Cell death in HeLa cells upon imperatorin and cisplatin treatment Cell death in HeLa cells upon imperatorin and cisplatin treatment

Abstract

There is growing evidence that commonly applied chemotherapy regimens can be improved by introducing<br />new, specific, active and low side-effect drugs, or by combining substances to obtain the required clinical<br />effect. The aim of the present study was to investigate the effects of imperatorin and cisplatin, applied separately<br />or in combination, on apoptosis, necrosis and autophagy induction in the human cervical carcinoma cell line<br />(HeLa). Imperatorin appeared to be a potent autophagy inducer, rather than a necrotic or apoptotic one. In<br />contrast, cisplatin induced mainly apoptosis and necrosis after 6 h and 24 h, while longer incubation resulted<br />only in necrosis induction. When HeLa cells were incubated with both drugs, autophagy appeared most frequently,<br />although to a smaller extent than that observed after imperatorin administered alone. At the molecular<br />level, autophagy was correlated with the presence of the cleaved form of microtubule-associated protein 1 light<br />chain LC3 — LC3II. It was also accompanied by the inhibition of heat shock proteins Hsp27 and Hsp72 expression.<br />Our results indicate that imperatorin alone, or in combination with cisplatin, is mainly an autopahgy inducer<br />in HeLa cells.There is growing evidence that commonly applied chemotherapy regimens can be improved by introducing<br />new, specific, active and low side-effect drugs, or by combining substances to obtain the required clinical<br />effect. The aim of the present study was to investigate the effects of imperatorin and cisplatin, applied separately<br />or in combination, on apoptosis, necrosis and autophagy induction in the human cervical carcinoma cell line<br />(HeLa). Imperatorin appeared to be a potent autophagy inducer, rather than a necrotic or apoptotic one. In<br />contrast, cisplatin induced mainly apoptosis and necrosis after 6 h and 24 h, while longer incubation resulted<br />only in necrosis induction. When HeLa cells were incubated with both drugs, autophagy appeared most frequently,<br />although to a smaller extent than that observed after imperatorin administered alone. At the molecular<br />level, autophagy was correlated with the presence of the cleaved form of microtubule-associated protein 1 light<br />chain LC3 — LC3II. It was also accompanied by the inhibition of heat shock proteins Hsp27 and Hsp72 expression.<br />Our results indicate that imperatorin alone, or in combination with cisplatin, is mainly an autopahgy inducer<br />in HeLa cells.