The cell cycle is tightly regulated by the family of
cyclin-dependent kinases (CDKs). CDKs act as regulatory factors on
serine and
threonine residues by phosphorylating their substrates and
cyclins. CDK‑targeting drugs have previously demonstrated promising effects as
cancer therapeutics both in vitro and in vivo.
Roscovitine, a purine‑derivative and specific CDK inhibitor, has been demonstrated to arrest the cell cycle and induce apoptosis in a number of different
cancer cell lines, including HeLa
cervical cancer cells. In the present study,
roscovitine was able to decrease both the cell viability and cell survival as well as induce apoptosis in a dose‑dependent manner in HeLa cells by modulating the mitochondrial membrane potential. The decrease of anti‑apoptotic
B-cell lymphoma 2 (Bcl‑2) and Bcl-2 extra large
protein expression was accompanied by the increase in pro‑apoptotic
Bcl-2-associated X protein and P53-upregulated modulator of apoptosis expression. The marked decrease in Bcl‑2 following exposure to
roscovitine (20 µM) for 48 h prompted us to determine the autophagic regulation. The outcome revealed that
roscovitine triggered Beclin‑1 downregulation and microtubule-associated light chain 3 cleavage starting from 12 h of incubation. Another
biomarker of autophagy, p62, a crucial
protein for autophagic vacuole formation, was diminished following 48 h. In addition, monodansyl cadaverin staining of autophagosomes also confirmed the autophagic regulation by
roscovitine treatment. The expression levels of different Bcl‑2 family members determined whether apoptosis or autophagy were induced following incubation with
roscovitine for different time periods. Downregulation of pro‑apoptotic Bcl‑2 family members indicated induction of apoptosis, while the downregulation of anti‑apoptotic Bcl‑2 family members rapidly induced autophagosome formation in HeLa cells.