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Nature’s Gold. Essential Oils and Cancer Research Possibilities. Nicole Stevens. What is an Essential Oil?. The Essence of a Plant!. Defense Chemicals. Regulatory Chemicals. Aromatic Chemicals. Life & Death Chemicals. Ancient Knowledge. Egyptians (prior to 1500 B.C.)

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nature s gold

Nature’s Gold

Essential Oils and Cancer Research Possibilities

Nicole Stevens

what is an essential oil
What is an Essential Oil?

The Essence of a Plant!

Defense Chemicals

Regulatory Chemicals

Aromatic Chemicals

Life & Death Chemicals

slide3

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
slide4

Modern Rediscovery

René-Maurice Gattefossé, Ph.D. (1910)

  • Hand badly burned in a laboratory fire—saved 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 body’s nerve pathways
current research
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)
slide6

How PDT Works: Sensitization

2. Drug can stimulate production of cell’s own photosensitive molecules (porphyrins)

Photosensitizer

1. Photosensitive molecules themselves can build up in cell

Cancer Cell

slide7

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

slide8

Traditional PDT: Drawbacks

  • Non-specificity of sensitization
  • Variable stability of photosensitizers in vivo
  • Toxicity of photosensitizers
  • Limited adaptability
slide9

The Big Question

Can Essential Oils be used in Anti-Cancer Photodynamic Therapy?

slide10

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
slide12

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 )

slide13

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)

slide14

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)

slide15

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)

slide16

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/)

slide17

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)

slide18

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)

slide19

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

slide26

Results

HeLa

Bergamot

No UV

Bergamot

+ UV

slide27

Results

C6

Bergamot

No UV

Bergamot

+ UV

slide28

Results

Signs of Death

slide29

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
slide30

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
slide31

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 melatonin. Cancer Lett. 161(1): 1-7.
  • Lemberkovics, E., A. Kery, G. Marzcal, B. Simandi, and E. Szoke. 1998. Acta Pharm Hung. 68(3): 141-9.
  • Egan, C.L., and G. Sterling. 1993. 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 fraction prepared from citrus juices. J Agric Food Chem 47: 128-135.
  • Romano L, Battaglia F, MasucciL, Sanguinetti M, Posteraro B, Plotti G, Zanetti S, Fadda G. 2005. In vitro activity of bergamot natural essence and fucocoumarin-free and distilled extracts, and their associations with boric acid, against clinical yeast isolates. J Antimicrob Chemother 55(1) 110-114)
  • Shao, LX. 2003. Effects of the extract from bergamot and boxthorn on the delay of skin aging and hair growth in mice. Zhongguo Zhong Yao Za Zhi 28(8): 766-9.
  • Souri E, Amin G, Farsam H, Andaji S. 2004. The antioxidant activity of some commonly used vegetables in Iranian diet. Fitoterapia. 75(6): 585-8.
  • Hosseinzadeh H, Karimi GR, Ameri M. 2002. Effects of Anethum graveolens L. seed extracts on experimental gastric irritation models in mice. BMC Pharmacol. 2(1): 21.
  • Zheng GQ, Kenney PM, Lam LK. 1992. Anethofuran, carvone, and limonene: potential cancer chemopreventive agents from dill weed oil and caraway oil. Planta Med. 58(4) 338-41.
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