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Title: Nature


1
Natures Gold
  • Essential Oils and Cancer Research Possibilities

Nicole Stevens
2
What is an Essential Oil?
The Essence of a Plant!
Defense Chemicals
Regulatory Chemicals
Aromatic Chemicals
Life Death Chemicals
3
Ancient Knowledge
  • Egyptians (prior to 1500 B.C.)
  • Frankincense and Myrrh considered sacred
  • Sandalwood, clove, lemon used for cleansing,
    antibiotics
  • Middle Eastern Peoples (1500 B.C.)
  • Frankincense and Myrrh mentioned in many
    religious texts
  • Modern steam distillation methods developed by
    Persian doctor
  • Greeks (400 B.C)
  • Hippocrates and Diodes encourage essential oil
    use for health
  • Romans (50 A.D.)
  • De Materio Medica book on healing properties
    of many herbs
  • Europeans (12th Century A.D.)
  • Perfumers and spice traders escape the Black
    Plague by topically applying essential oils

4
Modern Rediscovery
  • René-Maurice Gattefossé, Ph.D. (1910)
  • Hand badly burned in a laboratory firesaved by
    application of Lavender essential oil
  • Develop essential oils for clinical applications
  • Jean Valnet, M.D. (1941)
  • Saves many World War II soldiers in the
    battlefield using essential oils
  • Margaret Maury (1960)
  • Developed methods of applying essential oils
    along the bodys nerve pathways

5
Current Research
  • Stevens 2002 Many essential oils can inhibit
    growth of cancer cells in culture
  • Worked with fairly high concentrations of oil for
    purposes of screening
  • Stevens 2005 Lower concentrations of active
    essential oils
  • Photodynamic Therapy (PDT)

6
How PDT Works Sensitization
2. Drug can stimulate production of cells own
photosensitive molecules (porphyrins)
Photosensitizer
1. Photosensitive molecules themselves can build
up in cell
Cancer Cell
7
How PDT Works Treatment
1. Light excites sensitive molecules
2. Excited molecules damage DNA and proteins
Light
3. Sufficient damage causes cell death
Cancer Cell
8
Traditional PDT Drawbacks
  • Non-specificity of sensitization
  • Variable stability of photosensitizers in vivo
  • Toxicity of photosensitizers
  • Limited adaptability

9
The Big Question
Can Essential Oils be used in Anti-Cancer
Photodynamic Therapy?
10
Essential Oil-based PDT
  • Some essential oils have been shown to have a
    photosensitizing effect following exposure to
    light
  • Only in sensitive individuals
  • Lower incidence of toxicity
  • Highly adaptable (topical application, oral
    administration, inhalation, injection)
  • Possible synergistic effects
  • Kill cancer cells while simultaneously protecting
    normal cells, stimulating immune system, etc.
  • Very little research has been done on the use of
    essential oils in photodynamic therapy against
    cancer cells

11
The Starting Lineup
Why?
12
Traditional and Current Uses
  • Bergamot (Citrus bergamia)
  • Traditional uses bloating and stomachache,
    bladder and blood problems, antimicrobial,
    relaxant, anti-depressant
  • Current uses flavoring and perfumes, cleansing
    and refreshing, relaxant, skin ailments (acne,
    cold sores)
  • Recent Research

Kawaii et al (1999) Bergamot extract causes
differentiation of HL-60 human leukemia
line Romano et al (2005) Bergamot oil active
against Candida yeast infections Shao 2003
Bergamot may play a role in skin and hair growth
(Source www.darbycreeks.org/ Bergamot.jpg )
13
Traditional and Current Uses
  • Dill (Antheum graveolens)
  • Traditional uses analgesic, sleep-inducer,
    halitosis, antispasmodic, relief of intestinal
    spasms, flatulence and cholic
  • Current uses flavoring, anti-microbial,
    digestive ailments, intestinal muscle relaxant,
    possible blood pressure reductant
  • Recent Research

Souri et al (2004) Dill extract showed strong
antioxidant activity Hosseinzadeh et al (2002)
Dill extract protects and soothes intestinal
tract in ulcer-induced mice Zheng et al (1992)
Dill induces detoxifying enzyme GST, may play
important role in chemoprevention
(Source www.milkandhoneyfarm.com/
garden/images/dill.jpg)
14
Traditional and Current Uses
  • Grapefruit (Citrus x paradisi)
  • Traditional uses antiseptic, flavoring and
    perfume, fluid retention, cleansing (both
    internal and external), astringent
  • Current uses dietary supplement and flavoring,
    aromatherapy (for stress and depression),
    antiseptic, disinfectant
  • Recent Research

Negi et al (2001) Grapefruit extract active
against Gram and Gram- bacteria Ortuno et al
(1997)Coumarins from grapefruit give insect and
fungal resistance Robbins et al (1998)
Grapefruit lowers elevated hematocrit levels,
raises low levels
(Source www.botany.hawaii.edu)
15
Traditional and Current Uses
  • Lemon (Citrus limon)
  • Traditional uses antiseptic, antimicrobial,
    improve immune function, improve circulation,
    external cleansing
  • Current uses dietary supplement, stress and
    digestion problems, antidepressant, cleanser and
    stain remover, antimicrobial
  • Recent Research

