Ethanolic Extract of Marsdenia condurango Ameliorates Benzo[a]pyrene-induced Lung Cancer of Rats
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Objectives: Condurango is widely used in various systems of complementary and alternative medicines (CAM) against oesophageal and stomach ailments including certain types of cancer. However, until now no systematic study has been conducted to verify its efficacy and dose with proper experimental support. Therefore, we examined if ethanolic extract of Condurango could ameliorate benzo[a]pyrene (BaP)-induced lung cancer in rats, in vivo to validate its use as traditional medicine. Methods: Fifteen male and 15 female SD rats were treated with 0.28 mg/kg of SBV (high-dosage group) and the same numbers of male and female SD rats were treated with 0.2 mL/kg of normal saline (control group) for 13 weeks. We selected five male and five female SD rats from the high-dosage group and the same numbers of male and female SD rats from the control group, and we observed these rats for four weeks. We conducted body-weight measurements, ophthalmic examinations, urinalyses and hematology, biochemistry, histology tests. Results: A histological study revealed gradual progress in lung tissue-repair activity in Condurango-fed cancer-bearing rats, showing gradual tissue recovery after three months of drug administration. Condurango has the capacity to generate ROS, which may contribute to a reduction in anti-oxidative activity and to an induction of oxidative stress-mediated cancer cell-death. Condurango-activated pro-apoptotic genes (Bax, caspase-3, caspase-9, p53, cytochrome-c, apaf-1, ICAD and PARP) and down-regulated antiapoptotic-Bcl-2 expression were noted both at mRNA and protein levels. Studies on caspase-3 activation and PARP cleavage by western blot analysis revealed that Condurango induced apoptosis through a caspase-3-dependent pathway. Conclusion: The anticancer efficacy of an ethanolic extract of Condurango for treating BaP-induced lung cancer in rats lends support for its use in various traditional systems of medicine.
Abstract
Objectives: Condurango is widely used in various systems of complementary and alternative medicines (CAM) against oesophageal and stomach ailments including certain types of cancer. However, until now no systematic study has been conducted to verify its efficacy and dose with proper experimental support. Therefore, we examined if ethanolic extract of Condurango could ameliorate benzo[a]pyrene (BaP)-induced lung cancer in rats, in vivo to validate its use as traditional medicine. Methods: Fifteen male and 15 female SD rats were treated with 0.28 mg/kg of SBV (high-dosage group) and the same numbers of male and female SD rats were treated with 0.2 mL/kg of normal saline (control group) for 13 weeks. We selected five male and five female SD rats from the high-dosage group and the same numbers of male and female SD rats from the control group, and we observed these rats for four weeks. We conducted body-weight measurements, ophthalmic examinations, urinalyses and hematology, biochemistry, histology tests. Results: A histological study revealed gradual progress in lung tissue-repair activity in Condurango-fed cancer-bearing rats, showing gradual tissue recovery after three months of drug administration. Condurango has the capacity to generate ROS, which may contribute to a reduction in anti-oxidative activity and to an induction of oxidative stress-mediated cancer cell-death. Condurango-activated pro-apoptotic genes (Bax, caspase-3, caspase-9, p53, cytochrome-c, apaf-1, ICAD and PARP) and down-regulated antiapoptotic-Bcl-2 expression were noted both at mRNA and protein levels. Studies on caspase-3 activation and PARP cleavage by western blot analysis revealed that Condurango induced apoptosis through a caspase-3-dependent pathway. Conclusion: The anticancer efficacy of an ethanolic extract of Condurango for treating BaP-induced lung cancer in rats lends support for its use in various traditional systems of medicine.
