Temozolomide Analog Under Study in Treatment of Ovarian Cancer
Posted: Wednesday, August 7, 2019
Temozolomide-perillyl alcohol conjugate (NEO212), a new temozolomide analog, may be a potential candidate for treating ovarian cancer, as it was found to impair lysosomal function and promote apoptosis. Song et al, of Shandong University in China, published their research findings in the Journal of Experimental & Clinical Cancer Research.
“NEO212 has the potential anticancer property in ovarian cancer cells, as evidence from cell proliferation inhibition, G2/M arrest, DNA damage, xenograft, mitochondrial dysfunction, and apoptosis,” summarized the authors.
To determine the effect of NEO212 on ovarian cancer cell lines, the researchers used flow cytometry analysis along with electron microscopy, immunofluorescence, Western blot, and in vivo studies. NEO212 showed stronger cytotoxicity than its constituents (temozolomide, perillyl alcohol, or combination) by mediating cell-cycle arrest, according to the researchers. This growth inhibition was also observed in vivo, as murine tumors treated with NEO212 grew more slowly than tumors treated with temozolomide and/or perillyl alcohol.
In addition, they noted, NEO212 slowed tumor growth because it was able to initiate cell arrest at the G2/M phase. Growth arrest was mediated by the induction of DNA damage and mitochondrial apoptosis. NEO212 leads to the accumulation of fragmented mitochondria, distorting the overall shape to promote mitochondrial fission and apoptosis.
In cells treated with NEO212, autophagy flux is interrupted, and lysosomal maturity and activity markers are downregulated. Similarly, NEO212 was found to block the nuclear translocation of transcription factor EB, which regulates the steps of lysosomal biogenesis. These results suggest that NEO212 may avoid autophagy-mediated chemoresistance.
Disclosure: The study authors reported no conflicts of interest.