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Posted at Nov 8, 2010 by JG
IADS Lecture of the Month – Oktober- by Karen Voon Kai Rou, Malaysia
Share on Facebook | Share on zahnigroups | Share on ALUMNIGROUPSHYDRAZONE DERIVATIVE DEMONSTRATED PROMISING CHEMOPREVENTIVE ACTIVITY VIA ITS INHIBITORY EFFECT AND APOPTOSIS INDUCTION ON HUMAN TONGUE CARCINOMA CELLS
IADS Lecture of the Month
Article written by: Karen Voon Kai Rou (Universiti Sains Malaysia)
Oral cancer is the eleventh most common cancer worldwide and in south-central Asia, it ranks among the three most common types of cancer. Over 90 percent of all oral malignancies are squamous cell carcinoma, which arise from the oral mucosal lining. Oral cancer causes considerable morbidity and is associated with a five-year survival rate of less than 50 percent. Furthermore, the survival rate for oral cancer has remained essentially unchanged over the past few decades. These alarming statistics on oral cancer have led to our interest in investigating the effectiveness of this newly synthesized Hydrazone derivative, 1-[(Bromomethyl)(phenyl)methyl]-2-(2,4-dinitrophenyl)hydrazine in oral cancer chemoprevention by using tongue carcinoma cells as in vitro model.
Karen Voon Kai Rou
Cancer chemoprevention is the use of natural, synthetic, or biologic chemical agents to reverse, suppress, or prevent carcinogenic progression to invasive cancer. The success of several recent clinical trials in preventing cancer in high-risk populations suggests that chemoprevention is a rational and appealing strategy. The chemical used in this study belongs to the class of compounds known as the Hydrazones. This is an important class of compounds for new drug development and some of the Hydrazone derivatives have shown to exhibit anti-cancer properties.
Figure 1. Anti-proliferative effect of the Hydrazone derivative until eight days of treatment
The study showed that the compound inhibited the growth of tongue carcinoma cells with an inhibitory concentration (IC50) of 0.01 mg/ml in dose and time-dependent manner. Consequently, the compound induced a two-fold increase in apoptotic activity and a G0G1 phase cell cycle arrest compared to untreated cells. Exposure of the cells to the compound also resulted in alterations of cell morphology including vacuolization and cellular shrinkage. On live-death analysis under confocal microscope using Calcein and Ethidium stain, it was confirmed that the compound exerted cell death. Further study demonstrated that the compound has no cytotoxic effect on normal mouse skin fibroblast cells.
Figure 2. Two-fold increase of apoptotic activity in the early and late apoptosis stages in treated cells
These findings suggested that the Hydrazone derivative showed its potentiality as chemopreventive agent, which could be attributed, in part, to its proliferation inhibition, apoptosis induction and cell cycle arrest of tongue carcinoma cells. Continuing research of the potentiality of the Hydrazone derivative as chemopreventive agent offers hope that, in the future, even more people with this disease will be treated successfully and people with oral cancer can look forward to a better quality of life.
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