A novel dialkylamino-functionalized chalcone, DML6, inhibits cervical cancer cell proliferation, in vitro, via induction of oxidative stress, intrinsic apoptosis and mitotic catastrophe

Jenna M. Len, Noor Hussein, Saloni Malla, Kyle McIntosh, Rahul Patidar, Manivannan Elangovan, Karthikeyan Chandrabose, N. S. Hari Narayana Moorthy, Manoj Pandey, Dayanidhi Raman, Piyush Trivedi, Amit K. Tiwari

Research output: Contribution to journalArticlepeer-review

Abstract

In this study, we designed, synthesized and evaluated, in vitro, novel chalcone analogs containing dialkylamino pharmacophores in the cervical cancer cell line, OV2008. The compound, DML6 was selective and significantly decreased the proliferation of OV2008 and HeLa cells in sub-micromolar concentrations, compared to prostate, lung, colon, breast or human embryonic kidney cell line (HEK293). DML6, at 5 µM, arrested the OV2008 cells in the G2 phase. Furthermore, DML6, at 5 µM, increased the levels of reactive oxygen species and induced a collapse in the mitochondrial membrane potential, compared to OV2008 cells incubated with a vehicle. DML6, at 5 µM, induced intrinsic apoptosis by significantly (1) increasing the levels of the pro-apoptotic proteins, Bak and Bax, and (2) decreasing the levels of l the anti-apoptotic protein, Bcl-2, compared to cell incubated with a vehicle. Furthermore, DML6, at 5 and 20 µM, induced the cleavage of caspase-9, followed by subsequent cleavage of the executioner caspases, caspase-3 and caspase-7, which produced OV2008 cell death. Overall, our data suggest that DML6 is an apoptosis-inducing compound that should undergo further evaluation as a potential treatment for cervical cancer.

Original languageEnglish (US)
Article number4214
JournalMolecules
Volume26
Issue number14
DOIs
StatePublished - Jul 2 2021

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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