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Letters in Drug Design & Discovery


ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Letter Article

Preliminary Analysis of Anti-proliferative, Apoptotic, and Anti-migratory Effects llw-3-6 in Skov-3 Ovarian Cystadenocarcinoma Cell Line

Author(s): Rosalind Gregory-Bass and Leyte L. Winfield*

Volume 17, Issue 10, 2020

Page: [1319 - 1324] Pages: 6

DOI: 10.2174/1570180817666200129142949

Price: $65


Background: Ovarian cancer and ovarian related diseases affect reproductive health. Therapeutic molecules are needed to improve treatment outcomes and overcome drug resistance. The benzimidazole-based sulphonamide LLW-3-6 has both anti-apoptotic and anti-proliferative effects when used to treat prostate, breast, and brain cancer cells.

Objective: The study described herein evaluates the anti-proliferative and anti-migratory effects of LLW-3-6 in SKOV-3 ovarian cystadenocarcinoma cell line.

Methods: Studies were conducted using SKOV-3 cells treated with LLW-3-6. The cell line was propagated and proliferative activity was evaluated by hemocytometric and MTT colorimetric assays. Cellular apoptosis was assessed using caspase-3 spectrophotometric analysis. Lastly, a scratch wound assay was conducted at several concentrations and time points to assess the effect of LLW-3-6 on migration.

Results & Discussion: Proliferative studies suggest, SKOV-3 cells exposed to LLW-3-6 in culture resulted in decreased growth and proliferation of cells in a time and dose-dependent manner. The apoptotic effect of this agent was noted with the confirmed presence of Caspase-3 in a dose and time-dependent manner as well. Preliminary studies also suggest an anti-migratory effect of LLW-3- 6, confirmed by scratch wound analysis.

Conclusion: LLW-3-6 is potentially a chemotherapeutic option for decreasing proliferation and inducing apoptosis in ovarian carcinomas. Additional biological analysis are ongoing to further assess the utility of the molecule and its mechanism of action.

Keywords: Anti-migratory, anti-proliferation, benzimidazole, LLW-3-6, ovarian cancer, SKOV-3.

Graphical Abstract
Winfield, L.L.; Smith, D.M.; Halemano, K.; Leggett, C.S. A preliminary assessment of the structure-activity relationship of benzimidazole-based anti-proliferative agents. Lett. Drug Des. Discov., 2008, 5(6), 369-376.
[] [PMID: 25568641]
Yerokun, T.; Winfield, L.L. LLW-3-6 and celecoxib impacts growth in prostate cancer cells and subcellular localization of COX-2. Anticancer Res., 2014, 34(9), 4755-4759.
[PMID: 25202054]
Payton-Stewart, F.; Tilghman, S.L.; Williams, L.G.; Winfield, L.L. Benzimidazoles diminish ERE transcriptional activity and cell growth in breast cancer cells. Biochem. Biophys. Res. Commun., 2014, 450(4), 1358-1362.
[] [PMID: 24997336]
Yerokun, T.; Winfield, L.L. Celecoxib and LLW-3-6 Reduce survival of human glioma cells independently and synergistically with sulfasalazine. Anticancer Res., 2015, 35(12), 6419-6424.
[PMID: 26637851]
Siegel, R.; DeSantis, C.; Virgo, K.; Stein, K.; Mariotto, A.; Smith, T.; Cooper, D.; Gansler, T.; Lerro, C.; Fedewa, S.; Lin, C.; Leach, C.; Cannady, R.S.; Cho, H.; Scoppa, S.; Hachey, M.; Kirch, R.; Jemal, A.; Ward, E. Cancer treatment and survivorship statistics, 2012. CA Cancer J. Clin., 2012, 62(4), 220-241.
[] [PMID: 22700443]
Wright, J.D.; Chen, L.; Tergas, A.I.; Patankar, S.; Burke, W.M.; Hou, J.Y.; Neugut, A.I.; Ananth, C.V.; Hershman, D.L. Trends in relative survival for ovarian cancer from 1975 to 2011. Obstet. Gynecol., 2015, 125(6), 1345-1352.
[] [PMID: 26000505]
Zeng, C.; Wen, W.; Morgans, A.K.; Pao, W.; Shu, X.O.; Zheng, W. Disparities by race, age, and sex in the improvement of survival for major cancers: Results from the national cancer institute surveillance, epidemiology, and end results (seer) program in the united states, 1990 to 2010. JAMA Oncol., 2015, 1(1), 88-96.
[] [PMID: 26182310]
Tahlan, S.; Kumar, S.; Kakkar, S.; Narasimhan, B. Benzimidazole scaffolds as promising antiproliferative agents: A review. BMC Chem, 2019, 13(1), 66.
[] [PMID: 31384813]
Torres, F.C.; García-Rubiño, M.E.; Lozano-López, C.; Kawano, D.F.; Eifler-Lima, V.L.; von Poser, G.L.; Campos, J.M. Imidazoles and benzimidazoles as tubulin-modulators for anti-cancer therapy. Curr. Med. Chem., 2015, 22(11), 1312-1323.
[] [PMID: 25620093]
Kamal, A.; Nagaseshadri, B.; Nayak, V.L.; Srinivasulu, V.; Sathish, M.; Kapure, J.S.; Suresh Reddy, C. Synthesis and biological evaluation of benzimidazole-oxindole conjugates as microtubule-targeting agents. Bioorg. Chem., 2015, 63, 72-84.
[] [PMID: 26469740]
Xiang, P.; Zhou, T.; Wang, L.; Sun, C-Y.; Hu, J.; Zhao, Y-L.; Yang, L. Novel benzothiazole, benzimidazole and benzoxazole derivatives as potential antitumor agents: Synthesis and preliminary in vitro biological evaluation. Molecules, 2012, 17(1), 873-883.
[] [PMID: 22252503]
Dale, A.G.; Hinds, J.; Mann, J.; Taylor, P.W.; Neidle, S. Symmetric bis-benzimidazoles are potent anti-staphylococcal agents with dual inhibitory mechanisms against DNA gyrase. Biochemistry, 2012, 51(29), 5860-5871.
[] [PMID: 22746203]
Seaton, A.; Higgins, C.; Mann, J.; Baron, A.; Bailly, C.; Neidle, S.; van den Berg, H. Mechanistic and anti-proliferative studies of two novel, biologically active bis-benzimidazoles. Eur. J. Cancer, 2003, 39(17), 2548-2555.
[] [PMID: 14602141]
Chu, S.W.; Badar, S.; Morris, D.L.; Pourgholami, M.H. Potent inhibition of tubulin polymerisation and proliferation of paclitaxel-resistant 1A9PTX22 human ovarian cancer cells by albendazole. Anticancer Res., 2009, 29(10), 3791-3796.
[PMID: 19846910]
Noorani, L.; Pourgholami, M.H.; Liang, M.; Morris, D.L.; Stenzel, M. Albendazole loaded albumin nanoparticles for ovarian cancer therapy. Eur. J. Nanomed., 2014, 6, 227-236.
Masuzzo, P.; Van Troys, M.; Ampe, C.; Martens, L. Taking aim at moving targets in computational cell migration. Trends Cell Biol., 2016, 26(2), 88-110.
[] [PMID: 26481052]
Paul, K.; Sharma, A.; Luxami, V. Synthesis and in vitro antitumor evaluation of primary amine substituted quinazoline linked benzimidazole. Bioorg. Med. Chem. Lett., 2014, 24(2), 624-629.
[] [PMID: 24360999]

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