Induction of apoptosis in breast cancer cells by naphthylisoquinoline alkaloids
Prem Prakash Kushwaha1, Atul Kumar Singh1, Kumari Sunita Prajapati1
1Department of Biochemistry, Central University of Punjab, Bathinda 151401, Punjab, India.
Abstract:
Breast cancer is one of the most common types of cancer in the world and a major cause of mortality. Present therapeutic strategies against breast cancer have severe drawbacks such as allergies, damage to healthy tissues, reoccurrence of cancer, and emergence of drug resistance. Naphthylisoquinoline alkaloids are a group of structurally unique natural products produced by tropical lianas belonging to the plant families Dioncophyllaceae and Ancistrocladaceae indigenous to Asia and Africa. These secondary metabolites have been reported to show anti-infective activity, but they also act against leukemic and pancreatic cancer cells. In the present study we have tested the potential of eleven mono- and dimeric naphthylisoquinoline compounds against two breast cancer cell lines, MCF-7 and MDA-MB-231. Three out of the compounds (agents 1, 4, and 11) showed significant activities against both tested cancer cell lines. Further mechanistic investigations revealed that all of the three substances induce apoptotic cell death via its intrinsic pathway by causing deformation of the nuclear membrane, disruption of the mitochondrial membrane potential (MMP), and elevated reactive oxygen species (ROS) production in both cell lines. Flow cytometric analysis using Annexin V - FITC/PI double staining showed an increased number of apoptotic cells in both, the early and the late phases.
Insights
Naphthylisoquinoline alkaloids show promise as novel breast cancer treatments. Three compounds effectively induced cancer cell death through apoptosis, offering a potential new therapeutic avenue.
Area of Science:
- Natural Products Chemistry
- Oncology
- Pharmacology
Background:
- Breast cancer is a leading cause of cancer mortality worldwide.
- Current therapies for breast cancer have significant limitations, including resistance and toxicity.
- Naphthylisoquinoline alkaloids are natural products with known anti-infective and anti-cancer activities.
Purpose of the Study:
- To evaluate the efficacy of eleven naphthylisoquinoline alkaloids against breast cancer cell lines.
- To investigate the mechanism of action of active compounds in breast cancer cells.
Main Methods:
- Testing eleven mono- and dimeric naphthylisoquinoline compounds against MCF-7 and MDA-MB-231 breast cancer cell lines.
- Mechanistic studies involving assessment of nuclear membrane deformation, mitochondrial membrane potential (MMP) disruption, and reactive oxygen species (ROS) production.
- Flow cytometry using Annexin V - FITC/PI double staining to quantify apoptosis.
Main Results:
- Three naphthylisoquinoline compounds (agents 1, 4, and 11) demonstrated significant activity against both tested breast cancer cell lines.
- These active compounds induced apoptotic cell death via the intrinsic pathway.
- Induction of apoptosis was characterized by nuclear membrane deformation, MMP disruption, and increased ROS production.
Conclusions:
- Naphthylisoquinoline alkaloids represent a promising class of compounds for breast cancer therapy.
- Agents 1, 4, and 11 induce breast cancer cell death through intrinsic apoptosis.
- Further research into these compounds could lead to novel breast cancer treatments with improved efficacy and reduced side effects.
Related Concept Videos
01:31The Intrinsic Apoptotic Pathway
01:17The Extrinsic Apoptotic Pathway