Anti-proliferative properties of commercial Pelargonium sidoides tincture, with cell-cycle G₀/G₁ arrest and apoptosis in Jurkat leukaemia cells

References

• Akhtar S, Meeran SM, Katiyar N, Katiyar SK. 2009. Grape seed proanthocyanidins inhibit the growth of human non-small cell lung cancer xenografts by targeting insulin-like growth factor binding protein-3, tumor cell proliferation, and angiogenic factors. Clin Cancer Res. 15:821–831.
   PubMed Web of Science ®Google Scholar
• Alexander A, Smith PF, Rosengren RJ. 2009. Cannabinoids in the treatment of cancer. Cancer Lett. 285:6–12.
   PubMed Web of Science ®Google Scholar
• Anilkumar M. 2010. Ethnomedicinal plants as anti-inflammatory and analgesic agents. In: Chattopadhyay D, editors. Ethnomedicine: a source of complementary therapeutics. Trivandrum: Research Signpost. p. 267–293.
   Google Scholar
• Azad N, Rojanasakul Y, Vallyathan V. 2008. Inflammation and lung cancer: roles of reactive oxygen/nitrogen species. J Toxicol Environ Health B Crit Rev. 11:1–15.
   PubMed Web of Science ®Google Scholar
• Balunas MJ, Kinghorn AD. 2005. Drug discovery from medicinal plants. Life Sci. 78:431–441.
   PubMed Web of Science ®Google Scholar
• Barron D, Varin L, Ibrahim RK, Harborne JB, Williams CA. 1988. Sulphated flavonoids – an update. Phytochemistry 27:2375–2395.
   Web of Science ®Google Scholar
• Bezerra DP, Militão GCG, De Castro FO, Pessoa C, de Moraes MO, Silveira ER, Lima MA, Elmiro FJ, Costa-Lotufo LV. 2007. Piplartine induces inhibition of leukemia cell proliferation triggering both apoptosis and necrosis pathways. Toxicol In Vitro 21:1–8.
   PubMed Web of Science ®Google Scholar
• Boyd MR, Paull KD. 1995. Some practical considerations and applications of the National Cancer Institute in vitro anticancer drug discovery screen. Drug Dev Res. 34:91–109.
   Web of Science ®Google Scholar
• Brendler T, Van Wyk B. 2008. A historical, scientific and commercial perspective on the medicinal use of Pelargonium sidoides (Geraniaceae). J Ethnopharmacol. 119:420–433.
   PubMed Web of Science ®Google Scholar
• Brown NS, Bicknell R. 2001. Hypoxia and oxidative stress in breast cancer. Oxidative stress: its effects on the growth, metastatic potential and response to therapy of breast cancer. Breast Cancer Res. 3:323–327.
   PubMed Web of Science ®Google Scholar
• Callemien D, Collin S. 2008. Use of RP-HPLC-ESI (−)-MS/MS to differentiate various proanthocyanidin isomers in lager beer extracts. J Am Soc Brew Chem. 66:109–115.
   Web of Science ®Google Scholar
• Chu C, Tsai Y, Wang C, Lin W, Tseng T. 2001. Induction of apoptosis by esculetin in human leukemia cells. Eur J Pharmacol. 416:25–32.
   PubMed Web of Science ®Google Scholar
• Chung M, Lai M, Yen M, Wu R, Lin C. 1997. Phenolics from Hypericum geminiflorum. Phytochemistry 44:943–947.
   Web of Science ®Google Scholar
• Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. 2009. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 30:1073–1081.
   PubMed Web of Science ®Google Scholar
• Cragg GM, Newman DJ. 2005. Plants as a source of anti-cancer agents. J Ethnopharmacol. 100:72–79.
   PubMed Web of Science ®Google Scholar
• Dajas F. 2012. Life or death: neuroprotective and anticancer effects of quercetin. J Ethnopharmacol. 143:383–396.
   PubMed Web of Science ®Google Scholar
• Del Follo-Martinez A, Banerjee N, Li X, Safe S, Mertens-Talcott S. 2013. Resveratrol and quercetin in combination have anticancer activity in colon cancer cells and repress oncogenic microRNA-27a. Nutr Cancer 65:494–504.
   PubMed Web of Science ®Google Scholar
• Federico A, Morgillo F, Tuccillo C, Ciardiello F, Loguercio C. 2007. Chronic inflammation and oxidative stress in human carcinogenesis. Int J Cancer 121:2381–2386.
   PubMed Web of Science ®Google Scholar
• Fuertes MA, Castilla J, Alonso C, Pérez JM. 2003. Cisplatin biochemical mechanism of action: from cytotoxicity to induction of cell death through interconnections between apoptotic and necrotic pathways. Curr Med Chem. 10:257–266.
