Browse > Article
http://dx.doi.org/10.7314/APJCP.2014.15.15.6075

Distinct Pro-Apoptotic Properties of Zhejiang Saffron against Human Lung Cancer Via a Caspase-8-9-3 Cascade  

Liu, Dan-Dan (Department of Basic Medicine, Zhejiang Medical College)
Ye, Yi-Lu (Department of Basic Medicine, Zhejiang Medical College)
Zhang, Jing (Department of Basic Medicine, Zhejiang Medical College)
Xu, Jia-Ni (Department of Basic Medicine, Zhejiang Medical College)
Qian, Xiao-Dong (Department of Pharmacy, Huzhou Central Hospital)
Zhang, Qi (Department of Basic Medicine, Zhejiang Medical College)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.15, 2014 , pp. 6075-6080 More about this Journal
Abstract
Lung cancer is the leading cause of cancer-related death worldwide. Here we investigated the antitumor effect and mechanism of Zhejiang (Huzhou and Jiande) saffron against lung cancer cell lines, A549 and H446. Using high performance liquid chromatography (HPLC), the contents of crocin I and II were determined. In vitro, MTT assay and annexin-V FITC/PI staining showed cell proliferation activity and apoptosis to be changed in a dose- and time-dependent manner. The inhibition effect of Jiande saffron was the strongest. In vivo, when mice were orally administered saffron extracts at dose of 100mg/kg/d for 28 days, xenograft tumor size was reduced, and ELISA and Western blotting analysis of caspase-3, -8 and -9 exhibited stronger expression and activity than in the control. In summary, saffron from Zhejiang has significant antitumor effects in vitro and in vivo through caspase-8-caspase-9-caspase-3 mediated cell apoptosis. It thus appears to have more potential as a therapeutic agent.
Keywords
Saffron extract; A549 cell; H446 cell; pro-apoptotic; caspase;
Citations & Related Records
Times Cited By KSCI : 3  (Citation Analysis)
연도 인용수 순위
1 Ashrafi M, Bathaie SZ, Taghikhani M, et al (2005). The effect of carotenoids obtained from saffron on histone H1 structure and H1-DNA interaction. Int J Bio Macromol, 36, 246-52.   DOI
2 Bakshi H, Sam S, Feroz A, et al (2009). Crocin from Kashmiri saffron (Crocus sativus) induces in vitro and in vivo xenograft growth inhibition of Dalton's lymphoma (DLA) in mice. Asian Pac J Cancer Prev, 10, 887-90.
3 Bakshi H, Sam S, Rozati R, et al (2010). DNA fragmentation and cell cycle arrest: a hallmark of apoptosis induced by crocin from kashmiri saffron in a human pancreatic cancer cell line. Asian Pac J Cancer Prev, 11, 675-9.
4 Chen J, Han H, Chen M, et al (2014). Inactivated Sendai Virus strain Tianjin induces apoptosis in human breast cancer MDA-MB-231 cells. Asian Pac J Cancer Prev, 15, 5023-8.   과학기술학회마을   DOI
5 Coate LE, Shepherd FA (2010). Maintenance therapy in advanced non-small cell lung cancer. J Thorac Oncol, 5, 723-34.
6 Dhar A, Mehta S, Dhar G, et al (2009). Crocetin inhibits pancreatic cancer cell proliferation and tumor progression in a xenograft mouse model. Mol Cancer Ther, 8, 315-23.   DOI
7 Dziegiel P, Dumanska M, Forgacz J, et al (2004). Intensity of apoptosis as related to the expression of metallothionein (MT), caspase-3 (cas-3) and Ki-67 antigen and the survival time of patients with primary colorectal adenocarcinomas. Rocz Akad Med Bialymst, 49, 5-7.