참고문헌 (27)
- Mantena SK., "Berberine inhibits growth, induces G1 arrest and apoptosis in human epidermoid carcinoma A431 cells by regulating Cdki-Cdk-cyclin cascade, disruption of mitochondrial membrane potential and cleavage of caspase 3 and PARP", Carcinogenesis, 27(10), pp.2018~2027 (2006)
- "Department of Health, Health and National Health Insurance Annual Statistics Information Service" (2009)[URL]
- "Acupuncture (PDQ)"[URL]
- Bishop JA., "Accurate classification of non-small cell lung carcinoma using a novel microRNA-based approach", Clin Cancer Res, 16(2), pp.610~619 (2010)
- Kometani T., "Benzo a, pyrene promotes proliferation of human lung cancer cells by accelerating the epidermal growth factor receptor signaling pathway", Cancer Lett, 278(1), pp.27~33 (2009)
- Sticha KR., "Effects of benzyl isothiocyanate and phenethyl isothiocyanate on benzo a, pyrene metabolism and DNA adduct formation in the A", J mouse, 2000, pp.21(9), 1711~1719
- Tseng CL., "Targeting efficiency and biodistribution of biotinylated-EGF-conjugated gelatin nanoparticles administered via aerosol delivery in nude mice with lung cancer", Biomaterials, 29(20), pp.3014~3022 (2008)
- Koshkina NV., "Paclitaxel liposome aerosol treatment induces inhibition of pulmonary metastases in murine renal carcinoma model", Clin Cancer Res, 7(10), pp.3258~3262 (2001)
- 최원형, "Effects of Fraction Obtained From Korean Corni Fructus Extracts Causing Anti-Proliferation and p53-Dependent Apoptosis in A549 Lung Cancer Cells", NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL, 63(1), pp.121~129 (2011), LAWRENCE ERLBAUM ASSOC INC-TAYLOR FRANCIS
- Rostock M., "Classical homeopathy in the treatment of cancer patients--a prospective observational study of two independent cohorts", BMC Cancer, 11, pp.19~ (2011)
- Staunton MJ., "Apoptosis : basic concepts and potential significance in human cancer", Arch Pathol Lab Med, 122(4), pp.310~319 (1998)
- Sikdar S., "Ethanolic extract of Condurango(Marsdenia condurango)used in traditional systems of medicine including homeopathy against cancer can induce DNA damage and apoptosis in non small lung cancer cells, A549 and H522, in vitro", International J Genuine Traditional Medicine(TANG), 3(1), pp.43~52 (2013)
- Paul S., "Anticancer potentials of root extract of Polygala senega against benzo a, pyrene-induced lung cancer in mice", Zhong Xi Yi Jie He Xue Bao, 9(3), pp.320~327 (2011)
- Karmakar SR., "Anti- carcinogenic potentials of a plant extract (Hydrastis canadensis), I. Evidence from in vivo studies in mice (Mus musculus)", Asian Pac J Cancer Prev, 11(2), pp.545~551 (2010)
- Kundu S., "Cadmium induces lung inflammation independent of lung cell proliferation : a molecular approach", J Inflam, 6, pp.19~ (2009)
- Bradford MM., "A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding", Analytical Biochem, 72(1-2), pp.248~254 (1976)
- Aebi H., "Catalase in vitro. In : Packer L, ed", Methods in Enzymol, 105, pp.121~126 (1984)
- Fridovich I., "Superoxide dismutase : an adaptation to a paramagnetic gas", J Biol Chem, 264(14), pp.7761~7764 (1989)
- Morin JE., "Characterization, kinetics and comparative properties of thiol : protein oxidoreductase", Archives Biochem Biophys, 189(2), pp.354~363 (1978)
- Stanton H., "ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro", Nature, 434(7033), pp.648~652 (2005)
- Endo Y., "A simultaneous estimation method of DNA and RNA by the orcinol reaction and a study on the reaction mechanism", J Biochem, 67(5), pp.629~633 (1970)
- Chowdhury R., "In vitro and in vivo reduction of sodium arsenite induced toxicity by aqueous garlic extract", Food Chem Toxicol, 46(2), pp.740~751 (2008)
- Bhattacharyya SS., "A synthetic coumarin (4-methyl-7 hydroxy coumarin) has anti-cancer potentials against DMBA-induced skin cancer in mice", Eur J Pharmacol, 614(1-3), pp.128~136 (2009)
- Kamaraj S., "Antioxidant and anticancer efficacy of hesperidin in benzo(a)pyrene induced lung carcinogenesis in mice", Invest New Drugs, 27(3), pp.214~222 (2009)
- Kamaraj S., "The effects of quercetin on antioxidant status and tumor markers in the lung and serum of mice treated with benzo(a)pyrene", Biol Pharm Bull, 30(12), pp.2268~2273 (2007)
- Li P., "Cytochrome c and dATP-dependent formation of Apaf-1", caspase-9 complex initiates an apoptotic protease cascade, 1997, pp.91(4), 479~489
- Wang ZQ., "PARP is important for genomic stability but dispensable in apoptosis", Genes Dev, 11(18), pp.2347~2358 (1997)