ผลของ 4F-phenyl pyrazole ในการเหนี่ยวนำการตายแบบอะพอพโทซิส ในเซลล์มะเร็งลำไส้ใหญ่และทวารหนัก T84

Podchanart Wanitchakool; Lalida  Sirianant; Nutnaree  Srisarakorn; Premyuda  Hempoom; Pakit Kumboonma

Authors

Podchanart Wanitchakool Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Nakhon Pathom Province, Thailand
Lalida Sirianant Department of Applied Biology, Faculty of Science and Liberal Arts, Rajamangala University of Technology Isan, Nakhon Ratchasima Province, Thailand
Nutnaree Srisarakorn Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Nakhon Pathom Province, Thailand
Premyuda Hempoom Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Nakhon Pathom Province, Thailand
Pakit Kumboonma Department of Applied Chemistry, Faculty of Science and Liberal Arts, Rajamangala University of Technology Isan, Nakhon Ratchasima Province, Thailand

Keywords:

4F-phenyl pyrazole, [6]-shogaol, Colorectal cancer, Apoptosis

Abstract

Colorectal cancer is the second most common cancer globally and the third leading cause of cancer death. A delayed diagnosis and high cost of treatment contribute to high mortality. Thai herbs have gained more interest as chemopreventive agents. Ginger is one of the most widely studied herbs composing of many bioactive compounds for treating diseases, including [6]-shogaol. Previous studies have reported that [6]-shogaol exhibited antiproliferative activity against various human cancer cells. However, its therapeutic effects were limited due to physicochemical properties. Therefore, the present study aimed to investigate the antiproliferative activity of [6]-shogaol derivatives including PK4F1, PK2ME and PK4NO2, on human colorectal (T84) cancer cells. Morphological analysis of T84 cells under a microscope revealed that PK4F1, or 4F-phenyl pyrazole, exhibited strong antiproliferative effects compared to PK2ME and PK4NO2. The morphological changes observed were comparable to those induced by [6]-shogaol. In addition, PK4F1 possessed a tremendous effect on inhibiting colony formation. Cells viability assays showed a reduction in T84 cells viability with an IC₅₀ of 16.76 µM. Flow cytometry assay showed that treatment with 20 µM of PK4F1 significantly increased apoptotic cell death. Moreover, fluorescence microscopy revealed that PK4F1 could induce phosphatidyl serine exposure chromatin condensation and DNA fragmentation, a hallmark of apoptosis. These findings suggested that PK4F1 inhibited the growth of T84 cells in dose-dependent manner by inducing apoptosis. Therefore, PK4F1 might be a promising candidate for further development as an anti-colorectal cancer agent. Additional studies are required to elucidate its underlying mechanisms.

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