The Clean Living Project Episode 24 - Subconscious
Anti-cancer.pptx
1.
2. DEFINITION
• CANCER:- Cancer is characterized by rapid and uncontrolled
formation of abnormal cells which may mass together to form a
growth or tumor, or proliferate throughout the body, initiating
abnormal growth at other sites.
* ANTI-CANCER DRUGS:- The Drugs that are used in inhibiting
the abnormal cell growth or killing the cancer cells.
3. Stages of the cell cycle
To divide, a cell must complete several important tasks: it must grow, copy its
genetic material (DNA), and physically split into two daughter cells. Cells perform
these tasks in an organized, predictable series of steps that make up the cell cycle.
The cell cycle is a cycle, rather than a linear pathway, because at the end of each
go-round, the two daughter cells can start the exact same process over again from
the beginning.
In eukaryotic cells, or cells with a nucleus, the stages of the cell cycle are divided
into two major phases: interphase and the mitotic (M) phase.
•During interphase, the cell grows and makes a copy of its DNA.
•During the mitotic (M) phase, the cell separates its DNA into two sets and divides
its cytoplasm, forming two new cells.
4. Interphase
Let’s enter the cell cycle just as a cell forms, by division of its mother cell.
Preparation for division happens in three steps:
•G1 phase. During G1phase, also called the first gap phase, the cell grows
physically larger, copies organelles, and makes the molecular building blocks it
will need in later steps.
•S phase. In S phase, the cell synthesizes a complete copy of the DNA in its
nucleus. It also duplicates a microtubule-organizing structure called the
centrosome. The centrosomes help separate DNA during M phase.
•G2phase. During the second gap phase, or G2 phase, the cell grows more,
makes proteins and organelles, and begins to reorganize its contents in
preparation for mitosis. G 2, phase ends when mitosis begins.
The G1, S, and G2, phases together are known as interphase. The prefix inter-
means between, reflecting that interphase takes place between one mitotic (M)
phase and the next.
5. M phase
During the mitotic (M) phase, the cell divides its copied DNA and cytoplasm to make
two new cells. M phase involves two distinct division-related processes: mitosis and
cytokinesis.
In mitosis, the nuclear DNA of the cell condenses into visible chromosomes and is
pulled apart by the mitotic spindle, a specialized structure made out of microtubules.
Mitosis takes place in four stages: prophase (sometimes divided into early prophase
and prometaphase), metaphase, anaphase, and telophase.
In cytokinesis, the cytoplasm of the cell is split in two, making two new cells.
Cytokinesis usually begins just as mitosis is ending, with a little overlap. Importantly,
cytokinesis takes place differently in animal and plant cells.
In animals, cell division occurs when a band of cytoskeletal fibers called the contractile
ring contracts inward and pinches the cell in two, a process called contractile cytokinesis.
The indentation produced as the ring contracts inward is called the cleavage furrow. Animal
cells can be pinched in two because they’re relatively soft and squishy.
6. Cell cycle exit and G0
What happens to the two daughter cells produced in one round of the cell cycle?
This depends on what type of cells they are. Some types of cells divide rapidly, and
in these cases, the daughter cells may immediately undergo another round of cell
division. For instance, many cell types in an early embryo divide rapidly, and so do
cells in a tumor.
Other types of cells divide slowly or not at all. These cells may exit the G1 phase and
enter a resting state called G0 phase. In G 0, a cell is not actively preparing to
divide, it’s just doing its job. For instance, it might conduct signals as a neuron (like
the one in the drawing below) or store carbohydrates as a liver cell. G0 is a
permanent state for some cells, while others may re-start division if they get the right
signals.
How long does the cell cycle take?
Different cells take different lengths of time to complete the cell cycle. A typical human cell
might take about 24 hours to divide, but fast-cycling mammalian cells, like the ones that line
the intestine, can complete a cycle every 9-10 hours when they're grown in culture
7. Apoptosis is a form of programmed cell
death, or “cellular suicide.” It is different
from necrosis, in which cells die due to
injury. Apoptosis is an orderly process in
which the cell's contents are packaged into
small packets of membrane for “garbage
collection” by immune cells. Apoptosis: A
form of cell death in which a programmed
sequence of events leads to the elimination of
cells without releasing harmful substances into
the surrounding area. Apoptosis plays a crucial
role in developing and maintaining the health
of the body by eliminating old cells,
unnecessary cells, and unhealthy cells.
