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A topic from the subject of Biochemistry in Chemistry.

  • 11 months ago
  • 9 min read
Biochemistry of Cancer
Introduction

Cancer is a complex disease resulting from the uncontrolled growth and proliferation of abnormal cells. Unlike normal cells, which have a limited lifespan and undergo regulated cell division, cancer cells have acquired the ability to bypass these controls and continue dividing indefinitely.

Basic Concepts

Understanding the biochemical basis of cancer requires grasping several basic concepts:

  • Oncogenes: Oncogenes are mutated genes that promote uncontrolled cell growth and division. These mutations can activate proto-oncogenes (normal genes involved in cell growth) or inactivate tumor suppressor genes (which normally prevent uncontrolled cell division).
  • Tumor Suppressor Genes: Tumor suppressor genes inhibit cell growth and division. Mutations inactivating these genes allow cancer cells to escape controls and continue dividing.
  • Cell Cycle: The cell cycle is the process of cell division. Cancer cells have cell cycle defects that allow them to bypass checkpoints preventing damaged cell proliferation.
  • Metastasis: Metastasis is the spread of cancer cells from their primary site to other body parts. Cancer cells metastasize through the bloodstream or lymphatic system.
Equipment and Techniques

Studying cancer biochemistry requires specialized equipment and techniques, including:

  • Spectrophotometry: Measures light absorption or emission by a sample to study the concentration of molecules (DNA, RNA, proteins) in cancer cells.
  • Gel Electrophoresis: Separates molecules based on size and charge to study gene expression in cancer cells or identify genetic mutations.
  • Mass Spectrometry: Identifies and quantifies molecules based on their mass-to-charge ratio to characterize proteins and other molecules involved in cancer.
Types of Experiments

Many experiments study cancer biochemistry. Common types include:

  • Gene Expression Analysis: Studies gene expression in cancer cells to identify genes involved in cancer development and progression.
  • Protein Analysis: Studies protein expression and activity in cancer cells to identify potential cancer therapy targets.
  • Metabolic Analysis: Studies cancer cell metabolism to identify metabolic pathways essential for cancer cell growth and proliferation.
Data Analysis

After collecting data from cancer biochemistry experiments, it's crucial to analyze it to identify patterns and trends. Statistical methods are often used to identify differentially expressed genes and proteins, essential metabolic pathways for cancer cell growth, and potential cancer therapy targets.

Applications

Cancer biochemistry has led to new diagnostic and therapeutic strategies. Applications include:

  • Identification of Biomarkers: Cancer biomarkers (molecules detected in blood or other body fluids) are indicative of cancer and used for early detection, diagnosis, and monitoring.
  • Development of Targeted Therapies: Targeted therapies are drugs inhibiting specific molecules involved in cancer development and progression. They are highly effective in treating certain cancers.
  • Development of Immunotherapies: Immunotherapies stimulate the immune system to attack cancer cells and show promise in treating various cancers.
Conclusion

The study of cancer biochemistry has significantly contributed to our understanding of cancer development and progression, leading to new diagnostic and therapeutic strategies. Further advancements in cancer biochemistry will likely lead to even greater progress in cancer treatment and prevention.

Biochemistry of Cancer

Cancer is a complex disease characterized by the uncontrolled growth and spread of abnormal cells in the body. The biochemistry of cancer involves alterations in cellular processes that promote the development and progression of tumors. These alterations affect various aspects of cellular function, leading to the hallmarks of cancer.

Key Points:

