New Cancer Inhibitor Candidate: Quercetin from Ciplukan Revealed Through Bioinformatics Analysis
Discover how computational biology uncovers the molecular mechanisms behind traditional medicinal plant's anticancer properties
The Global Cancer Burden and New Hope from Nature
The world faces an increasingly alarming cancer burden. Data from the World Health Organization (WHO) in 2024 recorded more than 20 million new cancer cases worldwide, with mortality reaching 9.7 million lives. In Indonesia, cancer remains one of the leading causes of death after heart disease and stroke 4 .
Amid these challenges, scientists continue to explore the potential of natural compounds as new weapons against cancer. One promising hope comes from a wild plant that we might often overlook—ciplukan (Physalis angulata). This plant has been traditionally used in natural medicine, including for cancer, but its molecular mechanisms have remained a mystery until now 1 .
Traditional Knowledge Meets Modern Science
Bioinformatics bridges traditional medicinal knowledge with modern scientific validation
Ciplukan: The Small Plant with Big Benefits
Ciplukan (Physalis angulata) is a plant that grows widely in Southeast Asia, including Indonesia. Although often considered a wild plant, ciplukan actually holds extraordinary medicinal potential. In traditional medicine practice, this plant has been used to treat various diseases, including as an anticancer agent 1 .
What makes ciplukan special in cancer research is its content of bioactive compounds, especially quercetin. Quercetin belongs to the flavonoid group—a type of polyphenol found in various fruits and vegetables like apples, onions, berries, and tea. The average flavonoid intake in our diet reaches 1-2 grams per day, depending on the type and amount of fruits, vegetables, or beverages consumed 7 .
Quercetin's Anticancer Mechanisms
Ciplukan (Physalis angulata) plant
Quercetin molecular structure
Quercetin's Proven Efficacy
Quercetin has been shown to induce apoptosis in nine different cancer cell types tested, including colon cancer CT-26, prostate cancer LNCaP, breast cancer MCF-7, leukemia MOLT-4-T, and ovarian cancer CHO cell lines 7 .
Bioinformatics: Bridging Traditional Medicine and Modern Science
Bioinformatics is a scientific field that combines biology, computer science, and information technology to analyze biological data on a large scale. In drug research, bioinformatics enables scientists to predict interactions between potential drug compounds and target proteins in the body without having to conduct expensive and time-consuming laboratory experiments 1 .
Biological Data
Protein structures, genomic sequences, metabolic pathways
Computational Analysis
Algorithms, simulations, data mining, pattern recognition
Drug Discovery
Molecular docking, virtual screening, ADMET prediction
Molecular Docking: The Key Technique
One of the most widely used bioinformatics techniques in drug discovery is molecular docking. This technique allows researchers to:
- Predict how a small molecule binds to a protein target
- Calculate binding strength (affinity)
- Identify specific atoms and amino acid residues involved
- Screen natural compounds efficiently
This approach is highly effective for screening natural compounds with potential as drugs, as it can be performed computationally before further experimental validation 1 2 .
Peeking into the Key Experiment: Quercetin vs. Cancer Proteins
A study conducted in 2018 took a bioinformatics approach to examine the molecular interactions of quercetin from ciplukan leaf extract with cancer proteins. This research specifically aimed to understand the mechanisms of cancer cell inhibition by quercetin at the molecular level 1 .
Methodology: Step by Step
Protein Target Preparation
Cancer proteins ERK2 and PDK1 were selected as targets. ERK2 plays a role in maintaining continuous proliferation ability by cancer cells, while PDK1 prevents cancer cells from undergoing apoptosis 1 .
Ligand Preparation
Quercetin compound (specifically 3-O-methylquercetin) found in ciplukan leaf extract was prepared in 3D format for docking simulation.
Molecular Docking Simulation
The docking process was performed using specialized software to predict how quercetin binds to protein targets.
Interaction Analysis
Docking results were analyzed to determine binding strength (affinity) and specific amino acid residues involved in the interaction.
Results and Analysis: Promising Findings
The research results showed that 3-O-methylquercetin, one form of quercetin in ciplukan, has equivalent affinity values to tested inhibitors that block cancer proteins ERK2 and PDK1. This indicates that quercetin has the potential to inhibit both cancer proteins 1 .
| Protein Target | Function in Cancer | Quercetin Binding Affinity | Remarks |
|---|---|---|---|
| ERK2 | Maintains cancer cell proliferation | Equivalent to available inhibitors | Inhibits proliferation signals |
| PDK1 | Prevents cancer cell apoptosis | Equivalent to available inhibitors | Promotes cancer cell death |
| Uridine 5-monophosphate synthase | Pyrimidine synthesis for cancer growth | -8.28617 kcal/mol 2 | Other potential target |
ERK2 Inhibition
Quercetin disrupts proliferation signals that cause cancer cells to keep dividing.
