title: Pulchrin A, a New Natural Coumarin Derivative of Enicosanthellum pulchrum, Induces Apoptosis in Ovarian Cancer Cells via Intrinsic Pathway.
abstract: Drug resistance presents a challenge in chemotherapy and has attracted research interest worldwide and particular attention has been given to natural compounds to overcome this difficulty. Pulchrin A, a new compound isolated from natural products has demonstrated novel potential for development as a drug. The identification of pulchrin A was conducted using several spectroscopic techniques such as nuclear magnetic resonance, liquid chromatography mass spectrometer, infrared and ultraviolet spectrometry. The cytotoxicity effects on CAOV-3 cells indicates that pulchrin A is more active than cisplatin, which has an IC50 of 22.3 μM. Significant changes in cell morphology were present, such as cell membrane blebbing and formation of apoptotic bodies. The involvement of phosphatidylserine (PS) in apoptosis was confirmed by Annexin V-FITC after a 24 h treatment. Apoptosis was activated through the intrinsic pathway by activation of procaspases 3 and 9 as well as cleaved caspases 3 and 9 and ended at the executioner pathway, with the occurrence of DNA laddering. Apoptosis was further confirmed via gene and protein expression levels, in which Bcl-2 protein was down-regulated and Bax protein was up-regulated. Furthermore, the CAOV-3 cell cycle was disrupted at the G0/G1 phase, leading to apoptosis. Molecular modeling of Bcl-2 proteins demonstrated a high- binding affinity, which inhibited the function of Bcl-2 proteins and led to cell death. Results of the current study can shed light on the development of new therapeutic agents, particularly, human ovarian cancer treatments.
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Noraziah
authors.initials: N
authors.lastname: Nordin
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Mehran
authors.initials: M
authors.lastname: Fadaeinasab
authors.affiliation: Medical Research Center, Jazan University, Jazan, Kingdom of Saudi Arabia.
authors.forename: Syam
authors.initials: S
authors.lastname: Mohan
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Najihah
authors.initials: N
authors.lastname: Mohd Hashim
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Rozana
authors.initials: R
authors.lastname: Othman
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Hamed
authors.initials: H
authors.lastname: Karimian
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Venus
authors.initials: V
authors.lastname: Iman
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Noorlela
authors.initials: N
authors.lastname: Ramli
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Hapipah
authors.initials: H
authors.lastname: Mohd Ali
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Nazia
authors.initials: N
authors.lastname: Abdul Majid
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001688:Biological Products / Q000737:chemistry* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002853:Chromatography, Liquid; D002945:Cisplatin / Q000494:pharmacology; D003374:Coumarins / Q000737:chemistry*; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010051:Ovarian Neoplasms / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D003374:Coumarins; D010718:Phosphatidylserines; D019253:Proto-Oncogene Proteins c-bcl-2; C030123:coumarin; D002945:Cisplatin