  • Altered Metabolism: Cancer cells often exhibit increased glucose uptake and lactate production, even in the presence of oxygen (Warburg effect). This metabolic shift, characterized by aerobic glycolysis, supports the rapid growth and proliferation of cancer cells. It provides building blocks for biosynthesis and energy, albeit inefficiently compared to oxidative phosphorylation.
  • Dysregulation of Cell Cycle: Cancer cells evade normal cell cycle checkpoints, leading to uncontrolled cell division. Mutations in genes encoding proteins involved in cell cycle regulation (e.g., p53, Rb, cyclin-dependent kinases, and their inhibitors) can contribute to this dysregulation. This results in uncontrolled proliferation and genomic instability.
  • Oncogenes and Tumor Suppressor Genes: Oncogenes are mutated genes that promote cancer growth, often through increased signaling activity. Tumor suppressor genes normally inhibit cell growth and proliferation; their inactivation removes this brake on cell division. Mutations that activate oncogenes or inactivate tumor suppressor genes can disrupt normal cellular signaling pathways and contribute to cancer formation. Examples include RAS oncogenes and p53 tumor suppressor gene.
  • Angiogenesis: Cancer cells promote the formation of new blood vessels (angiogenesis) to supply nutrients and oxygen to the growing tumor. This process is driven by the secretion of growth factors, such as vascular endothelial growth factor (VEGF), and other angiogenic factors. Inhibition of angiogenesis is a common cancer therapeutic strategy.
  • Immune Evasion: Cancer cells often evade the immune system, allowing them to proliferate and escape detection. They can express molecules that suppress immune responses or manipulate the immune microenvironment to avoid immune cell attack. Immunotherapy aims to harness the power of the immune system to fight cancer.
  • Metastasis: The spread of cancer cells from the primary tumor to distant sites in the body is a critical aspect of cancer progression. This involves complex processes including cell detachment, invasion of surrounding tissues, intravasation (entry into blood vessels), extravasation (exit from blood vessels), and colonization of new sites.
  • Genomic Instability: Cancer cells often exhibit high rates of mutations and chromosomal abnormalities. This genomic instability contributes to the evolution of cancer cells, allowing them to acquire traits that promote growth, survival, and metastasis.

Conclusion:

Understanding the biochemistry of cancer provides crucial insights into the molecular mechanisms underlying tumor development and progression. Targeting these altered biochemical pathways through therapies, such as chemotherapy, targeted therapy, and immunotherapy, represents a promising approach for the treatment and prevention of cancer. Continued research into the intricate biochemical processes involved in cancer is essential for developing more effective and personalized cancer treatments.

Experiment: Warburg Effect in Cancer Cells
Objective:

To demonstrate the increased glucose uptake and lactate production in cancer cells compared to normal cells.

Materials:
  • Cancer cell line (e.g., HeLa cells)
  • Normal cell line (e.g., MRC-5 cells)
  • Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS)
  • 2-deoxyglucose (2-DG)
  • Lactate dehydrogenase (LDH) assay kit
  • Spectrophotometer
  • Phosphate-buffered saline (PBS)
  • Cell culture incubator
  • Centrifuge
  • Sonicator
  • Protein assay kit (e.g., Bradford assay)
Procedure:
  1. Culture both cancer and normal cells in DMEM with 10% FBS in a cell culture incubator at 37°C and 5% CO2 for 24 hours.
  2. Prepare two groups for each cell type: a control group and a 2-DG treated group.
  3. Treat the 2-DG treated groups with 1 mM 2-DG for 1 hour.
  4. Harvest cells by centrifugation (e.g., 1000g for 5 minutes).
  5. Wash the cell pellets twice with cold PBS.
  6. Resuspend cells in PBS and lyse them using a sonicator.
  7. Centrifuge the lysate (e.g., 10,000g for 10 minutes) and collect the supernatant.
  8. Measure the protein concentration of the supernatant using a protein assay kit (e.g., Bradford assay) following the manufacturer's instructions. This step is crucial for normalizing LDH activity.
  9. Perform the LDH assay according to the manufacturer's instructions using the collected supernatants. Measure the absorbance at the specified wavelength using a spectrophotometer.
  10. Calculate lactate production based on the LDH assay results and normalize to protein concentration.
Key Procedures:

Inhibition of glucose uptake: 2-DG is a glucose analog that inhibits glucose uptake into cells by competing with glucose for the glucose transporter. By treating cells with 2-DG, we can estimate the difference in glucose uptake between cancer and normal cells. Reduced lactate production in the 2-DG treated group indicates successful inhibition.

Lactate dehydrogenase (LDH) assay: LDH is an enzyme that catalyzes the conversion of pyruvate to lactate. By measuring LDH activity, we can quantify lactate production, a marker of anaerobic glycolysis.

Significance:

The Warburg effect is a fundamental metabolic shift observed in cancer cells. This experiment demonstrates that cancer cells exhibit increased glucose uptake and lactate production compared to normal cells, even in the presence of oxygen (aerobic glycolysis). This metabolic adaptation promotes rapid cell proliferation and supports the growth and survival of cancer cells even under hypoxic conditions. Understanding the biochemistry of cancer can lead to the development of targeted therapies aimed at disrupting these metabolic pathways, such as inhibiting glucose transporters or targeting LDH.

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