Exploration of Antiproliferative Activity and Apoptosis Induction of New Nickel(II) Complexes Encompassing Carbazole Ligands

To attest the effectiveness of nickel complexes as anticancer
drug
candidates with minimum side effects, the present investigation describes
the facile synthesis and anticancer activities of nickel(II) complexes
enriched with three derivatives of carbazolone-based benzhydrazone
ligands(L) having a [Ni(L)2] composition. Analytical and
spectral techniques were used to characterize the synthesized Ni(II)
complexes. The single-crystal X-ray diffraction performed for complex 4 confirmed the square planar geometry with a [Ni(κ2-N,O-L)2] arrangement. The MTT assay was carried
out for the complexes to determine in vitro cytotoxicity against cancerous
human-cervical carcinoma, human-colon carcinoma, and non-cancerous
L929 (fibroblast) cells. All three complexes exhibited good toxicity
against the cancer cells with a low IC50 concentration.
Complex 4, containing −OCH3 fragment,
exhibits high lipophilicity and revealed exceptional cytotoxicity
against cancer cells. AO-EB fluorescent staining indicated apoptosis-associated
cell morphological changes after exposure to complex 4. The apoptosis induction was further confirmed by a HOECHST-33342
fluorescent staining technique via chromosomal condensation and nuclear
fragmentation. Further, reactive oxygen species (ROS) and mitochondrial
membrane potential (MMP) mechanistic studies revealed that complex 4 can raise ROS levels and reduce MMP and promote mitochondrial
dysfunction-mediated apoptotic cell death. Further, stimulation of
late apoptosis by complex 4 in cervical cancer cells
was quantitatively differentiated through the staining of phosphatidylserine
externalization by flow cytometry. Furthermore, the ELISA analysis
confirmed that complex 4 induced apoptosis through caspase
activation.