2. introduction
•The most common form is
hepatocellular carcinoma (HCC) ("Liver
Cancer").
•HCC is the third leading cause of
cancer-related deaths worldwide.
3. doxorubicin
• an anthracycline.
• doxorubicin works is by blocking an enzyme
called topo isomerase 2 that cancer cells need
to divide and grow.
4. cisplatin
• It does this by binding together the strands of
the cells' genetic material, DNA. DNA is needed
for growth and multiplication of cells.
Cisplatin damages the DNA inside the cancer
cells and so prevents them from multiplying
• Alkaylating agent
• These platinum complexes react in the body,
binding to DNA and causing the DNA strands to
crosslink, which ultimately triggers cells to die in
a programmed way
5. Drug-Tetrahydro cannabis
(EXPERIMENTS)
• THC is a potent inducer of apoptosis in the human HCC cell
lines HepG2 and HuH-7(Hep G2 is a perpetual cell line which
was derived from the liver tissue of a 15-year-old Caucasian
American male with a well-differentiated hepatocellular carcinoma.
These cells are epithelial in morphology, have a modal chromosome
no. of 55. The cells secrete a variety of major plasma proteins, e.g.,
albumin, transferrin, and the acute-phase proteins fibrinogen, alpha
2-macroglobulin, alpha 1-antitrypsin, transferrin, and plasminogen.)
The effect was mediated by CB2, but not CB1, receptors.
• THC increased the lipidated form of microtubule-associated
protein 1 light chain 3α (LC3), an autophagy-related
molecule which attaches to autophagosomes after
autophagy becomes stimulated.
6. • Autophagosomes are organelles that absorb
cellular debris or components ("Lippincott-
Schwartz").
• They transfer these components to lysosomes
via fusion, where they are digested. By
influencing this process, THC contributed to
dynamic autophagy in both cell lines.
7. • One of the pathways leading to autophagy was dependent on
endoplasmic reticulum (ER) stress. The first step appeared to be an
increase in ceramide biosynthesis, which is associated with ER stress
.
• there was increased phosphorylation of adenosine monophosphate-
activated protein kinase (AMPK). This kinase is an important
intracellular nutrient status sensor and key regulator of autophagy.
Its enhanced activation contributed to cannabinoid-induced
autophagy and apoptosis;
• the role of the PPAR-γ receptor in THC-induced apoptosis of HepG2
and HuH-7 cells . PPAR-γ is a receptor found inside cells that helps
regulate lipid metabolism and insulin sensitization. Its activation is
associated with growth inhibition and apoptosis of numerous tumor
cells
• Peroxisome proliferator-activated receptor gamma (PPAR-γ or
PPARG), also known as the glitazone receptor,
8. • To demonstrate effectiveness in vivo, mice
were treated daily with 15mg/kg of THC for 15
days.
• The cannabinoid "almost totally blocked the
growth of HepG2 cell-derived tumors." Similar
effects were seen in HuH-7 tumors. Increased
AMPK phosphorylation.