This document summarizes a study on the effects of cinnamon extract on melanoma cell proliferation and tumor growth. The study found that cinnamon extract treatment inhibited the growth of various cancer cell lines in vitro in a time-dependent manner. It also significantly inhibited melanoma tumor progression in a mouse model. The anticancer effects of cinnamon extract were found to be mediated through the induction of apoptosis in melanoma cells and the downregulation of NFkB and AP1 transcription factors and their target genes. This suggests that cinnamon extract has potential as an anticancer agent through stimulating apoptosis and inhibiting key oncogenic signaling pathways.

2. Herbs: Herbs are the fresh and dried leaves generally of
temperate plants.
Generally herbs are green in color and have a
pleasant taste.
Spices: Spices are the flowers, fruits, seeds, bark, and
roots typically of tropical plants.
Spices are brown, black or red in color with
pungent smell.

3. Brief History:
Spices and herbs are woven in the history of mankind since the early civilization.
Early records indicate that herbs and spices were used as
medicinals in ancient Egypt and as food preservatives in
ancient Rome and Greece.
Herbs and spices continued to be used during the Middle
Ages for flavoring, food preservation, and/or medicinal
purposes.
Today, the business of producing herbs and spices has
become one of the fastest growing industries in
agriculture.

4. Herbs Spices
Source: Nielsen Answers on Demand

5. Herbs Spices
Source: Nielsen Answers on Demand

6. Source: againasttheodds.eu

7. Source: againasttheodds.eu

8. Source: againasttheodds.eu

9. Source: learnaboutcancer.com

10.  According to the Global Oncology Trend Report, released by the IMS Institute for Healthcare
Informatics, global spending on cancer medications rose 10.3 percent in 2014 to $100 billion,
up from $75 billion in 2010.
 The report follows one from IMS Health, which found that overall U.S. spending on drugs
reached $373.9 billion in 2014 – a record high.
Outgoings on drugs for cancer in U.S.A

11.  Fighting cancer is something our body is doing all
the time, not just when one is diagnosed with the
disease.
 Some culinary herbs and spices are particularly
rich in cancer preventive and cancer-fighting
substances.
 Herbs and spices serve as inhibitors of carcinogen
bio-activation, decrease free radical formation,
suppress cell division and promote apoptosis in
cancerous cells.
 Dragland et al. 2003 suggested that the addition
of about 1 g/day of herbs and spices to one’s diet
can significantly contribute to total antioxidant
intake (>1 mmol) and offers a better source of
antioxidants than many food items.
5 CANCER-FIGHTING
HERBS
BASIL
PARSLEY
RED CLOVER
ROSEMARY
CHICKWEED

12.  Spices and herbs may be a key to determine the balance between pro- and anticancer
factors that regulate risk and tumor behavior.
 Multiple factors may influence the need for spices for reducing the risk of cancer or
changing the biological behavior of cancer cells.
Herbs Spices
Antimicrobial
Antioxidant
Anti-inflammatory
Mediators
Anti-carcinogenic
Anti-tumorigenic
Harmful Microbes
Oxidation
Pro inflammatory-
Mediators
Carcinogens
Tumorigenic-
Compounds
Low ------------------ Cancer ---------------- High
Dietary factors including herbs and spices
Herbs, Spices and Cancer

13. Abdulaziz Alsemari,Fahad Alkhodairy,Ahmad Aldakan,Mai Al-Mohanna,
Eman Bahoush,Zakia Shinwari andAyodele Alaiya
(2014)

14.  Trigonella foenum graecum: Fenugreek
 T-cell lymphoma: Lymphoma is the most common blood
cancer. Lymphoma occurs when cells of the immune system called
lymphocytes, a type of white blood cell, grow and multiply uncontrollably.
The body has two main types of lymphocytes that can develop into
lymphomas: B-lymphocytes (B-cells) and T-lymphocytes (T-cells).
 Proteomics: The study of proteins and their functions.
 Apoptosis: The death of cells that occurs as a normal and
controlled part of an organism's growth or development.

15.  The current in vitro studies were prompted by the clinical profile of a previously
reported case of primary CNS(Cerebral) T cell lymphoma.
 Brain MRI with contrast was performed and revealed numerous cerebellar-
enhancing lesions.
 The patient initially went into clinical remission for 37 months after chemotherap
y and radiotherapy.
 After three years of remission, the patient’s disease relapsed with intermittent
weakness in her left arm and deviation of her mouth to the left.