Masahiro et al (2002) Lemon oil inhibits
elastase, an enzyme which degenerates dermal
elastin Vigushin et al (1998) Limonene from
lemon oil showed low cytotoxicity in Phase I
clinical trials Lis-Balchin and Dean (1997)
Lemon essential oil showed activity against
Listeria
(Source www.illustratedgarden.com, MBG Rare
Books)
16
Traditional and Current Uses
  • Lemongrass (Cymbopogon citratus)
  • Traditional uses antiseptic, cough, antifungal,
    expectorant, analgesic, antimicrobial, heacaches,
    edema, digestion
  • Current uses support proper blood glucose
    levels, external cleanser, fever reducer,
    inflammation, diuretic
  • Recent Research

Formigioni et al (1986) Lemongrass extract did
not produce cytotoxicity in rats Melo et al
(2001) Lemongrass extract helps protect cells
from induced oxidative damage Oyedele et al
(2002) Lemongrass extract is an effective
mosquito repellent Ohno et al (2003) Lemongrass
extract kills Helicobacter pylori
(Source http//davesgarden.com/pf/showimage/1036/
)
17
Traditional and Current Uses
  • Orange (Citrus aurantium)
  • Traditional uses antiseptic, antimicrobial,
    improve immune function, rickets, digestive
    problems, fluid retention, lowering cholesterol
  • Current uses dietary supplement, stress and
    digestion problems, antidepressant, cleanser and
    stain remover, antimicrobial
  • Recent Research

Ramadan et al (1996) Orange oil as a potent
topical anti-fungal agent Vargas et al (1999)
Orange oil has antimicrobial and antioxidant
properties Bodake et al (2002) Orange oil has
chemopreventive effects on the development of
induced tumors Reddy et al (1997) Perillyl
alcohol from orange oil in colon cancer
chemoprevention
(Source www.illustratedgarden.com, MBG Rare
Books)
18
Materials and Methods
  • Cell lines
  • Cancer lines
  • C6 Brain glioma
  • DC4 Breast ductal carcinoma
  • HeLa Cervical adenocarcinoma
  • Jurkat T-cell leukemia
  • Essential Oil Delivery Vehicle
  • DMSO Dimethylsulfoxide

(Source http//www.priondata.org/data/A_DMSO.html
)
19
Materials and Methods
  • Essential Oil concentrations tested
  • 0.01 (100ppm)
  • 0.001 (10ppm)
  • 0.0001 (1ppm)
  • Light wavelength UVA (320-400nm)
  • Viability assay AlamarBlue

1. Non-fluorescent blue solution is added to
cells 2. Live cells will change the blue
substrate into pink fluorescent solution 3.
Fluorescence is read on a spectrophotometer
20
Results
21
Results
22
Results
23
Results
24
Results
25
Results
26
Results
HeLa
Bergamot No UV
Bergamot UV
27
Results
C6
Bergamot No UV
Bergamot UV
28
Results
Signs of Death
29
Conclusions
  • Cell lines respond differently to treatment
  • Some essential oils appear to function as
    photosensitizing agents
  • While some essential oils alone can kill cancer
    cells, in some cases there is a significant
    increase in cell death when treated with light as
    well
  • Generally, response is dose-dependent, and cancer
    cells respond to very small doses

30
Future Research
  • Optimize essential oil concentration
  • More effective oils?
  • May depend on cancer type
  • Minimize non-specific activation
  • Optimize wavelength of PDT treatment
  • May depend on cancer type
  • Most recent research indicates multiple
    wavelengths may be effective
  • Optimize time of treatment
  • Toxicity in non-cancer cells
  • Efficacy in a living system

31
References
  • Girard, J., J. Unkovic, J. Delahayes, and C.
    Lafille. 1979. Phototoxicity of Bergamot oil.
    Comparison between humans and guinea pigs.
    Dermatologica 158(4) 229-43.
  • Kavil, G., and G. Volden. 1984.
    Phytophotodermatitis. Photodermatol. Apr 1(2)
    56-75.
  • Yasui, Y., and T. Hirone. 1994. Action spectrum
    for bergamot-oil phototoxicity measured by
    sunburn cell counting. J Dermatol May
    21(5)319-22.
  • Naganuma, M., S. Hirose, Y. Nakayama, K.
    Nakajima, and T. Someya. 1985. A study of the
    phototoxicity of lemon oil. Arch Dermatol Res.
    278(1) 31-6.
  • Zaynoun, S.T., B.E. Johnson, and W. Frain-Bell.
    1977. A study of oil of bergamot and its
    importance as a phototoxic agent. I.
    Characterization and quantification of the
    photoactive component. Br J Dermatol. 96(5)
    475-82.
  • Zaynoun, S.T., B.E. Johnson, and W. Frain-Bell.
    1977. A study of oil of bergamot and its
    importance as a phototoxic agent. II. Factors
    which affect the phototoxic reaction induced by
    bergamot oil and psoralen derivatives. Contact
    Dermatitis 3(5) 225-39.
  • Lowe, N.J. 1986. Cutaneous phototoxicity
    reactions. Br J Dermatol. Aug 115(Suppl 31)
    86-92.
  • Allen, J.E. 1993. Drug-induced
    photosensitivity. Clin Pharm. Aug 12(8) 580-87.
  • Karbownik, M., D. Tan, L.C. Manchester, and R.J.
    Reiter. 2000. Renal toxicity of the carcinogen
    delta-aminolevulinic acid antioxidant effects of
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    Phytophotodermatitis a visit to Margaritaville.
    Cutis. 51(1) 41-2.
  • Kawaii S, Tomono Y, Katase E, Ogawa K, and Yano
    m. 1999. HL-60 Differentiating Ativity and
    Flavonoid contents of the readily extractable
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  • Romano L, Battaglia F, MasucciL, Sanguinetti M,
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  • Shao, LX. 2003. Effects of the extract from
    bergamot and boxthorn on the delay of skin aging
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