Antiproliferative Effect and Mediation of Apoptosis in Human Hepatoma HepG2 Cells Induced by Djulis Husk and Its Bioactive Compounds.

Dom-Gene Tu,Heuy-Ling Chu,Charng-Cherng Chyau,Shu-Chen Wang,Pin-Der Duh,Shih-Ying Chen

doi:10.3390/foods9101514

Abstract

The antiproliferative effect and mediation of apoptosis in human hepatoma HepG2 cells induced by djulis husk and its bioactive compounds was investigated. The ethanolic extracts of djulis husk (EEDH) at 50, 250, and 500 µg/mL induced remarkable cytotoxicity on HepG2 cells. By flow cytometry analysis, EEDH slowed down the cell cycle at the Sub-G0 phase after 24 h of incubation. Moreover, all EEDH treatment induced an apoptotic response in HepG2 cells. EEDH-induced apoptosis was associated with the attenuation of mitochondrial transmembrane potentials (ΔΨm), an increase in Bax/Bcl-2 ratio, activation of caspase-3, and poly(ADP-ribose)polymerase (PARP) cleavage, as well as an increase in reactive oxygen species (ROS) generation. According to the HPLC-DAD and HPLC-MS/MS analysis, quercetin and kaempferol derivatives and another sixteen compounds were present in EEDH. Quercetin and kaempferol at 25–150 μM showed antiproliferative action and induced apoptosis on HepG2 cells, which may in part account for the anticancer activity of EEDH. Overall, EEDH may be a potent chemopreventive agent due to apoptosis in HepG2 cells.

Highlights

A World Health Organization (WHO) survey indicated that cancer is the second leading cause of death globally and accounted for an estimated 9.6 million deaths in 2018
lactate dehydrogenase (LDH) is released from the cells when cells are damaged
The LDH leakage may be regarded as an indicator of cytotoxicity in apoptosis research

Summary

Introduction

A World Health Organization (WHO) survey indicated that cancer is the second leading cause of death globally and accounted for an estimated 9.6 million deaths in 2018. Liver cancer is one of the five most common causes of cancer death with 782,000 deaths [1]. Chemotherapy, radiotherapy, and liver transplantation are the treatment options available for treating liver cancer [2]; no perfect treatment has been developed far. An alternative therapy for treating liver cancer is urgently needed. Epidemiological evidence and several studies show that a diet that is rich in natural bioactive compounds is associated with lower risk of human diseases [3]. Many studies have strived to search for natural chemopreventive agents to reduce the mortality caused by liver cancer

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