Objectives:
To examine if HIV nosode in 30c dilution (HIV 30c) has therapeutic potential against
lung cancer cells (A549) as compared to WRL-68 normal cells and to elucidate its possible
molecular mechanism of action on DNA replication and apoptosis.
Methods:
Effects of HIV 30c were thoroughly tested for its possible anticancer potential on
A549 cells (lung cancer); WRL-68 normal liver cells served as control. Three doses,
one at LD50 and two below LD-50, were used. Proliferation, migration and senescence
assays were made and generation of reactive oxygen species (ROS) studied by routine
techniques. The ability of HIV 30c to induce apoptosis in A549 cells and its possible
signalling pathway were determined using immunoblots of relevant signal proteins and
confocal microscopy, including studies on telomerase reverse transcriptase (TERT)
and topoisomerase II (Top II) activities, intimately associated with cell division
and DNA replication.
Results:
HIV 30c prevented cancer cell proliferation and migration, induced pre-mature senescence,
enhanced pro-apoptotic signal proteins like p53, bax, cytochrome c, caspase-3 and
inhibited anti-apoptotic signal proteins Bcl2, TERT and Top II, changed mitochondrial
membrane potential and caused externalization of phosphatidyl serine. Thus, it induced
apoptosis as also evidenced from increase in cells with distorted membrane morphology,
nuclear condensation, DNA fragmentation, and ROS, typical of apoptosis in progress.
Conclusion:
HIV 30c nosode has therapeutic potential for inducing cytotoxic effects on A549 cells
as manifested by changes in nuclear condensation, DNA fragmentation, ROS generation
and MMP, and for its inhibitory action on cell proliferation, cell migration, expression
of telomerase reverse transcriptase and Top II genes, and increasing expression of
pro-apoptotic genes.
Graphical abstract
Highlights
• HIV nosode in 30th centesimal dilution induces apoptosis in cancer cells.
• It acts by inhibiting cell proliferation and migration in A549 cells.
• It down-regulates expression of TERT and topoisomerase II enzymes.
• It induces conformational changes in DNA with associated senescence.
Keywords
HIV nosode - Anticancer potential - A549 cells - Telomerase reverse transcriptase
- Topoisomerase-II