Dentatin from Clausena excavata Induces Apoptosis in HepG2 Cells via Mitochondrial Mediated Signaling

Andas, A Reenaa Joys; Abdul, Ahmad Bustamam; Rahman, Heshu Sulaiman; Sukari, Mohd Aspollah; Abdelwahab, Siddig Ibrahim; Samad, Nozlena Abdul; Anasamy, Theebaa; Arbab, Ismail Adam

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저자정보: Andas, A Reenaa Joys (UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia) Abdul, Ahmad Bustamam (UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia) Rahman, Heshu Sulaiman (UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia) Sukari, Mohd Aspollah (Department of Chemistry, Faculty of Science, Universiti Putra Malaysia) Abdelwahab, Siddig Ibrahim (Medical Research Center, Faculty of Medicine, Jazan University) Samad, Nozlena Abdul (UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia) Anasamy, Theebaa (UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia) Arbab, Ismail Adam (UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제16권 제10호

발행연도: 2015.1

수록면: 4,311 - 4,316 (6page)

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Hepatocellular carcinoma (HCC) is a primary liver cancer with high global incidence and mortality rates. Current candidate drugs to treat HCC remain lacking and those in use possess undesirable side effects. In this investigation, the antiproliferative effects of dentatin (DTN), a natural coumarin, were evaluated on HepG2 cells and DTN's probable preliminary molecular mechanisms in apoptosis induction were further investigated. DTN significantly (p<0.05) suppressed proliferation of HepG2 cells with an $IC_{50}$ value of $12.0{\mu}g/mL$, without affecting human normal liver cells, WRL-68 ($IC_{50}$ > $50{\mu}g/mL$) causing $G_0/G_1$ cell cycle arrest via apoptosis induction. Caspase colorimetric assays showed markedly increased levels of caspase-3 and caspase-9 activities throughout the treatment period. Western blotting of treated HepG2 cells revealed inhibition of $NF-{\kappa}B$ that triggers the mitochondrial-mediated apoptotic signaling pathway by up-regulating cytoplasmic cytochrome c and Bax, and down-regulating Bcl-2 and Bcl-xL. The current findings suggest DTN has the potential to be developed further as an anticancer compound targeting human HCC.

#Dentatin #HepG2 #apoptosis #mitochondrial-mediated signaling pathway

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