Colorectal, Prostate and Pancreas Human Cancers Targeted Bioassay-guided Isolations and Characterization of Chemical Constituents from Tephrosia apollinea.
BACKGROUND
Cancer is characterized by uncontrolled cell division caused by dysregulation of cell proliferation. Therefore, agents that impair cancer cell proliferation could have potential therapeutic value. Higher plants are considered to be a good source of anticancer agents, and several clinically tested chemotherapeutic agents have been isolated from plants or derived from constituents of plant origin.


METHODS
In the present study, a prenylated flavone (isoglabratephrin) was isolated from aerial parts of Tephrosia apollinea using a bioassay-guided technique. Chemical structure of the isolated compound was elucidated using spectroscopic techniques (NMR, IR, and LC-MC), elemental analysis and confirmed by using single crystal X-ray analysis. The antiproliferative effect of isoglabratephrin was tested using three human cancer cell lines (prostate (PC3), pancreatic (PANC-1), and colon (HCT-116) and one normal cell line (human fibroblast).


RESULTS
Isoglabratephrin displayed selective inhibitory activity against proliferation of PC3 and PANC-1 cells with median inhibitory concentration values of 20.4 and 26.6 μg/ml, respectively. Isoglabratephrin demonstrated proapoptotic features, as it induced chromatin dissolution, nuclear condensation, and fragmentation. It also disrupted the mitochondrial membrane potential in the treated cancer cells.


CONCLUSIONS
Isoglabratephrin could be a new lead to treat human prostate (PC3) and pancreatic (PANC-1) malignancies.
EMAN Testing and Research Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Minden, Pulau Penang. Malaysia.
Loiy Elsir A
LEA
Hassan
Community College, PARS Campus, University of Agriculture, Faisalabad. Pakistan.
Muhammad Adnan
MA
Iqbal
EMAN Testing and Research Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Minden, Pulau Penang. Malaysia.
Saad S
SS
Dahham
EMAN Testing and Research Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Minden, Pulau Penang. Malaysia.
Yasser M
YM
Tabana
EMAN Testing and Research Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Minden, Pulau Penang. Malaysia.
Mohamed B Khadeer
MBK
Ahamed
EMAN Testing and Research Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Minden, Pulau Penang. Malaysia.
Amin M S Abdul
AMSA
Majid
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship; D031304:Tephrosia / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; C546075:isoglabratephrin
Isoglabratephrin; X-ray crystallography; anticancer; apoptosis; prenylated flavone