8. MODE OF ACTION OF NATURAL ANTICANCER
DRUGS :
Purine synthesis Pyrimidine synthesis
Ribonucleotides
Deoxyribonucleotides
DNA
RNA
Enzymes Proteins Microtubules
Camptothecin
Etoposide
Block
topoisomerase
functions
Paclitaxel
Vinca
Cholchine
Inhibit the function
of microtubules
9. RECENT ADVANCES OF NATURAL ANTICANCER
AGENTS:-
1.Natural agents have low toxicity.
2.The MOA of recent natural agentsare
* Acts on DNAbases
* Intercalation of DNA
* Inhibit topoisomerases & Proteinkinases
* Induction of Apoptosis (Cell suicide)
3. Many new species are investigated to find out new agents
for treatment of cancer.
4.Cell culture techniques are involved to produce new botanical
therapeutic agents to treat neoplasms
5. Development of QSAR modelling on anti- cancer agents also
produces good therapeutic agents with decreasing toxicity
10. PLANT-DERIVED ANTICANCER AGENTS IN CLINICAL
USE:-
1. First agents that were clinically used are Vinca alkaloids, Vinblastine(VLB) &
Vincristine(VCR),isolatedfromMadagascarperiwinkle.
2. Two clinically active agents, etoposide (VM 26) & teniposide (VP 16-213), semi
syntheticderivativesofepipodophyllotoxinareusedincancertreatment.
3. The use of various parts of T.brevifolia and other Taxus species is widely used in
canertherapy.
4. Anti-cancer drug armamentarium is the class of clinically- active agents derived
from camptothecin, which is isolated from chinese ornamental tree is widely
used.
13. Vinca alkaloids
B. source: Catharanthus roseus
Family: Apocynaceae
Part used: Dried whole plant
Chemical constituent:
Vincristine
Vinblastine
Ajmalicine
Vindesine
14. MODE OF ACTION OF VINCA
• These drugs block the
formation of mitotic spindle
by preventing the assembly
of tubulin dimers into
microtubules.
• They act primarily on the M
phase of cancer cell cycle.
15. Uses ofvinca
In Europe, folk remedy for
diabetes for centuries.
In China, an astringent,
diuretic and cough remedy.
In Central and South
America, homemade cold
remedy to ease lung
congestion and
inflammation and sore
throats
Throughout the Caribbean,
an flower extract to treat
eye irritation and infections
18. MOA of Podophyllum
• Acts by inhibiting
topoisomerase II
• These drugs are most active in
late S and early G2 phase
19. COLCHICUM
B. Source: Colchicum autumnale
Family: Colchicaceae
Part used: seeds and cornsrhizomes & roots
Uses
• Anti cancer
• Antirheumatic
• Anti Leukemic
Mechanism:
Anti proliferative effect through inhibition of microtubule formation
by blocking cell cycle at G2/M phase and triggering apoptosis
Constituents: colchicine, colchicin, colchico-resin
21. Taxanes
• B. source: Taxus
brevifolia/T. baccata
• Family: Taxaceae
• Part used: Stem bark
Uses:
• Ovarian cancer
• Lung carcinoma
• Gastric & Cervical cancers
• Prostate & colon cancer
Chemical constituent:
• Taxol
• Paclitaxel
• Docetaxal
• Becatin 1 and 2 (T. baccata) Taxol
TAXOL
22. MOA of Taxanes
• These drugs act by interfering with mitotic
spindle
• They prevent micotubule disassembly into
tubulin monomers
23. Camptothecin
B. source: Camptotheca acuminata
Family: Nyssaceae
Part used: Dried stem wood
Uses:
Ovarian cancers
Colorectal cancer
Cancer of neck & head
Liver cancer
Chemical constituent:
Camptothecin
Topotecan
Irinotecan
TOPOTECAN
Camptotecan
