Understanding Lung Cancer

compiled by John G. Connor, M.Ac., L.Ac. edited by Barbara Connor, M.Ac., L.Ac.

Table of Contents    
Introduction    
Research on Natural Compounds That May be Suppressive Against Lung Cancer Cell Lines
Research on Natural Compounds That May be Synergistic with Chemotherapeutic Agents Used in Lung Cancer Cell Lines         
References

Introduction

Lung cancer is the leading cause of death among cancers worldwide and non-small cell lung cancer (NSCLC) comprises more than 80% of lung cancer cases.

Although very specific processes underlie malignant transformation, a large number of unspecific influences can initiate the disease including radiation, chemicals, viruses, inflammation, etc. Indeed, it appears that prolonged exposure to almost any provocative agent in the environment can potentially cause cancer. (Seyfried & Shelton 2010)

Individual studies estimate that as many as 69% of US cancer patients employ some type of complementary and alternative medicine, 76% of patients in a study of Midwestern cancer patients and 95% of radiation oncology patients in another study.  (Wargovich et al 2010)

There is an ever growing interest in treatment with natural compounds as an adjuvant cancer therapy along with conventional cancer therapy. (Virk-Baker et al 2010)

For example the combination of a natural VEGF inhibitor along with lower doses of a pharmacological agent may prove helpful in reducing the unwanted side effects of chemotherapy. (Wargovich et al 2010)
 

Research on Natural Compounds That May be Suppressive Against Lung Cancer Cell Lines

1.    Andrographis – Andrographolide, a diterpenoid lactone isolated from a traditional herbal medicine Andrographis paniculata, is known to have the potential to be developed as a chemotherapeutic agent. In order to understand the anti-cancer properties of andrographolide, we examined its effect on migration and invasion in human NSCLC A549 cells. The results of wound-healing assay and in vitro transwell assay revealed that andrographolide inhibited dose-dependently the migration and invasion of A549 cells under non-cytotoxic concentrations. (Lee et al 2010)

2.    Emodin – is a tyrosine kinase inhibitor, a natural anthraquinone, which exhibits anti-cancer effects in lung cancer.  (Chen et al 2009)  

3.    Essential Fatty Acids (EPA & DHA) – Skeletal muscle depletion is associated with reduced plasma (n-3) fatty acids in non-small cell lung cancer patients. (Murphy et al 2010)  

4.    Ginseng – Treatment with red ginseng significantly inhibited both lung tumor multiplicity and tumor load. Our results demonstrated that red ginseng was a potent chemopreventive agent for the prevention of lung tumorigenesis in A/J mice. (Yan et al 2006)

5.    Glucocorticoids – Among the more than 50 different agents tested, several groups of chemicals have shown significant efficacy against mouse lung tumor development, including glucocorticoids and isothiocyanates. Glucocorticoids have proven to be successful during the progression stage of tumor development, whereas isothiocyanates have proven particularly effective in blocking carcinogenesis. (Yan et al 2006)  

6.    Green Tea – EGCG is thought be the most active component in Polyphenon E, but it has to be with other tea catechins to show chemopreventive activity on lung tumorigenesis in aerosolized form. The aerosol delivery of Polyphenon E is an effective method of chemoprevention, which could be considered for further studies in animal models as well as clinical trials. (Fu et al 2009)

7.    Isothiocyanates  – Among the more than 50 different agents tested, several groups of chemicals have shown significant efficacy against mouse lung tumor development, including glucocorticoids and isothiocyanates. Glucocorticoids have proven to be successful during the progression stage of tumor development, whereas isothiocyanates have proven particularly effective in blocking carcinogenesis. (Yan et al 2006)

8.    Milk Thistle (Silibinin) – Silibinin inhibits human nonsmall cell lung cancer cell growth through cell-cycle arrest by modulating expression and function of key cell-cycle regulators. (Mateen et al 2010)  

9.    Ocimum sanctum (Holy Basil) – induces apoptosis in A549 lung cancer cells and suppresses the in vivo growth of Lewis lung carcinoma cells. (Magesh et al 2009)

10.   Pomegranate juice – Oral consumption of pomegranate fruit extract inhibits growth and progression of primary lung tumors in mice. (Khan et al 2007)

