Harmalol

DNA binding and apoptotic induction ability of harmalol in HepG2: Biophysical and biochemical approaches.[Pubmed:27590872]

Chem Biol Interact. 2016 Oct 25;258:142-52.

Harmalol administration caused remarkable reduction in proliferation of HepG2 cells with GI50 of 14.2 muM, without showing much cytotoxicity in embryonic liver cell line, WRL-68. Data from circular dichroism (CD) and differential scanning calorimetric (DSC) analysis of Harmalol-CT DNA complex shows conformational changes with prominent CD perturbation and stabilization of CT DNA by 8 degrees C. Binding constant and stoichiometry was calculated using the above biophysical techniques. The Scatchard plot constructed from CD data showed cooperative binding, from which the cooperative binding affinity (K'omega) of 4.65 +/- 0.7 x 10(5) M(-1), and n value of 4.16 were deduced. The binding parameter obtained from DSC melting data was in good agreement with the above CD data. Furthermore, dose dependent apoptotic induction ability of Harmalol was studied in HepG2 cells using different biochemical assays. Generation of ROS, DNA damage, changes in cellular external and ultramorphology, alteration of membrane, formation of comet tail, decreased mitochondrial membrane potential and a significant increase in Sub Go/G1 population made the cancer cell, HepG2, prone to apoptosis. Up regulation of p53 and caspase 3 further indicated the apoptotic role of Harmalol.

Therapeutic Role of Harmalol Targeting Nucleic Acids: Biophysical Perspective and in vitro Cytotoxicity.[Pubmed:29231137]

Mini Rev Med Chem. 2018;18(19):1624-1639.

BACKGROUND: Harmalol, a beta carboline alkaloid, shows remarkable importance in the contemporary biomedical research and drug discovery programs. With time, there is emerging interest in search for better anti-cancer drugs of plant origin with high activity and lower toxicity. Most of the chemotherapeutic agents due to their non-specific target and toxicity on active healthy cells, use is often restricted, necessitating search for newer drugs having greater potentiality. OBJECTIVE: The review highlighted the interaction of Harmalol with nucleic acids of different motifs as sole target biomolecules and in vitro cytotoxicity of the alkaloid in human cancer cell lines with special emphasis on its apoptotic induction ability. METHODS: Binding study and in vitro cytotoxicity was performed using several biophysical techniques and biochemical assays, respectively. RESULTS: Data from competition dialysis, UV and fluorescence spectroscopic analysis, circular dichroism, viscometry and isothermal calorimetry shows binding and interaction of Harmalol with several natural and synthetic nucleic acids, both DNA and RNA, of different motifs. Furthermore, apoptotic hallmarks like internucleosomal DNA fragmentation, membrane blebbing, cell shrinkage, chromatin condensation, change of mitochondrial membrane potential, comet tail formation and ROS (reactive oxygen species) dependent cytotoxicity being analyzed in the Harmalol treated cancer cells. CONCLUSION: These results stating the therapeutic role of Harmalol, will lead to the interesting knowledge on the cytotoxicity, mode, mechanism, specificity of binding and correlation between structural aspects and energetics enabling a complete set of guidelines for design of new drugs.