Antiproliferative Effects of Methanolic Extracts of Cryptocarya concinna Hance Roots on Oral Cancer Ca9-22 and CAL 27 Cell Lines Involving Apoptosis, ROS Induction, and Mitochondrial Depolarization

Cryptocarya-derived natural products were reported to have several biological effects such as the antiproliferation of some cancers. The possible antioral cancer effect of Cryptocarya-derived substances was little addressed as yet. In this study, we firstly used the methanolic extracts of C. concinna Hance roots (MECCrt) to evaluate its potential function in antioral cancer bioactivity. We found that MECCrt significantly reduced cell viability of two oral cancer Ca9-22 and CAL 27 cell lines in dose-responsive manners (P < 0.01). The percentages of sub-G1 phase and annexin V-positive of MECCrt-treated Ca9-22 and CAL 27 cell lines significantly accumulated (P < 0.01) in a dose-responsive manner as evidenced by flow cytometry. These apoptotic effects were associated with the findings that intracellular ROS generation was induced in MECCrt-treated Ca9-22 and CAL 27 cell lines in dose-responsive and time-dependent manners (P < 0.01). In a dose-responsive manner, MECCrt also significantly reduced the mitochondrial membrane potential in these two cell lines (P < 0.01–0.05). In conclusion, we demonstrated that MECCrt may have antiproliferative potential against oral cancer cells involving apoptosis, ROS generation, and mitochondria membrane depolarization.

[1]  T. Mak,et al.  Modulation of oxidative stress as an anticancer strategy , 2013, Nature Reviews Drug Discovery.

[2]  Mei-Yi Lin,et al.  Cortex Moutan Induces Bladder Cancer Cell Death via Apoptosis and Retards Tumor Growth in Mouse Bladders , 2013, Evidence-based complementary and alternative medicine : eCAM.

[3]  Zhuo-wei Hu,et al.  Antioxidant N-Acetylcysteine Attenuates Hepatocarcinogenesis by Inhibiting ROS/ER Stress in TLR2 Deficient Mouse , 2013, PloS one.

[4]  K. Awang,et al.  Antiplasmodial Alkaloids from the Bark of Cryptocarya nigra (Lauraceae) , 2013, Molecules.

[5]  Yu-Chao Chang,et al.  Selaginella tamariscina Attenuates Metastasis via Akt Pathways in Oral Cancer Cells , 2013, PloS one.

[6]  M. Hou,et al.  Marine algal natural products with anti-oxidative, anti-inflammatory, and anti-cancer properties , 2013, Cancer Cell International.

[7]  Hurng-Wern Huang,et al.  Golden Berry-Derived 4β-hydroxywithanolide E for Selectively Killing Oral Cancer Cells by Generating ROS, DNA Damage, and Apoptotic Pathways , 2013, PloS one.

[8]  M. Hou,et al.  Evaluating the performance of fibronectin 1 (FN1), integrin α4β1 (ITGA4), syndecan-2 (SDC2), and glycoprotein CD44 as the potential biomarkers of oral squamous cell carcinoma (OSCC) , 2013, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[9]  Hsueh-Wei Chang,et al.  Antiproliferative effects of goniothalamin on Ca9-22 oral cancer cells through apoptosis, DNA damage and ROS induction. , 2012, Mutation research.

[10]  Jen-Yang Tang,et al.  Antiproliferation and Induction of Apoptosis in Ca9-22 Oral Cancer Cells by Ethanolic Extract of Gracilaria tenuistipitata , 2012, Molecules.

[11]  Jen-Yang Tang,et al.  Anti-proliferative effect of methanolic extract of Gracilaria tenuistipitata on oral cancer cells involves apoptosis, DNA damage, and oxidative stress , 2012, BMC Complementary and Alternative Medicine.

[12]  K. Lee,et al.  Cytotoxic and Anti-HIV Phenanthroindolizidine Alkaloids from Cryptocarya chinensis† , 2012, Natural product communications.

[13]  D. Aizenbud,et al.  Green tea: a promising natural product in oral health. , 2012, Archives of oral biology.

[14]  Zhi-kai Guo,et al.  Anti-inflammatory flavonoids from Cryptocarya chingii. , 2012, Phytochemistry.

[15]  B. Canard,et al.  Alkylated flavanones from the bark of Cryptocarya chartacea as dengue virus NS5 polymerase inhibitors. , 2011, Journal of natural products.

[16]  I. Chen,et al.  New Flavanones from the Leaves of Cryptocarya chinensis and Their Antituberculosis Activity , 2011, Chemistry & biodiversity.

[17]  A. Kinghorn,et al.  The relevance of higher plants in lead compound discovery programs. , 2011, Journal of natural products.