11.   Pterostilbene inhibits lung cancer through induction of apoptosis. (Schneider et al 2010)  

12.   Resveratrol – can induce apoptosis in multidrug-resistant human NSCLC SPC-A-1/CDDP cells by down-regulating the expression of survivin. (Zhao et al 2010) Bakuchiol, an analogue of resveratrol exhibited anti-tumor effects on human lung adenocarinoma A 549 cells. (Chen et al 2010)  In another study resveratrol inhibited HO-1 and subsequently MMP-9 and MMP-2 expression in lung cancer cells. The inhibitory effects of resveratrol on MMP expression and invasion of lung cancer cells are, in part, associated with the HO-1-mediated NF-kappaB pathway. (Liu et al 2010)

13.   Vitamin D has important protective effects against lung cancer. These results indicate that there is potential for the use of calcitriol (Vitamin D, 1,25-dihydroxycholecalciferol) as a chemopreventive agent against the development of lung cancer. (Menezes et al 2008) Although there was no overall association between vitamin D and lung cancer risk, women and young participants with a higher level of vitamin D were observed to have a lower lung cancer risk. (Kilkinnen et al 2008)

Research on Natural Compounds That May be Synergistic with Chemotherapeutic Agents Used in Lung Cancer Cell Lines
1.    Astragalus – Astragalus-based Chinese herbal medicine may increase effectiveness of platinum-based chemotherapy when combined with chemotherapy in NSCLC. (McCulloch et al 2006)  

2.    Curcumin – In a laboratory study, vinorelbine alone caused 37.9% cell death in NSCLC cells.  However when pretreated with curcumin 24 hours prior to vinorelbine, the cell death rose to 61.3%, dramatically increasing the treatment effect of vinorelbine (Sen, Sharma et al 2005)

3.    Emodin –Emodin enhances the cytotoxicity induced by gefitinib in two NSCLC cell lines. (Chen et al 2009)

4.    Panax Ginseng – Ginsenoside Rg3 exhibited an inhibitory effect when combined with gemcitabine on angiogenesis and growth of lung cancer in mice. (Liu et al 2009) 

References
1.    Bagchi, Debasis & Harry G. Preuss, Phytopharmaceuticals in Cancer Chemoprevention, CRC Press, Boca Raton, 2005
2.    Beckett, Geoffrey, Simon Walker, Peter Rae & Peter Ashby, Lecture Notes – Clinical Biochemistry, 8th edition, Wiley-Blackwell, Oxford,  2010
3.    Boik, John, Natural Compounds in Cancer Therapy, Oregon Medical Press, Princeton, MN, 2001
4.    Boik, John, Cancer & Natural Medicine, A Textbook of Basic Science and Clinical Research, Oregon Medical Press, Princeton, MN, 1996
5.    Chernecky, Cynthia C, and Barbara J. Berger, Laboratory Tests and Diagnostic Procedures, Saunders, St. Louis, 2008
6.    Davis, Cindy D, Nancy Emenaker and John Milner, “Cellular Proliferation, Apoptosis and Angiogenesis: Molecular Targets for Nutritional Preemption of Cancer, Seminars in Oncology, Vol 37, No. 3, June 2010, pp 243-257
7.    Gullet, Norleena P, Ruhul Arnin, Soley Bayraktar, et al, “Cancer Prevention With Natural Compounds”, Seminars in Oncology, Vol 37, No 3, June 2010, pp 258-281
8.    Heber, David, Editor-in –Chief, Nutritional Oncology, Second Edition, Academic Press, London, 2006
9.    McKenna, Dennis J., PhD,  Kenneth Hones & Kerry Hughes, Botanical Medicines, The Desk Reference for Major Herbal Supplements, Second Edition, The Haworth Herbal Press, New York, 2002
10.   Neal, Michael J., Medical Pharmacology at a Glance, Sixth edition, Wiley-Blackwell, Oxford, 2009
11.   Stargrove, Mitchell, Jonathan Treasure & Dwight L. McKee, Herb, Nutrient, and Drug Interactions, Mosby Elsevier, St. Louis,  2008
12.   Weiss, Rudolf, MD & Volker Fintelmann, MF, Herbal Medicine, Thieme, New York, 2000
13.   Yance, Donald, “Donald Yance’s Eclectic Triphasic Medical System (ETMS): An Integrative Wholistic Approach to Treating and Preventing Cancer”, (Monograph) 2010
14.   Yance, Donald, Herbal Medicine, Healing & Cancer, Keats Publishing, Lincolnwood (Chicago) IL, 1999


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