Clausenidin induces caspase-dependent apoptosis in colon cancer.

Autor: Waziri PM; MAKNA Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia. petermwaziri@gmail.com.; Department of Biochemistry, Kaduna State University, Main Campus, PMB 2336, Kaduna, Nigeria. petermwaziri@gmail.com., Abdullah R; Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, University Putra Malaysia, Serdang, Selangor, Malaysia., Yeap SK; Laboratory of Vaccine and Therapeutics, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia., Omar AR; Laboratory of Vaccine and Therapeutics, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia., Kassim NK; Department of Chemistry, Faculty of Science, University Putra Malaysia, Serdang, Selangor, Malaysia., Malami I; MAKNA Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia., How CW; Laboratory of Vaccine and Therapeutics, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia., Etti IC; MAKNA Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia., Abu ML; Enzyme Technology Research Laboratory, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia.
Jazyk: angličtina
Zdroj: BMC complementary and alternative medicine [BMC Complement Altern Med] 2016 Jul 29; Vol. 16, pp. 256. Date of Electronic Publication: 2016 Jul 29.
DOI: 10.1186/s12906-016-1247-1
Abstrakt: Background: Clausena excavata Burm.f. is a shrub traditionally used to treat cancer patients in Asia. The main bioactive chemical components of the plant are alkaloids and coumarins. In this study, we isolated clausenidin from the roots of C. excavata to determine its apoptotic effect on the colon cancer (HT-29) cell line.
Method: We examined the effect of clausenidin on cell viability, ROS generation, DNA fragmentation, mitochondrial membrane potential in HT-29 cells. Ultrastructural analysis was conducted for morphological evidence of apoptosis in the treated HT-29 cells. In addition, we also evaluated the effect of clausenidin treatment on the expression of caspase 3 and 9 genes and proteins in HT-29 cells.
Result: Clausenidin induced a G0/G1 cell cycle arrest in HT-29 cells with significant (p < 0.05) dose-dependent increase in apoptotic cell population. The DNA fragmentation assay also showed apoptotic features in the clausenidin-treated HT-29 cells. Clausenidin treatment had caused significant (p < 0.05) increases in the expression of caspase 9 protein and gene in HT-29 cells and mitochondrial ROS and mitochondrial membrane depolarization. The results suggest the involvement of the mitochondria in the caspase-dependent apoptosis in clausenidin-treated colon cancer cells.
Conclusion: Clausenidin induces a caspase-dependent apoptosis in colon cancers through the stimulation of the mitochondria. The study demonstrates the potential of clausenidin for use in the treatment of colon cancers.
Databáze: MEDLINE
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