Suppression of HeLa cancer cell proliferation in-vitro through sonoporation

Abstract

Whilst being tipped as a possible drug delivery mechanism, sonoporation has recently drawn interest over its direct role in suppressing the growth of several cancerous cells. To examine this phenomenon, we have investigated whether sonoporation can hinder the proliferation of the HeLa cervical cancer cell line that is known to multiply at an abnormally fast pace. The deoxyribonucleic acid (DNA) synthesis duration (Ts) of HeLa cells was determined using bivariate bromodeoxyuridine (BrdUrd)/DNA flow cytometry. HeLa cells in the synthesizing phase (S-phase) of the cell cycle were first labeled with BrdUrd (10uM) for 20 min. Subsequently, 3% v/v microbubbles were added to the cell suspension, and pulsed ultrasound was applied for 1 min to trigger sonoporation (1MHz frequency, 10% duty cycle, 1kHz pulse repetition frequency, 0.3MPa peak negative pressure). Ts was determined by analyzing the relative movement of the BrdUrd-labeled cells through the cell cycle at three post-sonoporation time points (0, 3, 6hrs), by using fluorescein isothiocyanate and propidium iodide that respectively stained BrdUrd and DNA. Results show that the Ts for the treated cells was increased to 15.5hrs as compared to 8.6hrs for the untreated ones. We conclude that sonoporation suppressed HeLa cells' proliferation through lengthening their DNA synthesis.