Shaik Othuman, Faiqah Husna
(2016)
Investigation Of The Anti-Proliferative Effect Of Synthetic 1-[(Bromomethyl)(Phenyl) Methyl]-2-(2,4-Dinitrophenyl)Hydrazine Derivative On Cervical Cancer Cells.
Masters thesis, Universiti Sains Malaysia.
Abstract
Kanser pangkal rahim masih kekal sebagai kanser yang kedua tertinggi di
kalangan wanita dan punca ketiga utama kematian walaupun pelbagai rawatan sedia ada.
Kurang keberkesanan rawatan tersebut telah menyebabkan para saintis mencari rawatan
alternatif bagi penyakit ini. Strategi agen anti-proliferatif baru untuk kanser pangkal
rahim adalah salah satu inovasi yang penting dalam melawan penyakit yang sengsara ini.
Walaupun derivatif hydrazone sintetik telah digunakan secara meluas dalam
penyelidikan kanser tetapi mekanisme anti-kanser yang sebenarnya yang ditunjukkan
oleh bahan kimia ini masih belum diketahui. Kajian ini cuba menjelaskan kesan-kesan
anti-proliferatif1 - [( Bromomethyl ) ( phenyl ) methyl ] -2- (2,4- dinitrophenyl ) hidrazin
(C14H11BrN4O4) derivatif (kompaun Hydrazone) pada sel-sel kanser pangkal rahim
melalui penentuan kepekatan perencatan (IC50), assay anti- proliferatif, assay apoptosis,
assay kitaran sel, analisis Western Blot, assay invasi dan analisis cytotoxicity .Hasil
kajian menunjukkan dos IC50 bagi kompaun Hydrazone adalah 0.03mg/ml pada sel-sel
kanser pangkal rahim dan berjaya menghalang proliferasi sel-sel kanser berbanding
dengan sel-sel kanser yang tidak dirawat. Di samping itu, aliran sitometri analisis
mengesahkan hydrazone derivatif menyebabkan pembantutan sintesis deoxyribonucleic
acid (DNA) pada fasa S dan G2 / M tanpa induksi apoptosis. Analisa ‘ western blot’
menunjukkan peningkatan ekspresi protein p27kip1 dan PCNA serta merencatkan
ekspresi protein Cyclin E2 dan cdc25. Kesan anti-metastasis dikaji melalui analisis
invasi dan ia menunjukkan kompaun hydrazone telah menghalang 50.94 % invasi sel
HeLa. Kesimpulannya kompaun hydrazone memiliki kesan anti-proliferatif pada sel
HeLa.
Cervical cancer remains as the second most common type of cancer in women and it
is the third leading cause of death despite various treatments that are available.
Inefficiency of present treatments had triggered scientists to seek for an alternative
treatment for this disease. Development of new anti-proliferative agent for cervical
cancer is an important innovation in fighting this miserable disease. Although, synthetic
hydrazone derivatives are widely being used in cancer research, the actual anticancer
mechanism shown by these chemicals is still not yet understood. Therefore this study
aimed to elucidate the anti-proliferative effects of the 1-[(Bromomethyl)(phenyl)methyl]
-2-(2,4 -dinitrophenyl) hydrazine (C14H11BrN4O4) derivative (Hydrazone compound) on
cervical cancer cells through determination of inhibitory concentration (IC50),
anti-proliferative assay, apoptosis assay, cell cycle assay, western blot analysis, invasion
assay and cytotoxicity analysis. The results showed the IC50 of the hydrazone compound
at 0.03mg/ml on the cervical cancer cells and inhibits the proliferation of cervical cancer
cells in a dose and time-dependent manner compared to the untreated control. In addition,
the flow cytometry analysis confirmed the hydrazone derivative causes S and G2/M
phase cell cycle arrest without induction of apoptosis. Western blot analysis showed that
hydrazone compound had increased the p27kip1 and PCNA and suppressed Cyclin E2 and
cdc25 protein expression. The anti-metastatic effect was studied through invasion assay
and it showed the hydrazone compound had inhibited 50.94% of HeLa cells invasion. It is concluded the hydrazone compound possesses anti-proliferative effect on HeLa cells.
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