[18]  Hsueh-Wei Chang,et al.  Goniothalamin inhibits growth of human lung cancer cells through DNA damage, apoptosis, and reduced migration ability. , 2011, Journal of agricultural and food chemistry.

[19]  Hsueh-Wei Chang,et al.  (-)-Anonaine induces DNA damage and inhibits growth and migration of human lung carcinoma h1299 cells. , 2011, Journal of agricultural and food chemistry.

[20]  V. Avery,et al.  7′,8′-Dihydroobolactone, a Trypanocidal α-Pyrone from the Rainforest Tree Cryptocarya obovata. , 2010 .

[21]  Shiow-Ju Lee,et al.  Cytotoxic flavonoids from the leaves of Cryptocarya chinensis. , 2010, Journal of Natural Products.

[22]  Y. Choi,et al.  Metabolomics: a tool for anticancer lead-finding from natural products. , 2010, Planta medica.

[23]  K. Kinoshita,et al.  Phenolic compounds from Cryptocarya konishii: their cytotoxic and tyrosine kinase inhibitory properties , 2010, Journal of Natural Medicines.

[24]  S. Fulda.  Evasion of Apoptosis as a Cellular Stress Response in Cancer , 2010, International journal of cell biology.

[25]  S. Teo,et al.  Systematic analysis of in vitro photo-cytotoxic activity in extracts from terrestrial plants in Peninsula Malaysia for photodynamic therapy. , 2009, Journal of photochemistry and photobiology. B, Biology.

[26]  Peng Huang,et al.  Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? , 2009, Nature Reviews Drug Discovery.

[27]  Hsueh-Wei Chang,et al.  Matrix metalloproteinases (MMP) 1 and MMP10 but not MMP12 are potential oral cancer markers , 2009, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[28]  Chunhua Han,et al.  Selective Induction of Apoptosis of Human Oral Cancer Cell Lines by Avocado Extracts Via a ROS-Mediated Mechanism , 2009, Nutrition and cancer.

[29]  Zvulun Elazar,et al.  ROS, mitochondria and the regulation of autophagy. , 2007, Trends in cell biology.

[30]  J. Nuzillard,et al.  Novel seco-dibenzopyrrocoline alkaloid from Cryptocarya oubatchensis. , 2006, Organic letters.

[31]  Seon-Hee Oh,et al.  A rapid and transient ROS generation by cadmium triggers apoptosis via caspase-dependent pathway in HepG2 cells and this is inhibited through N-acetylcysteine-mediated catalase upregulation. , 2006, Toxicology and applied pharmacology.

[32]  H. Takayama,et al.  Cytotoxic Chalcones and Flavanones from the Tree Bark of Cryptocarya costata , 2006, Zeitschrift für Naturforschung C - A Journal of Biosciences.

[33]  A. Samhan-Arias,et al.  Kaempferol blocks oxidative stress in cerebellar granule cells and reveals a key role for reactive oxygen species production at the plasma membrane in the commitment to apoptosis. , 2004, Free radical biology & medicine.

[34]  V. Dumontet,et al.  Cytotoxic Flavonoids and a-Pyrones from Cryptocarya o bovata , 2004 .

[35]  Jong-Ho Lee,et al.  Anti‐cancer effect of genistein in oral squamous cell carcinoma with respect to angiogenesis and in vitro invasion , 2003, Cancer science.

[36]  J. Masters.  False cell lines , 2002, International journal of cancer.

[37]  J. Masters.  False cell lines. , 2002, Carcinogenesis.

[38]  V. Dumontet,et al.  New cytotoxic flavonoids from Cryptocarya infectoria , 2001 .

[39]  H. Takayama,et al.  A new type of stilbene-related secondary metabolite, idenburgene, from Cryptocarya idenburgensis. , 2000, Chemical & pharmaceutical bulletin.

[40]  Massayoshi Yoshida,et al.  6-[ω-arylalkenyl]-5,6-dihydro-α-pyrones from Cryptocarya moschata (Lauraceae). , 2000 .

[41]  B. Evers,et al.  Mitochondrial DNA damage and altered membrane potential (ΔΨ) in pancreatic acinar cells induced by reactive oxygen species , 1999 .

[42]  Z. Elazar,et al.  Regulation of autophagy by ROS: physiology and pathology. , 2011, Trends in biochemical sciences.

[43]  N. Kyprianou,et al.  Apoptosis evasion: The role of survival pathways in prostate cancer progression and therapeutic resistance , 2006, Journal of cellular biochemistry.

[44]  M. Davies-Coleman,et al.  Naturally Occurring 6-Substituted 5,6-Dihydro-α-Pyrones , 1989 .

[45]  L. Jaenicke,et al.  Fortschritte der Chemie organischer Naturstoffe , 1939 .