ANTITUMOUR PROPERTIES OF CURCUMA LONGA

INTRODUCTION
▪ Curcumin is the major biological active compound isolated from turmeric or
Curcuma longa linn
▪ Non-toxic natural compound; reported to possess anticancer activities and
used to prevent or treat cancer.
▪ Also known to possess anti-inflammatory activity
(Since cancer often develops under chronic inflammatory conditions
curcumin has the potential to be a preventive measure.)
▪ Curcumin exerts its effect on various stages of cancer development, includes
- Inhibition of Oncogene activation
- Inhibition of Cancer cell proliferation
- Apoptosis evasion
- Prevention of Metastasis
▪ Curcumin has the potential to overcome chemoresistance

Curcuma longa
Curcuma longa is a flowering plant native to Southeast Asia and the Indian
Subcontinent, commonly known as turmeric or Indian saffron
Synonym: Indian saffron, Curcuma, Turmeric, Haldi
Biological Source: Curcumin, commonly known as diferuloylmethane, is a
hydrophobic polyphenol derived from dried rhizomes of perennial herb Curcuma
longa
Family: Zingiberaceace
Parts used: The dried Rhizome or under-ground stem is used for medicinal
purposes
Habitat: India, South-East Asia, China, Thailand, Italy

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FDA has declared turmeric and its active components as GRAS (generally
regarded as safe).
Daily intake of turmeric is recommended as 2.5mg/kg of body weight.
MORPHOLOGY
• They are tuberous rhizomes of perennial herbaceous plants of curcuma longa
▪ The plants reach about 1meter in height
▪ Bear long simple leaves with long petioles
▪ The leaves emerge from the branching rhizomes that lie just below the soil
surface
▪ Older rhizomes are somewhat scaly and brown in color, while young
rhizomes are pale yellow to brown-orange in color
▪ Small yellow orange flowers are borne in the axils of waxy bracts that are
usually pale green or tinged with purple
METHOD OF ISOLATION
Take 20g of turmeric powder in a glass stoppered flask

Add 50ml of pet. Ether

Shake for 30min

Filter (collect the solid residue)

Dry
Dry residue + 50ml of Chloroform

Occasional shaking for 1hr

Filter and filtrate is evaporated to get curcuminoids

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CHEMICAL CONSTITUENTS
▪ Turmeric contains about 5 per cent of volatile oil, resin, abundant
Zingiberaceous starch grains and yellow colouring substances known as
curcuminoids.
▪ The chief component of curcuminoids is curcumin ( 50-60 %)
▪ Curcumin is commonly called as diferuloylmethane.
▪ Hydrophobic Polyphenol, having a pronounced yellow colour
▪ Yellow colour of curcumin is sustained from pH 2.5 to 7 and changes to
reddish colour in alkaline pH
▪ Chemically it is a bis-α, β-unsaturated β-diketone, that exhibits keto-enol
tautomerism

▪ The enolic form dominates in an alkaline form, while keto form dominates in
acidic conditions.
▪ Phenolic and methoxy substitutions on the phenyl ring of Diphenyl heptane
are the cause of formation of compounds namely,
O OH

H3CO OCH3

HO OH

Curcumin I

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 O OH

H3CO H

HO OH

Desmethoxycurcumin (DMC, Curcumin II)

O OH

H H

HO OH

Bisdemethoxycurcumin (BDMC, Curcumin III)

▪ Curcumin I (77%) is major component found
▪ Curcumin II and III constitute approximately 17% and 3% respectively
▪ Curcumin is poorly soluble in water and hydrolyse rapidly in alkaline
solutions
▪ Dissolves well in ethanol, dimethyl sulfoxide, and other organic solvents
▪ The molecular weight of curcumin is 386.37
▪ Melting point is 183oC
▪ It shows a spectrophotometric maximum absorption at 450 nm in methanol.
▪ Fluorescence of curcumin occurs at 524 nm in acetonitrile and 549 nm in
ethanol.

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 STRUCTURE OF CURCUMIN

▪ Curcumin is a beta-diketone where feruloyl groups replace two hydrogens in the

structure. Curcumin is comprised of seven carbon linker chain with 3 functional
groups. These functional groups include an α, β‐unsaturated β‐diketone moiety,
an aromatic O‐methoxy‐phenolic group, and a seven‐carbon linker molecule.
▪ The diketones easily deprotonate themselves and form enolates whereas the α, β‐
unsaturated carbonyl acts as Micheal acceptor and undergoes nucleophilic
addition
▪ The anti-oxidant property of curcumin is caused by its phenolic group, whereas
the carbon linker molecule provides hydrophobicity.
▪ As curcumin is hydrophobic in nature, curcumin has been structurally modified
to increase its biological activity.
▪ Complexes of curcumin with various metals have been synthesised to overcome
the issues associated with curcumin and to make it more biologically potent.
▪ Metals interact with the curcumin ligand, which brings a modification to
curcumin’s overall structure and improves the biological efficacy.
▪ The carbonyl groups at diketone moiety are destabilized due to the metal-ion
coordination, since metals are known as enzyme coactivator, curcumin-metal
complexes can interact with the active sites of enzymes, and induce multiple
cellular processes.
▪ Complexes of curcumin as nanoparticles, liposomes, micelles, phospholipids have
been developed and improved biological efficacy.

