Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Stigmalactam from Orophea Enterocarpa Induces Human Cancer Cell Apoptosis Via a Mitochondrial Pathway

  • Banjerdpongchai, Ratana (Dept. of Biochemistry, Faculty of Medicine, Chiang Mai University) ;
  • Wudtiwai, Benjawan (Dept. of Biochemistry, Faculty of Medicine, Chiang Mai University) ;
  • Pompimon, Wilart (Laboratory of Natural Products, Center for Innovation in Chemistry, Faculty of Science, Lampang Rajabhat University)
  • Published : 2015.01.06
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Abstract

Stigmalactam, an aristolactam-type alkaloid extracted from Orophea enterocarpa, exerts cytotoxicity against several human and murine cancer cell lines, but the molecular mechanisms remain elusive. The aims of this study were to identify the mode and mechanisms of human cancer cell death induced by stigmalactam employing human hepatocellular carcinoma HepG2 and human invasive breast cancer MDA-MB-231 cells as models, compared to normal murine fibroblasts. It was found that stigmalactam was toxic to HepG2 and MDA-MB-231 cells with $IC_{50}$ levels of $23.0{\pm}2.67{\mu}M$ and $33.2{\pm}4.54{\mu}M$, respectively, using MTT assays. At the same time the $IC_{50}$ level towards murine normal fibroblast NIH3T3 cells was $24.4{\pm}6.75{\mu}M$. Reactive oxygen species (ROS) production was reduced in stigmalactam-treated cells dose dependently after 4 h of incubation, indicating antioxidant activity, measured by using 2',7',-dichlorohydrofluorescein diacetate and flow cytometry. Caspase-3 and caspase-9 activities were increased in a dose response manner, while stigmalactam decreased the mitochondrial transmembrane potential dose-dependently in HepG2 cells, using 3,3'-dihexyloxacarbocyanine iodide and flow cytometry, indicating mitochondrial pathway-mediated apoptosis. In conclusion, stigmalactam from O. enterocarpa was toxic to both HepG2 and MDA-MB-231 cells and induced human cancer HepG2 cells to undergo apoptosis via the intrinsic (mitochondrial) pathway.

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References

  1. Banjerdpongchai R, Khaw-On (2013). Terpinen-4-ol induces autophagic and apoptotic cell death in human leukemic HL-60 cells. Asian Pacific J Cancer Pre. 14, 7537-42. https://doi.org/10.7314/APJCP.2013.14.12.7537
  2. Banjerdpongchai R, Wilairat P (2005). Effects of water-soluble antioxidants and MAPKK/MEK inhibitor on curcumininduced apoptosis in HL-60 human leukemic cells. Asian Pacific J Cancer Prev, 6, 282-5.
  3. Banjerdpongchai R, Wudtiwai B, Sringarm K (2013). Cytotoxic and apoptotic-inducing effects of purple rice extracts and chemotherapeutic drugs on human cancer cell lines. Asian Pacific J Cancer Prev, 14, 6541-8. https://doi.org/10.7314/APJCP.2013.14.11.6541
  4. Chia YC, Chang FR, Teng CM, et al (2000). Aristolactams and dioxoaporphines from Fissistigma balansae and Fissistigma oldhamii. J Nat Prod. 63, 1160-3. https://doi.org/10.1021/np000063v
  5. Efferth T, Fu YJ, Zu YG, et al (2007). Molecular target-guided tumor therapy with natural products derived from traditional Chinese medicine. Current Med Chem. 14, 2024-32. https://doi.org/10.2174/092986707781368441
  6. Jain SK, Meena S, Gupta AP, et al (2014). Dysoxylum binectariferum bark as a new source of anticancer drug camptothecin: bioactivity-guided isolation and LCMS-based quantification. Bioorg Med Chem Lett. 24, 3146-9. https://doi.org/10.1016/j.bmcl.2014.05.001
  7. Lin CS, Chen PC, Wang CK, et al (2014). Antitumor Effects and Biological Mechanism of Action of the Aqueous Extract of the Camptotheca acuminata Fruit in Human Endometrial Carcinoma Cells. Evid Based Complement Alternat Med. 2014, 564810.
  8. Marques AM, Velozo LS, de Moreira DL, et al (2011). Aristolactams from roots of Ottonia anisum (Piperaceae). Nat Prod Commun. 6, 939-42.
  9. Nayyatip S, Thaichana P, Buayairaksa M, et al (2012). Aristolactam-type alkaloids from Orophea enterocarpa and their cytotoxicities. Int J Mol Sci. 13, 5010-8. https://doi.org/10.3390/ijms13045010
  10. Pang SQ, Wang GQ, Lin JS, et al (2014). Cytotoxic activity of the alkaloids from Broussonetia papyrifera fruits. Pharm Biol, 52, 1315-9. https://doi.org/10.3109/13880209.2014.891139
  11. Sun M, Zhang N, Wang X, et al (2014). Nitidine chloride induces apoptosis, cell cycle arrest, and synergistic cytotoxicity with doxorubicin in breast cancer cells. Tumour Biol. in press.
  12. Ulukan H, Swaan, PW (2002). Camptothecins: a review of their chemotherapeutic potential. Drugs. 62, 2039-57. https://doi.org/10.2165/00003495-200262140-00004
  13. Wudtiwai B, Sripanidkulchai B, Kongtawelert P, et al (2011). Methoxyflavone derivatives modulate the effect of TRAILinduced apoptosis in human leukemic cell lines. J Hematol Oncol. 4, 1-16. https://doi.org/10.1186/1756-8722-4-1

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