PDK1 Inhibition
Quercetin removes apoptosis barriers allowing cancer cells to undergo programmed cell death.
| Protein Target | Amino Acid Residues Interacting | Interaction Type |
|---|---|---|
| Uridine 5-monophosphate synthase 2 | Tyr 432, Gly 450 | Hydrogen bonds (2) |
| Uridine 5-monophosphate synthase 2 | Asn 312, Met 371, Pro 417 | Hydrophobic interactions |
| Proto-oncogene protein-tyrosine kinase 2 | Various active residues | Hydrogen and hydrophobic bonds |
These findings are consistent with previous research showing that quercetin indeed has activity on various receptor targets including proto-oncogene protein-tyrosine kinase and uridine 5-monophosphate synthase 2 .
Researcher's Toolkit: Bioinformatics Tools for Anticancer Research
In bioinformatics research to discover anticancer drugs from natural compounds, various specialized tools and resources are used. Here are some important tools that form the modern researcher's "toolkit":
| Tool/Resource | Function | Example in Ciplukan Research |
|---|---|---|
| Molecular Docking Software | Predicts how ligands bind to protein targets | AutoDock Vina and similar for quercetin-ERK2/PDK1 simulation 1 |
| Protein Data Bank (PDB) | Storage of 3D protein structures | Accessing ERK2 and PDK1 structures for simulation 1 |
| PharmMapper Server | Identifies potential targets of drug compounds | Identifying uridine 5-monophosphate synthase as quercetin target 2 |
| Visualization Tools | Analyzes molecular interactions | LIGPLOT for schematic diagrams of protein-ligand interactions 2 |
| Natural Compound Databases | Collection of bioactive compounds from plants | Identifying quercetin and its derivatives in ciplukan |
3D Structure Analysis
Visualizing molecular interactions in three dimensions for precise binding analysis.
Pathway Mapping
Identifying how compounds affect complex biological pathways in cancer cells.
Data Integration
Combining multiple data sources for comprehensive analysis of compound effects.
Implications and Applications: From Computer Screen to Patient Bedside
The findings of this research have important implications for the development of cancer drugs in the future:
Basis for More Targeted Therapy
By knowing the specific proteins inhibited by quercetin, scientists can design drugs that are more precisely targeted. This approach allows for more effective therapy with minimal side effects, as it primarily targets cancer cells without extensively damaging healthy cells 1 .
Validating Traditional Medicine
This research provides a scientific basis for the traditional use of ciplukan in cancer treatment. By understanding the molecular mechanisms underlying its anticancer effects, we can optimize the use of this plant more rationally and measurably 4 .
Development of Standardized Herbal Medicine
Indonesia has great potential in the development of herbal medicine. With more than 30,000 plant species and 9,600 of them having medicinal properties, the natural wealth of the archipelago should become a source of economic and health strength based on local wisdom 5 . However, currently only about 71 herbs have become standardized herbal medicines (OHT) and 20 herbs have phytopharmacal status 5 .
Safe Complementary Therapy
Experts emphasize that herbs are not replacements for medical therapy, but rather as companions. Cancer treatment must remain comprehensive according to doctor's recommendations. Herbs can be consumed with a 2-3 hour interval after patients take medical drugs, so their benefits are complementary 4 .
"Natural ingredients can be one of the answers because many studies show that herbs can help prevent as well as alleviate cancer" - Dr. apt. Rifki Febriansah, M.Sc. from Universitas Muhammadiyah Yogyakarta 4 .
Conclusion: The Future of Nature-Based Cancer Research Enhanced by Technology
Research combining the potential of natural compounds like quercetin from ciplukan with bioinformatics approaches has opened a promising new path in the war against cancer. Not only providing scientific validation for traditional medicine, this approach also provides a roadmap for the development of more targeted and effective cancer drugs.
Natural Wealth
Indonesia's biodiversity offers immense potential for drug discovery
Computational Power
Bioinformatics accelerates and refines the drug discovery process
Global Potential
Indonesia could become a major player in global herbal medicine development
With Indonesia's abundant natural wealth, research support, and strong regulations, Indonesia has the potential to become a major player in the development of world herbal medicine, on par with Korea famous for its ginseng, or China with its traditional medicine 5 .
With the spirit of collaboration between modern science and traditional wisdom, the future of the war against cancer appears increasingly bright.
This article was compiled based on research results published in scientific journals and academic repositories to ensure information accuracy.