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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


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


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)


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


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


Traditional PDT: Drawbacks

  • Non-specificity of sensitization

  • Variable stability of photosensitizers in vivo

  • Toxicity of photosensitizers

  • Limited adaptability


The Big Question

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


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



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 )


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)


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)


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)


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/)


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)


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)


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








Results

HeLa

Bergamot

No UV

Bergamot

+ UV


Results

C6

Bergamot

No UV

Bergamot

+ UV


Results

Signs of Death


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


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


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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