16.  The family decided to treat their child with concentrated extract of fenugreek,
boiled in regular water. The approximate daily treatment amount was 8 g of
fenugreek seeds, over the course of six months.
 Repeat brain MRI three months later showed significant improvement in the intra
cerebral lesion.
 The subsequent brain MRI after six months showed complete resolution of the
relapsed lesion.
 In this research demonstrated the selective cytotoxic effects of fenugreek extract
in vitro on a panel of cancer cell lines, and a proteomics analysis of fenugreek.

17. Brain MRI shows enhanced
lesion in the front parietal lesion.
Brain MRI with contrast
shows complete resolution of
relapsed lymphoma.

18. Research Questions
 Does fenugreek has selective cytotoxic effects against cancer
cells?
 Does fenugreek selectively induces apoptosis in cancer and
normal cells?
 Is there a significant difference between protein patterns of four
different regional fenugreek samples?

19. Cell culture:
T-cell lymphoma (TCP), B-cell lymphomas, Thyroid Papillary carcinoma
(FRO) and human breast cancer (MCF7)
Cells were cultivated at 37°C and 5% CO2 in Dulbecco’s MEM (DMEM)
containing 5% fetal bovine serum, 3 mM glutamine and antibiotics
Fenugreek extraction:
Fenugreek seeds were extracted in water, filtered, concentrated and
reconstituted to a working stock concentration of 50 mg/ml
Cells were exposed to fenugreek extract at
different concentrations (100 ug/ml, 200 ug/ml and 300 ug/ml) and at
different time points (0, 24, 48, 72 and 96 hrs).
Lymphoma

20. Does fenugreek has selective cytotoxic effects against cancer cells?
 Cells were seeded onto a
96-well plate at a density of
5000 cells/well.
 Incubated at 37°C for
different time points (0, 24, 4
8, 72 and 96 hrs.) in a
titrated medium containing
different concentrations
(100 ug/ml, 200 ug/ml and
300 ug/ml) of fenugreek
extract.
96-Well Plate

21. Does fenugreek selectively induces apoptosis in cancer and normal cells?
 Approximately 5 × 105 cells
were seeded and cultured in
60 mm plates.
 Incubated at 37°C for 72 hours
in a titrated medium containing
different concentrations of
fenugreek extract.
 Thereafter, cells were stained
with Propidium Iodide (PI) and
Annexin V, using Vybrant
Apoptosis Assay kit.
Flow cytometric graphs of T-cell lymphoma without fenugreek treatment (A) and when
treated with 300 μg/ml of Fenugreek, for 24, and 72 hours, B and C respectively.

23. Is there a significant difference between protein patterns of four different
regional fenugreek samples?
 Seeds from four different regions were grounded and protein was extracted.
 2-D Electrophoresis was used to determine the protein patterns.
Representative 2-DE gels derived from all the 4 different regional Fenugreek samples (A): Fenugreek
taken by the patient. (B, C and D): Fenugreeks form other regions.

24. Sample pairs Correlation
Group correlation among pairs of A and B 0.37 (n= 3 pairs)
Group correlation among pairs of A and D 0.41 (n= 3 pairs)
Group correlation among pairs of A and C 0.36 (n= 3 pairs)
Group correlation among pairs of B and D 0.86 (n= 3 pairs)
Group correlation among pairs of B and C 0.83 (n= 3 pairs)
Group correlation among pairs of D and C 0.88 (n= 3 pairs)
Correlation analysis of pairs of 2-DE gels of fenugreek samples from four
different regions A, B, C and D. Note the poor correlation between pairs of
fenugreek from region A vs. B/C/D, compared with good correlation
among pairs of D/C,B/D, C/B

25.  First human case in which established malignant CNS cancer showed
regression, then disappearing of the cancer lesion with daily use of fenugreek
extract.
 Analysis of fenugreek extract indicated the presence of several compounds with
anticancer properties, including gingerol, cedrene, zingerone, vanillin and
eugenol.
 Biologically active agents in fenugreek may vary based on geographical
environments.
 However, these exciting results obviously warrant additional study, including
further drug characterization and development.

