Journal of Plant Biochemistry and Biotechnology

, Volume 26, Issue 4, pp 451–466 | Cite as

Towards the mode of action of Strobilanthes crispus through integrated computational and experimental analyses

  • Kah Keng Wong
  • Lewis H. Mervin
  • Angelica Mazzolari
  • Andreas Bender
  • Nik Soriani Yaacob
Original Article


Bioactive sub-fractions from the tropical herbal plant Strobilanthes crispus (S. crispus) has been shown to induce apoptosis of breast cancer cells in vitro and reduce tumor size in vivo by our earlier studies. We have recently isolated five major compounds from S. crispus sub-fraction, namely lutein, β-sitosterol, campesterol, stigmasterol and pheophytin a. In this study, we set out to investigate each compound’s protein targets and mechanism of action through prediction of protein targets via a ligand-based target prediction protocol, Prediction IncluDinG INactives, and radioligand binding assays. The three phytosterol molecules (β-sitosterol, campesterol, stigmasterol) showed enrichment of hormone signaling GO terms [average ratio (AR) <0.01], while the SMAD signaling pathway was associated with pheophytin a (AR < 0.01). GO terms associated with retinoic acid receptor (RAR) and retinoid X receptor (RXR) were distinctly represented by protein targets of lutein (AR < 0.01). All members of the RAR/RXR family of proteins were predicted to be targeted by lutein, a feature that was not present in the other four S. crispus-derived compounds. Radioligand binding assay in vitro validated that lutein showed higher binding affinity with RXRα (IC50: 5.74 µM; Ki: 4.55 µM) than RARα (IC50: 25.1 µM; Ki: 14 µM). Molecular docking analysis demonstrated that lutein could occupy a large hydrophobic cavity of the hRXRα-LBP crystal structure mainly through hydrophobic interactions with leucine and isoleucine residues, and also hydrogen bond between a hydroxyl group of lutein with Glu239. Our findings suggest that lutein-RXRα interaction might play a role in the anti-breast cancer effects rendered by S. crispus.


Strobilanthes crispus PIDGIN Phytosterol Pheophytin a Lutein RAR/RXR 



Prediction IncluDinG INactives


Retinoic acid receptor alpha


Retinoid X receptor alpha



This work was supported by Universiti Sains Malaysia research (1001/PPSP/853002) and travel grants (1001/JPNP/AUPRM006) awarded to NSY and KKW, respectively. LHM would like to thank BBSRC and AstraZeneca, and for their funding.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

13562_2017_407_MOESM1_ESM.docx (153 kb)
Supplementary material 1 (DOCX 153 kb)


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© Society for Plant Biochemistry and Biotechnology 2017

Authors and Affiliations

  1. 1.Department of Immunology, School of Medical SciencesUniversiti Sains MalaysiaKubang KerianMalaysia
  2. 2.Department of Chemistry, Centre for Molecular InformaticsUniversity of CambridgeCambridgeUK
  3. 3.Department of Pharmaceutical SciencesUniversità degli Studi di MilanoMilanoItaly
  4. 4.Department of Chemical Pathology, School of Medical SciencesUniversiti Sains MalaysiaKubang KerianMalaysia

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