Anticancer effect of dentatin and dentatin-hydroxypropyl-&beta;-cyclodextrin complex on human colon cancer (HT-29) cell line
Authors: Abdullah Rasedee
Mostafa Saddam Ghaji
Mothanna Sadiq Al-Qubaisi
Peter M Waziri
Wafaa Abd Alwahed Alkaby
Ahmad Bustamam Abdul
Yun Hin Taufiq-Yap
Ashwaq Shakir Al-Abboodi
Journal: Drug Design Development and Therapy (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: HPβCD; anti-apoptotic proteins; apoptosis; natural products; pro-apoptotic proteins.
Affiliations: MAKNA-UPM, Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia, Serdang, Malaysia., Basic Science Branch, Faculty of Dentistry, University of Al-Qadisiyah, Al Diwaniyah, Iraq., Department of Veterinary Laboratory Diagnosis, Faculty of Veterinary Medicine, University Putra Malaysia, Serdang, Malaysia., Department of Biomedical Science, Faculty of Medicine and Health Science, University Putra Malaysia, Serdang, Malaysia., Department of Chemistry, Faculty of Science, University Putra Malaysia, Serdang, Malaysia., Department of Biomedical, Faculty of Biotechnology, University of AL-Qadisiyah, Al Diwaniyah, Iraq., Department of Anatomy and Histology, Faculty of Veterinary Medicine, University of Basrah, Basrah, Iraq., Department of Biochemistry, Kaduna State University, Main Campus, Kaduna, Nigeria.

Abstract:  Introduction: Dentatin (DEN) (5-methoxy-2, 2-dimethyl-10-(1, 1-dimethyl-2propenyl) dipyran-2-one), a natural compound present in the roots of Clausena excavata Burm f, possesses pro-apoptotic and antiproliferative effects in various cancer cells. Because of its hydrophobicity, it is believed that its complexation with hydroxy-β-cyclodextrin (HPβCD) will make it a potent inhibitor of cancer cell growth. In the current work, the molecular mechanisms of apoptosis induced by DEN and DEN-HPβCD complex were demonstrated in human colon HT-29 cancer cells. Materials and methods: After the human colon HT-29 cancer cells were treated with DEN and DEN-HPβCD complex, their effects on the expression of apoptotic-regulated gene markers in mitochondria-mediated apoptotic and death receptor pathways were detected by Western blot analysis and reverse transcription polymerase chain reaction. These markers included caspases-9, 3, and 8, cytochrome c, poly (ADP-ribose) polymerase, p53, p21, cyclin A as well as the Bcl-2 family of proteins. Results: At 3, 6, 12, and 24 µg/mL exposure, DEN and DEN-HPβCD complex significantly affected apoptosis in HT-29 cells through the down-regulation of Bcl-2 and cyclin A in turn, and up-regulation of Bax, p53, p21, cytochrome c at both protein and mRNA levels. DEN and DEN-HPβCD complex also decreased cleaved poly (ADP-ribose) polymerase and induced caspases-3, -8, and -9. Conclusion: Results of this study indicate that the apoptotic pathway caused by DEN and DEN-HPβCD complex are mediated by the regulation of caspases and Bcl-2 families in human colon HT-29 cancer cells. The results also suggest that DEN-HPβCD complex may have chemotherapeutic benefits for colon cancer patients. 

Retracted: No

PubPeer comments:
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