26. Pratima Nangia-Makker, Larry Tait, Malathy P.V. Shekhar, Eduardo
Palomino, Victor Hogan, Marie P. Piechocki, Tatsuyoshi Funasaka and
Avraham Raz (2007)

27.  OG: Ocimum gratissimum (holy basil)
 COX-2: enzyme responsible for inflammation
 MDA-MB-435 and MDA-MB-231: human breast
cancer cells
 EIII8 and DCIS.com: human preneoplastic breast
cancer cells
 BAMEC: bovine adrenal medulla endothelial cells

28. “Holy Basil” or “Tulsi”
Anti-oxidant, anti-carcinogenic, radio-prot
ective and free radical scavenging
properties
No detailed studies on effects on human
cancers
Active constituents thought to be
responsible for medical action:
 Eugenol, Apigenin, and Ursolic Acid

29. Purpose:
 To analyze the impact of Ocimum on tumor
growth, angiogenesis, and metastasis related
properties
 To compare the analysis of eugenol, apigenin,
and ursolic acid

30. Research Questions:
 What are the effects of Ocimum on human breast
cancer?
 How do eugenol, apigenin, and ursolic acid
compare in terms of tumor cell migration and
3D tube formation?

31. Aqueous extracts prepared from mature OG
leaves
Iceberg lettuce as control, prepared similarly to
OG leaf extract
3D growth of DCIS.com and EIII8 cells
MDA-MB-435 and MDA-MB-231 were gifted
Iceberg lettuce as control, prepared similarly to
OG leaf extract

32. Cell viability, cell proliferation, anchorage
independent growth, three-dimensional growth and
tube formation assay, induction of COX-2
expression and western blot analysis, angiogenesis
assay, tumor growth in nude mice,
immunohistochemical analysis, TUNEL assay, high
performance liquid chromatography, and statistical
analysis

33. Figure I: Growth curve of MDA-MB-231 cells
in presence of OG extract
a) Range between 10 and 15,000
b) Range between 15 and 20,000
Figure II: Anchorage independent growth of
MDA-MB-231 cells on soft agar in presence
of OG extract
a) Control, b) .1% OG extract, c) histogram
representing colony forming efficiency at
various concentrations of OG extract

34. Figure I: Effect of OG extract and components on tube formation of EIII8 cells.
(a) control untreated; (b) 0.05% OG extract (w/v); (c) 0.1% OG extract (w/v);
(d) 625 μM eugenol, (e) 10 μm ursolic acid; (f) 18 μm apigenin, (g) 0.01%
ethanol; (h) 1.25 mM KOH.
International
Journal of
Cancer
Volume 121,
Issue 4, pages 88
4-894, 16 APR 20
07 DOI: 10.1002/i
jc.22733
http://onlinelibrar
y.wiley.com/doi/1
0.1002/ijc.22733/f
ull#fig3

35.  Aqueous extract of Ocimum leaves inhibit tumor growth and
angiogenesis by
 Tumor cell proliferation
 Migration
 Morphogenesis
 Stromal apoptosis
 Induction of COX-2
 Inhibitory properties not due to any 1 of 3 active components
 Due to undescribed component or combination of components?

36. Ho-Keun Kwon, Ji-Sun Hwang, Jae-Seon So,Choong-Gu Lee, Anupama Sahoo,
Jae-Ha Ryu, Won Kyung Jeon,Byoung Seob Ko,Chang-Rok Im, Sung Haeng Lee,
Zee Yong Park andSin-Hyeog Im (2010)

37.  NFkB: It is a protein complex which controls
transcription of DNA, cytokine production and
cell survival.
 AP1: It regulates gene expression in response to
stimuli like cytokines, growth factors, stress &
bacterial & viral infections. It controls cell growth,
proliferation & apoptosis.

38.  Cinnamomum cassia bark is the outer skin of a tree .
 Its extract contains essential oils (cinnamic aldehyde and cinnamyl aldehyde),
tannin, mucus and carbohydrates.
 It has got the several biological functions such as anti-oxidant, anti-microbial,
anti-inflammation, anti-diabetic effects and anti-tumor activity.
 Tumor cells are generally resistant to apoptosis. Thus, killing the tumor cells by
stimulating the pathway of apoptosis is the best way to develop anticancer
agents.
 NFkB and AP1 play important roles in tumor development.
 It is reported that anticancer effect of cinnamon extract is associated with
modulation of angiogenesis and effector function of CD8* T cells

39. Research Questions:
Does cinnamon extract inhibit tumor cell proliferation and
induced tumor cell death?
Does cinnamon extract induces active cell death of
melanoma cells?
Does cinnamon extract inhibits the melanoma growth by
inhibiting NFκB and AP1?

