Induction of G2/M phase arrest and apoptosis by potent antitumor APCA in human cervix carcinoma cells

Abstract

3-(dimethylamino-ethylamino)-8-oxo-8H-acenaphthol[1, 2-b]pyrrole-9-carboxylic acid (APCA), as a potent antitumor compound, showed anticancer activity on a series of established cancer cells. Meanwhile, the cytotoxic effects of APCA were much smaller on normal human cells than that on cancer cells. This study investigated the molecular mechanisms underlying APCA-induced growth inhibition in HeLa cells. The results showed that the APCA-induced cell cycle arrest at G(2)/M phase correlated with cyclinB1 and cyclin-dependent kinase 1 expression downregulation in a p53-independent manner, and also caused an increase in apoptosis, which was confirmed by characteristic morphological changes and increased apoptotic sub-G(1) population. Furthermore, translocation inhibition of nuclear factor-κB, upregulation of Bax, and downregulation of Bcl-2, caspase-3 and caspase-9 activation, and poly-(ADP-ribose) polymerase cleavage were observed in HeLa cells treated with APCA, which indicated that the mitochondrial pathway was involved in the apoptosis signal pathway. In summary, APCA displayed an antitumor effect through cell cycle arrest and apoptotic induction in HeLa cells, which suggested that APCA might have therapeutic potential against cervix carcinoma as an effective lead compound.

Hydroxysteroid Sulfotransferase SULT2B1b Promotes Hepatocellular Carcinoma Cells Proliferation In Vitro and In Vivo

“…The cyclinB1/Cdk1 complex is the primary regulator of the transition from G 2 to M phase [26]. Without synthesis of cyclinB1 before the G 2 /M transition, Cdk1 remains inactive, and the cell cannot enter mitosis, resulting in cell cycle arrest at the G 2 phase [27]. Our data suggests that SULT2B1b inhibition in Hepa1-6 cells can cause G 2 /M phase arrest by decreasing cyclinB1 transcript levels and decreasing its protein stability.…”

Identification and Characterization of MT-1X as a Novel FHL3-Binding Partner

“…The cyclinB1/Cdk1 complex is the primary regulator of the transition from G2 to M phase [36]. Without synthesis of cyclinB1 before the G2/M transition, Cdk1 remains inactive, and the cell cannot enter mitosis, resulting in cell cycle arrest at the G2 phase [37]. Our data suggests that MT-1X inhibition in HepG2 cells can cause G2/M phase arrest by decreasing its protein level.…”

BND-12, a novel nonhaematotoxic naphthalimide derivative, inhibits tumour growth and metastasis of hepatocellular carcinoma

“…Moreover, further investigation showed that BND‐12 could only induce HepG2 cells apoptosis via intrinsic mitochondrial pathway, but not necrosis or autophagy. Based on many naphthalimide derivates, induced tumour cell apoptosis via caspase 3 and caspase 9 activation, mitochondrial pathway‐mediated cell apoptosis may be a main antitumour mechanism for naphthalimide derivates [11] . In our previous study, a novel amonafide analogue NPC‐16 not only induced HepG2 cell apoptosis but also autophagy [12] .…”

“…Based on many naphthalimide derivates, induced tumour cell apoptosis via caspase 3 and caspase 9 activation, mitochondrial pathway-mediated cell apoptosis may be a main antitumour mechanism for naphthalimide derivates. [11] In our previous study, a novel amonafide analogue NPC-16 not only induced HepG2 cell apoptosis but also autophagy. [12] Whereas, Quaquebeke et al [14] reported that a naphthalimide derivative notably induced tumour cell autophagy and senescence, but not apoptosis.…”

“…HCS is based on automated fluorescence microscopy and image analysis, which enables measurement of different targets in a 96‐well format [10] . Previous data demonstrated that some naphthalimide derivates induced tumour cell apoptosis via the influence of lysosomal membrane permeabilization, caspase 3, caspase 9 and mitochondria [6,11] . Thus we simultaneously monitored the changes in nuclear morphology, mitochondrial membrane potential, lysosomal mass/pH and caspase activation using HCS for predictive cytotoxicity.…”