Cervical cancer is mainly caused by the human papillomavirus. The virus alters the host’s histone deacetylase enzyme. The enzyme plays a key role in regulating cell division. The cells, therefore, start dividing at a faster rate.
To treat cervical cancer, we could use Inhibitors of the enzyme. SAHA or Suberoylanilide hydroxamic acid, is one such drug. But it has a lot of side effects.
Ilora Ghosh and her team from JNU, New Delhi chanced on fucoidan, a natural sulphated polysaccharide from marine brown weed, recently touted as a potential anticancer agent.
To find out if fucoidan could inhibit histone deacetylase, Ilora and her team used HeLa cervical cancer cell lines. They cultured the cell lines with fucoidan and SAHA as positive control and found that both inhibited cell growth.
The researchers tested the fucoidan-treated cells for their histone deacetylase activity. There was a substantial reduction in the enzyme activity.
“We also did computer-assisted simulation and found strong binding between fucoidan and a histone deacetylase. The binding was stronger than that between SAHA and the histone deacetylase” says Jogendra Singh Pawar, JNU.
But what are the implications for the cells with reduced histone deacetylase activity? They examined reactive oxidative species in the cells. And found an increase in the reactive oxygen species including superoxides in mitochondria. The cancer cells were under stress.
They also found an increase in autophagosomes – the vesicles that consume parts of the cells from within. Senescence-associated indicators were also high in the fucoidan-treated cells, indicating that apoptosis, programmed cell death, was active, instead of uncontrolled cell division.
“Fucoidan induces oxidative stress in the cancer cells. This could, in turn, act as an epigenetic switch, leading to a reduction in histone deacetylase activity, thus curbing cell growth, suggests Saad Mustafa, JNU.
Whatever be the actual mechanism of action of fuoican, it seems to be less toxic than SAHA. And there are other features that make it attractive as an anticancer drug.
“Fucoidan is absorbed in the intestine after oral intake and it penetrates the blood-brain barrier,” says Ilora Ghosh.
She now looks forward to following up with in-vivo studies.
International Journal of Biological Macromolecules, 181 180–192 (2021);
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