Abstract
The present study relates to the induction of apoptosis thereof cytotoxicity and anti-cancer activity displayed by semi-synthetic analog of Boswellic acid i.e. 3-α-Butyryloxy-β-boswellic acid (BOBA). The cytotoxicity data revealed the differential sensitivity of cancer cell lines towards BOBA which may display its impact against different types of cancers. Considering the inhibitory potential of BOBA, we further sought to understand the target for BOBA deciphering the mechanism of action leading to apoptotic cell death and it was for the first time reported about the triterpenoid ring especially the β-boswellic acid derivative is targeting PI3K pathway. Our data revealed that BOBA treatment provides evidence about the apoptotic nature showing the potential of targeting mitochondria dependent pathways during apoptosis in HL-60 cells. BOBA induced hypo-diploid sub-G1 DNA population in HL-60 cells as was also evident from the pattern of DNA fragmentation and mitochondrial membrane potential (ΛΨm) loss. Morphological analysis under fluorescent and scanning electron microscopy displayed typical features such as cell shrinkage, membrane blebbing, chromatin condensation and nuclear fragmentation. These events paralleled with the down-regulation of NF-κB and induced PARP cleavage. Furthermore, it is noteworthy that BOBA also depicted significant growth inhibition in Ehrlich Ascitic Tumour (EAT), Ehrlich Ascitic Carcinoma (EAC) and Sarcoma- 180 tumour models. Taken together, BOBA treatment may represent as potential agent to the currently available anticancer agents in both prophylactic and/or therapeutic applications. Also, our findings may open up a new perspective in the construction of novel anticancer agents based on boswellic acids that will facilitate the development of these agents for anticancer therapeutics.
Keywords: DNA repair, Apoptosis, Cancer, Natural Products, Drug, Signaling, PI3K, Boswellia serrata.
Anti-Cancer Agents in Medicinal Chemistry
Title:NF-κB Down–regulation and PARP Cleavage by novel 3-α-butyryloxy-β-boswellic Acid Results in Cancer Cell Specific Apoptosis and in vivo Tumor Regression
Volume: 13 Issue: 5
Author(s): Yasrib Qurishi, Abid Hamid, Parduman R. Sharma, Zahoor A. Wani, Dilip M. Mondhe, Shashank K. Singh, Mohmmad A. Zargar, Samar S. Andotra, Bhahwal A. Shah, Subhash C. Taneja and Ajit K. Saxena
Affiliation:
Keywords: DNA repair, Apoptosis, Cancer, Natural Products, Drug, Signaling, PI3K, Boswellia serrata.
Abstract: The present study relates to the induction of apoptosis thereof cytotoxicity and anti-cancer activity displayed by semi-synthetic analog of Boswellic acid i.e. 3-α-Butyryloxy-β-boswellic acid (BOBA). The cytotoxicity data revealed the differential sensitivity of cancer cell lines towards BOBA which may display its impact against different types of cancers. Considering the inhibitory potential of BOBA, we further sought to understand the target for BOBA deciphering the mechanism of action leading to apoptotic cell death and it was for the first time reported about the triterpenoid ring especially the β-boswellic acid derivative is targeting PI3K pathway. Our data revealed that BOBA treatment provides evidence about the apoptotic nature showing the potential of targeting mitochondria dependent pathways during apoptosis in HL-60 cells. BOBA induced hypo-diploid sub-G1 DNA population in HL-60 cells as was also evident from the pattern of DNA fragmentation and mitochondrial membrane potential (ΛΨm) loss. Morphological analysis under fluorescent and scanning electron microscopy displayed typical features such as cell shrinkage, membrane blebbing, chromatin condensation and nuclear fragmentation. These events paralleled with the down-regulation of NF-κB and induced PARP cleavage. Furthermore, it is noteworthy that BOBA also depicted significant growth inhibition in Ehrlich Ascitic Tumour (EAT), Ehrlich Ascitic Carcinoma (EAC) and Sarcoma- 180 tumour models. Taken together, BOBA treatment may represent as potential agent to the currently available anticancer agents in both prophylactic and/or therapeutic applications. Also, our findings may open up a new perspective in the construction of novel anticancer agents based on boswellic acids that will facilitate the development of these agents for anticancer therapeutics.
Export Options
About this article
Cite this article as:
Qurishi Yasrib, Hamid Abid, Sharma Parduman R., Wani Zahoor A., Mondhe Dilip M., Singh Shashank K., Zargar Mohmmad A., Andotra Samar S., Shah Bhahwal A., Taneja Subhash C. and Saxena Ajit K., NF-κB Down–regulation and PARP Cleavage by novel 3-α-butyryloxy-β-boswellic Acid Results in Cancer Cell Specific Apoptosis and in vivo Tumor Regression, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (5) . https://dx.doi.org/10.2174/1871520611313050012
DOI https://dx.doi.org/10.2174/1871520611313050012 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Insight into p95HER2 in Breast Cancer: Molecular Mechanisms and Targeted Therapies
Recent Patents on DNA & Gene Sequences The Biological Role of mTOR in the Pathogenesis of Solid Tumors: An Overview
Current Enzyme Inhibition Genitourinary Tract Tumors in Children: An Update
Current Pediatric Reviews Current Strategies for Probing Substrate Specificity of Proteases
Current Medicinal Chemistry Hybrid Organic-Inorganic Scaffolding Biomaterials for Regenerative Therapies
Current Organic Chemistry Real-Time PCR: Revolutionizing Detection and Expression Analysis of Genes
Current Genomics Preferentially Expressed Antigen in Melanoma (PRAME) and the PRAME Family of Leucine-Rich Repeat Proteins
Current Cancer Drug Targets Shared Signaling Pathways Between Endocrine and Immune System Receptors: The Model of Gamma Chain
Current Signal Transduction Therapy The Biology of Neurotrophins, Signalling Pathways, and Functional Peptide Mimetics of Neurotrophins and their Receptors
CNS & Neurological Disorders - Drug Targets Efficacy and Toxicological Studies of Cremophor EL Free Alternative Paclitaxel Formulation
Current Drug Safety Using Natural Compounds to Target KRAS Mutated Non-Small Cell Lung Cancer
Current Medicinal Chemistry Chemical Advances in Therapeutic Application of Exosomes and Liposomes
Current Medicinal Chemistry Biosafety of Gene Therapy Vectors Derived From Herpes Simplex Virus Type 1
Current Gene Therapy Current Understanding of HSP90 as a Novel Therapeutic Target: An Emerging Approach for the Treatment of Cancer
Current Pharmaceutical Design Regulation of T cell Apoptosis during the Immune Response
Current Molecular Medicine Lung Cancer Chemotherapy, New Treatment and Related Patents
Recent Patents on Anti-Cancer Drug Discovery NFAT Gene Family in Inflammation and Cancer
Current Molecular Medicine Between Bench and Bed Side: PI3K Inhibitors
Current Molecular Pharmacology Marine Natural Products and Related Compounds as Anticancer Agents: an Overview of their Clinical Status
Anti-Cancer Agents in Medicinal Chemistry Current Perspective of Natural Alkaloid Carbazole and its Derivatives as Antitumor Agents
Anti-Cancer Agents in Medicinal Chemistry