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The Growth Suppressing Effects of Girinimbine on Hepg2 Involve Induction of Apoptosis and Cell Cycle Arrest
UPM-Makna Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
Centre for Natural Products and Drug Discovery (CENAR), Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
* Author to whom correspondence should be addressed.
Received: 18 May 2011; in revised form: 6 July 2011 / Accepted: 3 August 2011 / Published: 23 August 2011
(This article belongs to the Special Issue Alkaloids
Abstract: Murraya koenigii is an edible herb widely used in folk medicine. Here we report that girinimbine, a carbazole alkaloid isolated from this plant, inhibited the growth and induced apoptosis in human hepatocellular carcinoma, HepG2 cells. The MTT and LDH assay results showed that girinimbine decreased cell viability and increased cytotoxicity in a dose-and time-dependent manner selectively. Girinimbine-treated HepG2 cells showed typical morphological features of apoptosis, as observed from normal inverted microscopy and Hoechst 33342 assay. Furthermore, girinimbine treatment resulted in DNA fragmentation and elevated levels of caspase-3 in HepG2 cells. Girinimbine treatment also displayed a time-dependent accumulation of the Sub-G0/G1 peak (hypodiploid) and caused G0/G1-phase arrest. Together, these results demonstrated for the first time that girinimbine could effectively induce programmed cell death in HepG2 cells and suggests the importance of conducting further investigations in preclinical human hepatocellular carcinoma models, especially on in vivo efficacy, to promote girinimbine for use as an anticancer agent against hepatocellular carcinoma.
Keywords: anticancer; apoptosis; carbazole alkaloid; cell cycle arrest; girinimbine; pyranocarbazole
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MDPI and ACS Style
Syam, S.; Abdul, A.B.; Sukari, M.A.; Mohan, S.; Abdelwahab, S.I.; Wah, T.S. The Growth Suppressing Effects of Girinimbine on Hepg2 Involve Induction of Apoptosis and Cell Cycle Arrest. Molecules 2011, 16, 7155-7170.
Syam S, Abdul AB, Sukari MA, Mohan S, Abdelwahab SI, Wah TS. The Growth Suppressing Effects of Girinimbine on Hepg2 Involve Induction of Apoptosis and Cell Cycle Arrest. Molecules. 2011; 16(8):7155-7170.
Syam, Suvitha; Abdul, Ahmad Bustamam; Sukari, Mohd. Aspollah; Mohan, Syam; Abdelwahab, Siddig Ibrahim; Wah, Tang Sook. 2011. "The Growth Suppressing Effects of Girinimbine on Hepg2 Involve Induction of Apoptosis and Cell Cycle Arrest." Molecules 16, no. 8: 7155-7170.