Lopinavir
Fights HPV in Cervical Cancer Cells
SUMMARY
The HIV protease inhibitor lopinavir (the main drug in
Kaletra) blocked viral proteasome activitation and selectively
killed pre-cancerous cervical cells infected with human
papillomavirus (HPV). |
As
reported in the May
3, 2011, advance online edition of Antiviral Therapy,
Gavin Batman and Ian Hampson from the University of Manchester
in the U.K. and colleagues tested lopinavir in HPV-infected
SiHa cervical carcinoma cells in a laboratory study.
In addition to cervical cancer, high-risk HPV types can also
cause anal cancer, genital cancers, and mouth and throat cancers.
Research has shown that HIV
positive people are more likely to carry high-risk HPV
and more often develop pre-cancerous lesions that can progress
to cancer if left untreated.
Below is an edited excerpt from a
press release issued by the University of Manchester describing
the study and its findings.
HIV
Drug Could Prevent Cervical Cancer
May 3, 2011 -- A widely used HIV drug could be used to prevent
cervical cancer caused by infection with the human papillomavirus
(HPV), say scientists.
University of Manchester researchers, working with colleagues
in Canada, have discovered how the antiviral drug lopinavir
attacks HPV by switching on a natural viral defense system
in infected cells.
The study, published in the journal Antiviral Therapy,
builds on the team's previous work in 2006 that first identified
lopinavir as a potential therapeutic for HPV-related cervical
cancer following laboratory tests on cell cultures.
"Since publishing our earlier work, we have now found
that lopinavir selectively kills HPV-infected, non-cancerous
cells, while leaving healthy cells relatively unaffected,"
said Dr Ian Hampson, from Manchester's School of Cancer and
Enabling Sciences.
"This is a very significant finding as these cells are
not cancer cells but are the closest thing to being like the
cells found in a pre-cancerous HPV infection of the cervix.
In addition we were also able to show that lopinavir kills
these HPV-infected cells by re-activating a well-known antiviral
system that is suppressed by HPV."
In many developing countries, HPV-related cervical cancer
is still one of the most common women's cancers accounting
for approximately 290,000 deaths per year worldwide. The same
virus also causes a significant proportion of cancers of the
mouth and throat in both men and women and this disease is
showing an alarming increase in developed countries, such
as the UK, where it is now more than twice as common as cervical
cancer.
Although in the developed world vaccination programs against
HPV are well underway, these are not effective in women already
infected with HPV. Furthermore, the current vaccines do not
protect against all types of HPV and they are expensive, which
will limit their use in countries with limited resources.
A cheap and preferably self-administered treatment that could
eliminate early-stage HPV infections before these have developed
into cancers would therefore have distinct health advantages.
Dr Hampson said: "Our results suggest that for this drug
to work against HPV it would be necessary to treat virus-infected
cells of the cervix with roughly 10-15 times the concentration
that is normally found in HIV-infected patients taking lopinavir
as tablets. This implies that, for this treatment to work,
it would need to be locally applied as a cream or pessary."
Co-author on the paper, Dr Lynne Hampson, added: "These
results are very exciting since they show that the drug not
only preferentially kills HPV-infected non-cancerous cells
by re-activating known antiviral defense systems, it is also
much less toxic to normal non-HPV infected cells.
"Lopinavir is obviously safe for people to take as tablets
or liquid but our latest findings provide very strong evidence
to support a clinical trial using topical application of this
drug to treat HPV infections of the cervix."
5/6/11
Reference
G
Batman, AW Oliver, I Zehbe, et al. Lopinavir up-regulates
expression of the antiviral protein ribonuclease L in human
papillomavirus-positive cervical carcinoma cells. Antiviral
Therapy (abstract).
May 3, 2011 (Epub ahead of print).
Other Source
University
of Manchester. HIV Drug Could Prevent Cervical Cancer. Press
release. May 3, 2011.
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