40. Treatment of cinnamon extract inhibits the growth of various cancer cells. Cinnamon
(0.5 mg/ml) was treated for 0, 48 and 72 hrs to cancer cell lines (Hela; cervical cancer, Caco2; colon
cancer, Clone M3; melanoma and B16F10; melanoma). After treatment of cinnamon extract,
(A) morphological changes of each cancer cell lines were monitored by microscopic observation.
(B) Proliferation and viability of cancer cells were measured by cell viability assay at the indicated
time points.

41. Oral administration of cinnamon extract significantly
inhibits melanoma progression in vivo
Oral administration of cinnamon extract inhibits melanoma growth in vivo

42. Cinnamon extract treatment induces active cell death in melanoma cells. At the indicated time
periods after treatment of cinnamon extract, cells were stained with Annexin V and 7-ADD. Double
positive (Annexin V+ and 7-ADD+) (A) or Annexin V+ positive (B) populations were analyzed by
FACS. Gene expression (C) and protein (D) level of pro-apoptotic molecules such as Bad, Bim, Bax and
Bak were measured by quantitative real-time PCR or immunoblotting, respectively.

43. Cinnamon extract treatment down-regulates the levels of NFκB and AP1 and their target genes

44. Anti-tumor effect of cinnamon extract is linked to the
reduced levels of NFκB and AP1 in vivo melanoma model
Cinnamon extract treatment induces tumor apoptosis by decreasing the
levels of NFκB and AP1 and their target genes.

45.  The extracts of cinnamon inhibited the various tumor cell
growths in vitro and suppressed in vivo melanoma
progression.
 The cinnamon extract mediate the anti-cancer effect by
apoptosis induction and NFkB & AP1 blockade.

47. Article Main Finding Strengths Weaknesses Future Studies
Impact of Ocimum on
Breast Cancer Tumor
Growth
 Aqueous extract of Ocim
um leaves inhibit tumor g
rowth and angiogenesis
 Inhibitory properties not d
ue to any 1 of 3 active co
mponents
 Comparing the analysis o
f active components: eug
enol, apigenin, and ursoli
c acid
 Use of human breast can
cer cells
 Individual active compon
ents had no affect
 Isolate active
components
The selective cytotoxic anti
-cancer properties and prot
eomic analysis of Trigonell
a Foenum-Graecum
 Fenugreek has selective
cytotoxic effects against
cancer cells.
 Observed a significant de
gree of heterogeneity in t
he protein expression bet
ween samples
 First human study to sh
ow anticancer propertie
s of fenugreek in patient
with relapsed CNS-lymp
homa
 Comparing the protein c
ontent between fenugre
ek samples
 Geographical Locations
of samples were not spe
cified.
 Limited sample size.
 A more rigorous scientific
evaluation, such as a
clinical trial, is obviously
warranted before the
anti cancer properties of f
enugreek can be confirm
ed.
Cinnamon extract induces
tumor cell death through in
hibition of NFkB and AP1
 Extracts of cinnamon
inhibit the tumor cell
growths in vitro and
suppressed in vivo
melanoma progression.
 The extract of cinnamon
mediates the anti-cancer
effect by apoptosis
induction and NFkB and
AP1 blockade.
 Use of human cancerou
s cells.
 The temperature of wate
r used for extraction is n
ot mentioned.
 The human melanoma
cells are not used.
 Further study on human
melanoma cells can be
done.
 Mechanism of action of
cinnamon can be
studied.

48. DNA
Repair
Carcinogen
Metabolism
Inflammatory
Response
Carcinogen
Metabolism
Hormonal
Regulation
DifferentiationApoptosis
Cell
Cycle

49.  Currently available data are intriguing, the effective exposures needed to
bring about the desired outcome(s), and what interactions (both positive
and negative) exist with other components of the diet or with medications
that an individual may regularly consume
 Clarification is also needed regarding which types of cells respond to
various herbs, spices, and their bioactive components and further
exploration of the potential for gender-based differences in response.

50. Dragland S, Senoo H, Wake K, Holte K, Blomhoff R. Several culinary and medicinal herbs
are important sources of dietary antioxidants. J Nutr. 2003;133:1286–90.