CJK-7, a novel flavonoid from Paulownia tomentosa, triggers cell death cascades in HCT-116 human colon carcinoma cells via redox signaling.

CJK-7, a novel flavonoid from Paulownia tomentosa, triggers cell death cascades in HCT-116 human colon carcinoma cells via redox signaling.

Anticancer Agents Med Chem. 2017 Oct 26;:

Authors: Singh MP, Park KH, Kang SC

Abstract
BACKGROUND: Colon cancer is the second most common cancer to cause death worldwide. About half of colon cancer 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.
MATERIAL 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 (∆Ψm) 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.

PMID: 29076434 [PubMed - as supplied by publisher]

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