extracted from medicinal plants of the Himalayan region have shown potent activity against lung and prostate cancer cells in laboratory tests, according to a new study published in Frontiers in Pharmacology. Researchers at Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir, working with a collaborator at the University of Tabuk, isolated atisine and linoleic acid from the tuberous roots of Aconitum heterophyllum and podophyllotoxin from the fruits of Podophyllum hexandrum, then evaluated their ability to attack two molecular targets linked to cancer progression: the interleukin-1 receptor type 1 (IL-1R1) and the androgen receptor (AR). The rationale behind the dual-target approach rests on the biology of the two diseases.

IL-1R1 drives chronic inflammation, tumour survival and metastasis, processes that fuel cancer progression in lung tissue, while androgen receptor signalling is the central engine of prostate cancer growth and a well-known source of therapeutic resistance when blocked by existing drugs. Simultaneously modulating an inflammatory pathway and a hormone-dependent pathway could, in principle, make it harder for tumours to adapt and escape treatment. The team began with classical phytochemistry.

Plant material was extracted using Soxhlet apparatus, and individual compounds were separated by thin-layer chromatography followed by column chromatography. The purified molecules were then tested for cytotoxicity and long-term antiproliferative effects in two widely used cancer cell lines: A549, derived from lung adenocarcinoma, and LNCaP, derived from prostate cancer. The cytotoxicity results were striking for one compound in particular.

Podophyllotoxin, a well-known aryltetralin lignan, recorded an IC₅₀ value of 0.04 micromolar in both A549 and LNCaP cells, a potency that exceeded that of doxorubicin, a standard chemotherapeutic agent used as a comparator in the assays. Atisine, a diterpenoid alkaloid from Aconitum heterophyllum, showed moderate activity with IC₅₀ values between 2.1 and 2.3 micromolar across the two cell lines. Linoleic acid, by contrast, displayed only weak anticancer activity, requiring concentrations around 100 micromolar to reach half-maximal effect.

Short-term killing of cancer cells does not necessarily translate into lasting tumour control, so the researchers also ran colony formation assays, which measure whether treated cells retain the ability to divide repeatedly and establish new colonies. These experiments confirmed strong suppression of clonogenic survival by podophyllotoxin and a moderate inhibitory effect by atisine, reinforcing the pattern seen in the acute cytotoxicity tests. On the computational side, the team docked the compounds into the crystal structures of IL-1R1 (PDB entry 1ITB) and the androgen receptor (PDB entry 2YHD).

The docking scores ranged from −8.1 to −5.9 kilocalories per mole, indicating favourable predicted binding at both targets. To test whether these predicted complexes would remain stable under more realistic physical conditions, the researchers ran 100-nanosecond molecular dynamics simulations and calculated binding free energies using the MM-GBSA method. The simulations showed stable protein–ligand complexes with low root-mean-square deviation fluctuations, suggesting the docked poses were not computational artefacts but energetically sustainable arrangements.

Pharmacokinetic plausibility was assessed through ADMET profiling, which evaluates absorption, distribution, metabolism, excretion and toxicity in silico. Both atisine and podophyllotoxin passed with favourable drug-likeness characteristics, an early but necessary filter for any molecule hoping to progress toward drug development. Linoleic acid, already limited by its weak cytotoxicity, did not emerge as a lead candidate in this study.

Because single-target thinking often fails in cancer, the researchers also applied network pharmacology, a method that maps all plausible protein targets of a compound against disease-associated gene networks. This analysis identified 133 intersecting targets shared between the compounds and cancer-related pathways. Hub genes at the centre of the network included SRC, EGFR and AKT1, and pathway enrichment analysis highlighted the PI3K-Akt signalling cascade, one of the most frequently dysregulated survival pathways in human cancer, along with other cancer-related signalling routes.

The authors are careful to frame the work as preliminary. The cell-line experiments establish potency and clonogenic suppression, while the docking, dynamics and network analyses generate hypotheses about mechanism at IL-1R1, AR and downstream hubs such as EGFR and AKT1. What the study does not yet provide is direct experimental validation of target engagement in cells or animals, pharmacokinetic behaviour in vivo, or safety margins beyond computational prediction.

The researchers themselves state that the findings provide a foundation for further optimisation and in vivo validation rather than a therapeutic claim. Even so, the combination of nanomolar-range cytotoxicity from podophyllotoxin, moderate activity from atisine, stable predicted binding to both IL-1R1 and the androgen receptor, and a coherent multitarget network signature makes this integrated screening pipeline a template worth watching. The next steps, target-level confirmation and animal studies, will determine whether these Himalayan natural products can move from the bench toward meaningful dual-action anticancer agents.

Subject of Research: Natural compounds from Aconitum heterophyllum and Podophyllum hexandrum targeting IL-1R1 and the androgen receptor in lung and prostate cancer models

Article Title: Targeting IL-1R1 and androgen receptor using natural compounds from Aconitum heterophyllum and Podophyllum hexandrum: an in silico and in vitro study

Article References: Un Nisa, D. M., Sofi, P. A., Peerzada, I. A., Mir, R., & Bhat, T. B. (2026). Targeting IL-1R1 and Androgen Receptor Using Natural Compounds from Aconitum heterophyllum and Podophyllum hexandrum: An In Silico and In Vitro Study. Frontiers in Pharmacology, 17, 1909943. https://doi.org/10.3389/fphar.2026.1909943

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1909943

Keywords: podophyllotoxin, atisine, Aconitum heterophyllum, Podophyllum hexandrum, IL-1R1, androgen receptor, lung cancer, prostate cancer, molecular docking, molecular dynamics, network pharmacology, natural products