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 Metal-Curcumin Interactions

▪ As the α, β‐unsaturated β‐diketo moiety of curcumin is reported to be a strong

chelating agent, it interacts with various metals.
▪ Metals usually bind to the keto-enol (β‐di‐ketone moiety) group of curcumin by
chelation. Chelation is a type of chemical bonding process that involves the
formation of dative covalent bonds between at least one multidentate ligand and
a metal cation.
▪ This chelation bond interaction induces a structural variation to curcumin.
▪ Metals bind either one or two curcumin molecules, the coordination of metals with
curcumin occurs through its enolic group as the enolic proton is replaced by a
metal ion and the o-methoxy phenolic group remains intact in the complexes.
▪ Curcumin-metal complexes reduce the toxicity of metals, the complexation with
certain metals such as Cu2+ and Mn2+ can make for new metal-based antioxidants.
▪ Curcumin-metal complexes with liposomes present enhanced cellular uptake and
generation of reactive oxygen species (ROS) in cancer cells and thus cause
increased cytotoxicity.
▪ Cu2+-Curcumin complex induce DNA photo-cleavage, photocytotoxicity in
cancer cells and enhanced anti-tumor effects.
▪ The encapsulation of Cu2+-Curcumin complex in liposomes was also found to
improve its anti-tumor property.
▪ Platinum-curcumin is another complex which has shown phototoxic and apoptosis
inducing effects in cancer cells.

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ANTI-TUMOR PROPERTIES OF CURCUMIN
▪ Curcumin mainly exerts its anti-tumor activity by arresting the cell cycle
from G1 to S phase.
▪ Curcumin can be used as preventive or treatment agent against cancers
▪ Can be used either as single or combination therapy with chemotherapeutic
agents
▪ Curcumin exhibits biological activities in various stages of carcinogenesis

CHEMOPREVENTIVE PROPERTIES
Carcinogenesis is a multistep process driven by genetic instability. Continuous
exposure to environmental and endogenous genotoxic agents can cause substantial
DNA damage. The damaged molecules can be transmitted during cell division
producing mutated clones that can give rise to the expansion of premalignant cell
population possessing uncontrolled proliferative and invasive properties.
• Curcumin has been established as a chemo preventive agent that has the ability
to suppress or retard the carcinogenic process induced by various chemical
carcinogens.

• In animal models of gastric and colon cancer, curcumin inhibits the

development of cancerous and precancerous lesions induced by N-methyl-N'-

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 nitro-N-nitrosoguanosine (MNNG), a known mutagenic agent causing DNA
methylation.
SUPPRESSION OF ONCOGENES AND UPREGULATION OF TUMOUR
SUPPRESSOR GENES
▪ Genetic instability is linked to the initiation of carcinogenesis.
▪ This irreversible process involves several molecular events that,
- promotes the activity of oncogenes such as myc and ras
- impede the function of tumour suppressor genes such as p53
▪ Curcumin has known to suppress the oncogenes and activate the tumour
suppressor genes in various cancer cell types
Oncogene suppression and tumour suppressor gene activation

Cancer Mechanism

• B cell suppress c-myc

lymphoma

• Human colon Enhances p53 activity

adenocarcinoma

• Human breast Enhances p53 activity

cancer

ANTI-INFLAMMATORY EFFECTS OF CURCUMIN

▪ Epidemiological studies have shown that cancers often develop at sites of
chronic inflammation. This link between inflammation and cancer has been
increasingly recognized as a key factor in cancer development.
▪ There are mainly 2 pathways: Intrinsic and Extrinsic pathway
▪ Extrinsic Pathway: Inflammation that occurs externally and promotes cancer
development.