8 Jiang H, Zhang L, Liu J, et al (2012). Knockdown of zinc finger protein X-linked inhibits prostate cancer cell proliferation and induces apoptosis by activating caspase-3 and caspase-9. Cancer Gene Ther, 19, 684-9.   DOI
9 Giaccio M (2004). Crocetin from saffron: an active component of an ancient spice. Crit Rev Food Sci Nutr, 44, 155-72.   DOI
10 Grimaudo S, Meli M, Di Cristina A, et al (2013). The new iodoacetamidobenzofuran derivative TR120 decreases STAT5 expression and induces antitumor effects in imatinibsensitive and imatinib-resistant BCR-ABL-expressing leukemia cells. Anticancer Drugs, 24, 384-33.   DOI
11 Joukar S, Najafipour H, Khaksari M, et al (2010). The effect of saffron consumption on biochemical and histopathological heart indices of rats with myocardial infarction. Cardiovasc Toxicol, 10, 66-71.   DOI   ScienceOn
12 Li CY, Huang WF, Wang QL, et al (2012). Crocetin induces cytotoxicity in colon cancer cells via p53-independent mechanisms. Asian Pac J Cancer Prev, 13, 3757-61.   과학기술학회마을   DOI
13 Samarghandian S, Tavakkol Afshari J, Davoodi S (2011). Suppression of pulmonary tumor promotion and induction of apoptosis by Crocus sativus L. extraction. Appl Biochem Biotechnol, 164, 238-47.   DOI
14 Magesh V, Singh JP, Selvendiran K, et al (2006). Antitumour activity of crocetin in accordance to tumor incidence, antioxidant status, drug metabolizing enzymes and histopathological studies. Mol Cell Bioch, 287, 127-35.   DOI
15 Rezaee R, Hosseinzadeh H (2013). Safranal: from an aromatic natural product to a rewarding pharmacological agent. Iran J Basic Med Sci, 16, 12-26.
16 Samarghandian S, Boskabady MH, Davoodi S (2010). Use of in vitro assays to assess the potential antiproliferative and cytotoxic effects of saffron (Crocus sativus L.) in human lung cancer cell line. Pharmacogn Mag, 6, 309-14.   DOI
17 Schmidt M, Betti G, Hensel A (2007). Saffron in phytotherapy: pharmacology and clinical uses. Wien Med Wochenschr, 157, 315-19.   DOI
18 Sun J, Xu XM, Ni CZ, et al (2011). Crocin inhibits proliferation and nucleic acid synthesis and induces apoptosis in the human tongue squamous cell carcinoma cell line Tca8113. Asian Pac J Cancer Prev, 12, 2679-83.
19 Sun Y, Xu HJ, Zhao YX, et al (2013). Crocin exhibits antitumor effects on human leukemia HL-60 cells in vitro and in vivo. Evid Based Complement Alternat Med, 2013, 690164.
20 Tavakkol AJ, Brook A, Mousavi SH (2008). Study of cytotoxic and apoptogenic properties of saffron extract in human cancer cell lines. Food Chem Toxic, 46, 3443-7.   DOI   ScienceOn
21 Zhang Z, Wang CZ, Wen XD, et al (2013). Role of saffron and its constituents on cancer chemoprevention. Pharm Biol, 51, 920-4.   DOI
22 Shepherd FA, Douillard JY, Blumenschein GR (2011). Immunotherapy for non-small cell lung cancer novel approaches to improve patient outcome. J Thorac Oncol, 6, 1763-73.   DOI   ScienceOn
23 Zou X, Liu SL, Zhou JY, et al (2012). Beta-asarone induces LoVo colon cancer cell apoptosis by up-regulation of caspases through a mitochondrial pathway in vitro and in vivo. Asian Pac J Cancer Prev, 13, 5291-8.   과학기술학회마을   DOI   ScienceOn
24 Hoshyar R, Bathaie SZ, Sadeghizadeh M (2013). Crocin triggers the apoptosis through increasing the Bax/Bcl-2 ratio and caspase activation in human gastric adenocarcinoma AGS cells. DNA Cell Biol, 32, 50-7.   DOI