Sinensetin isolated from Orthosiphon aristatus inhibits cell proliferation and induces apoptosis in hepatocellular carcinoma cells

• Published in: Process biochemistry (1991) 2020-01, Vol.88, p.213-221
• Main Authors: Samidurai, Divakar, Pandurangan, Ashok Kumar, Krishnamoorthi, Senthil Kumar, Perumal, Madan Kumar, Nanjian, Raaman
• Format: Article
• Language: English
• Subjects: Anticancer properties; Antioxidants; Antitumor activity; Apoptosis; Bcl-x protein; Cell cycle; Cell cycle analysis; Cell proliferation; Cytotoxicity; DNA fragmentation; Flow cytometry; G1 phase; Hepatocellular carcinoma; HepG2 cells; Ionization; Liver cancer; Mass spectrometry; Mass spectroscopy; NMR; Nuclear magnetic resonance; Organic chemistry; Orthosiphon aristatus; Physical characteristics; PTEN protein; Sinensetin; Suppressors
• ISSN: 1359-5113; 1873-3298
• DOI: 10.1016/j.procbio.2019.09.031

[Display omitted] •Sinensetin, an active compound derived from Orthosiphon aristatus leaves.•Sinensetin exhibits antiproliferative effects in HepG2 cells and induces apoptosis.•Molecular evident of apoptotic activation were confirmed by mRNA and protein level. Orthosiphon aristatus is a traditional folk medicine extensively used in Southeast Asia because of its various pharmacological effects, including antioxidant, antitumor, and hypoglycemic activities. Orthosiphon extracts have been found to be cytotoxic to hepatocellular carcinoma (HCC) cells, which is attributed to their phytochemical content. However, the mechanism of action underlying the cytotoxic effects remains unclear. Hence, the present study investigated the effect of Sinensetin purified from O. aristatus on HCC in vitro. Sinensetin was isolated from O. aristatus leaves and the chemical structure was confirmed by ultra violet (UV)-vis, infrared (IR), nuclear magnetic resonance (NMR), and electrospray ionization mass spectrometry (ESI-MS). The results revealed that 24-h treatment with the purified compound markedly inhibited the survival of HepG2 cells, with IC50 of 39.93 ± 1.10 μg/mL. HepG2 cells treated with the IC50 of Sinensetin showed characteristic morphological changes, as determined by PI and AO/Etbr dual staining, including DNA fragmentation, thus confirming the apoptosis induction. Sinensetin induced cell cycle arrest at G0/G1 phase, and the data were substantiated by flow cytometry. Furthermore, Sinensetin modulated key signaling molecules; anti-apoptotic Bcl-xL was down-regulated, whereas the expressions of tumor suppressors TRAIL and PTEN were up-regulated. We conclude that Sinensetin can be effective against HCC.