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 ▪ Intrinsic Pathway: Inflammation driven by genetic instability that creates an
environment conducive to cancer.
▪ Curcumin has been studied for its potential to prevent cancer due to its anti-
inflammatory properties.
▪ NF-κB is a transcription factor that plays a crucial role in the development of
cancer during chronic inflammation. It regulates genes involved in
inflammation and cell proliferation, Curcumin can inhibit the activation of
NF-κB, leading to the suppression of NF-κB-regulated genes.
▪ In mantle cell lymphoma (MCL), a type of cancer, curcumin suppresses NF-
κB, which in turn reduces the expression of cyclin D1 (a protein that promotes
cell cycle progression), leading to cell cycle arrest and apoptosis (cancer cell
death).
INHIBITION OF TUMOR GROWTH AND CELL PROLIFERATION
▪ Cancer cells proliferate excessively, meaning they divide and grow much
more rapidly than normal cells, this is a hallmark of cancer.
▪ In healthy cells, division and growth are tightly regulated and usually require
signals from their environment, such as neighbouring cells and the
extracellular matrix.
▪ Cancer cells, however, can bypass this regulation by producing their own
growth signals, increasing the number of receptors for these signals.
▪ Curcumin can modulate the activity and expression of certain growth factors,
such as Epidermal Growth Factor (EGF).
▪ In prostate cancer cells, curcumin has been found to block the EGF pathway
by downregulating the EGF receptor (EGFR).
▪ It also suppresses the activity of EGFR's tyrosine kinase (an enzyme that
drives cell growth) and inhibits the activation of EGFR by its ligands
(molecules that bind to the receptor to activate it).
▪ Curcumin might help slow or prevent the proliferation of cancer cells by
targeting these specific growth signals and pathways.
INDUCTION OF CANCER CELL APOPTOSIS
▪ Apoptosis is a form of programmed cell death, essential for maintaining tissue
homeostasis by balancing cell proliferation and cell death.
▪ Curcumin can trigger apoptosis through both the intrinsic and extrinsic
pathways.

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 ▪ The intrinsic pathway is activated by internal cellular stress (e.g., DNA
damage). This stress leads to the activation of proapoptotic proteins like
those from the Bcl-2 family, which causes changes in the mitochondria that
release cytochrome c. Cytochrome c then triggers a series of reactions leading
to the activation of caspases (proteins that execute apoptosis) and ultimately
cell death.

▪ The extrinsic pathway is initiated by external signals, like the binding of

death ligands to death receptors on the cell surface. This binding results in
the formation of the death-inducing signaling complex (DISC) and the
activation of caspase-8, leading to apoptosis.

SENSITIZATION OF CANCER CELLS TO CHEMOTHERAPY

▪ Cancer cells often develop resistance to apoptosis (programmed cell death),
making them less responsive to chemotherapy.
▪ Combining curcumin with cisplatin, a common chemotherapy drug for lung
cancer, significantly increases cancer cell death compared to using cisplatin
alone.
▪ Curcumin has been found to increase the production of superoxide anions, a
type of reactive oxygen species (ROS). ROS are chemically reactive
molecules that contain oxygen. While ROS can be harmful in high levels,
they play a crucial role in signaling pathways that regulate cell death.
▪ The increase in ROS leads to oxidative stress within the cancer cells, and
damages key components like DNA,
▪ Downregulates the anti-apoptotic Bcl-2 protein which facilitates the cancer
cell killing by cisplatin.
▪ Bcl-2 blocks programmed cell death
INHIBITION OF CANCER METASTASIS
▪ Metastasis is the process by which cancer cells spread from the primary site
to other parts of the body. This spread is often seen in advanced-stage cancers,
which are more difficult to treat.
▪ Curcumin has been shown in several studies to inhibit critical steps in the
metastatic process, including angiogenesis (formation of new blood vessels),
migration, and invasion of cancer cells.

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 ▪ VEGF is a protein that plays a crucial role in angiogenesis. It stimulates the
formation of new blood vessels, which supply the tumor with nutrients and
allow cancer cells to enter the bloodstream.
▪ MMPs are a family of enzymes that degrade the extracellular matrix (the
network of proteins and other molecules outside cells), which allows cancer
cells to invade surrounding tissues and spread to other parts of the body.
▪ Curcumin inhibits the expression and activity of VEGF (Vascular Endothelial
Growth Factor) and MMPs (Matrix Metalloproteinases) which are essential
for angiogenesis and invasion. By blocking these factors, curcumin reduces
the ability of cancer cells to spread and form new tumours.
Marketed products of curcumin

REFERENCES
1) Pharmacognosy by C.K. Kokate, S.B. Gokale and A.P. Purohit 55th Edition Page no: 14.137-
14.139
2) Prasad S, DuBourdieu D, Srivastava A, Kumar P, Lall R. Metal–curcumin complexes in
therapeutics: an approach to enhance pharmacological effects of curcumin. International
journal of molecular sciences. 2021 Jun 30;22(13):7094.
3) Pongrakhananon V, Rojanasakul Y. Anticancer properties of curcumin. Advances in Cancer
Therapy. 2011 Nov 21.
4) New Look to Phytomedicine by Mohd Sajjad Ahmad Khan Page no: 241-248

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