Title:CJK-7, a Novel Flavonoid from Paulownia tomentosa Triggers Cell Death Cascades in HCT-116 Human Colon Carcinoma Cells via Redox Signaling
VOLUME: 18 ISSUE: 3
Author(s):Mahendra Pal Singh, Ki Hun Park, Tejinder Pal Khaket and Sun Chul Kang*
Affiliation:Department of Biotechnology, Collage of Engineering, Daegu University, Gyeongsan, Gyeongbuk, 38453, Division of Applied Science, IALS, Gyeongsan National University, Jinju 660-701, Department of Biotechnology, Collage of Engineering, Daegu University, Gyeongsan, Gyeongbuk, 38453, Department of Biotechnology, Collage of Engineering, Daegu University, Gyeongsan, Gyeongbuk, 38453
Keywords:Apoptosis, autophagy, colon cancer, natural compounds, oxidative stress, redox signaling.
Abstract:Background: Colon cancer is the second most common cancer to cause death worldwide. About half
of colon cancers patients require adjuvant therapy to control relapse following surgical resection. Therefore,
abolition of tumor cell progression using an effective chemotherapeutic agent holds a feasible approach to treat
patients suffering from colon cancer. In the present study, we evaluated the effects of geranylated flavonoid
CJK-7, isolated from Paulownia tomentosa on HCT-116 human colon carcinoma cells.
Materials and Methods: The effects of CJK-7 as an active component on HCT-116 cells programmed cell death
and its underlying molecular mechanism were examined by using MTT assay, morphological assessment,
H2DCFDA staining, Fura-2AM staining, Hoechst-33342 staining, comet assay, Acridine orange staining, mitochondrial
membrane potential (ΔΨm) assay and Western blot analyses.
Results and Conclusion: The results revealed that, CJK-7 was capable of inducing caspase-dependent cell death
events in cancer cells. Moreover, it was involved in up-regulation of autophagy signaling as evidenced by enhanced
expression of LC3I/II. We also noticed stimulated expression of endoplasmic reticulum stress markers
and phosphorylation of c-Jun NH2-terminal kinase (JNK), which was associated with up-regulated expression of
p53, PUMA, Atg5 and Beclin-1, and down-regulation of Bcl-2, stressing the interaction of ROS on the aforementioned
signaling. Furthermore, exposure to ROS scavengers (N-acetyl-l-cysteine (NAC), and JNK-specific
inhibitor SP600125) significantly reversed the effects of CJK-7 by down-regulating apoptosis and autophagy
signatures in HCT-116 cancer cells. Collectively our findings clarify the ROS-dependent regulatory effect of
CJK-7 on programmed cell death signaling events in HCT-116 cancer cells while depicting its virile pro-oxidant
capacity.