   PubMed Web of Science ®Google Scholar
• Fujiki H, Sueoka E, Watanabe T, Suganuma M. 2014. Synergistic enhancement of anticancer effects on numerous human cancer cell lines treated with the combination of EGCg, other green tea catechins, and anticancer compounds. J Cancer Res Clin Oncol. 140:1–12.
   PubMed Web of Science ®Google Scholar
• Gödecke T, Kaloga M, Kolodziej H. 2005. A phenol glucoside, uncommon coumarins and flavonoids from Pelargonium sidoides DC. Z Naturforsch B. 60:677–682.
   Google Scholar
• Goel A, Jhurani S, Aggarwal BB. 2008. Multi-targeted therapy by curcumin: how spicy is it? Mol Nutr Food Res. 52:1010–1030.
   PubMed Web of Science ®Google Scholar
• Grivennikov SI, Greten FR, Karin M. (2010). Immunity, inflammation, and cancer. Cell 140:883–899.
   PubMed Web of Science ®Google Scholar
• Hauer H, Germer S, Elsäßer J, Ritter T. 2010. Benzopyranones and their sulfate esters from Pelargonium sidoides. Planta Med. 76:350–352.
   PubMed Web of Science ®Google Scholar
• Hsieh C, Hernández-Ledesma BBO. 2011. Cell proliferation inhibitory and apoptosis-inducing properties of anacardic acid and lunasin in human breast cancer MDA-MB-231 cells. Food Chem. 125:630–636.
   Web of Science ®Google Scholar
• Huang P, Hseu Y, Lee M, Kumar KJS, Wu C, Hsu L, Liao J, Cheng I, Kuo Y, Huang S. 2012. In vitro and in vivo activity of gallic acid and Toona sinensis leaf extracts against HL-60 human premyelocytic leukemia. Food Chem Toxicol Toxicol. 50:3489–3497.
   PubMed Web of Science ®Google Scholar
• Itharat A, Houghton PJ, Eno-Amooquaye E, Burke PJ, Sampson JH, Raman A. 2004. In vitro cytotoxic activity of Thai medicinal plants used traditionally to treat cancer. J Ethnopharmacol. 90:33–38.
   PubMed Web of Science ®Google Scholar
• Ji B, Hsu W, Yang J, Hsia T, Lu C, Chiang J, Yang J, Lin C, Lin J, Suen LW. 2009. Gallic acid induces apoptosis via caspase-3 and mitochondrion-dependent pathways in vitro and suppresses lung xenograft tumor growth in vivo. J Agric Food Chem. 57:7596–7604.
   PubMed Web of Science ®Google Scholar
• Johnson JJ, Petiwala SM, Syed DN, Rasmussen JT, Adhami VM, Siddiqui IA, Kohl AM, Mukhtar H. 2012. α-Mangostin, a xanthone from mangosteen fruit, promotes cell cycle arrest in prostate cancer and decreases xenograft tumor growth. Carcinogenesis 33:413–419.
   PubMed Web of Science ®Google Scholar
• Kaur M, Mandair R, Agarwal R, Agarwal C. 2008. Grape seed extract induces cell cycle arrest and apoptosis in human colon carcinoma cells. Nutr Cancer 60:2–11.
   PubMed Web of Science ®Google Scholar
• Kaur M, Kohli S, Sandhu S, Bansal Y, Bansal G. 2015. Coumarin: a promising scaffold for anticancer agents. Anticancer Agents Med Chem. 15:1032–1048.
   PubMed Web of Science ®Google Scholar
• Kayser O, Kolodziej H. 1995. Highly oxygenated coumarins from Pelargonium sidoides. Phytochemistry 39:1181–1185.
   Web of Science ®Google Scholar
• Khan N, Mukhtar H. 2008. Multitargeted therapy of cancer by green tea polyphenols. Cancer Lett. 269:269–280.
   PubMed Web of Science ®Google Scholar
• Kim H, Lee E, Kim J, Jung B, Chong Y, Ahn J, Lim Y. 2008. A flavonoid gossypin binds to cyclin-dependent kinase 2. Bioorg Med Chem Lett. 18:661–664.
   PubMed Web of Science ®Google Scholar
• Kim C, Griffiths W, Taylor P. 2009. Components derived from Pelargonium stimulate macrophage killing of Mycobacterium species. J Appl Microbiol. 106:1184–1193.
   PubMed Web of Science ®Google Scholar
• Kok S, Yeh C, Chen M, Kuo MY. 2009. Esculetin enhances TRAIL-induced apoptosis through DR5 upregulation in human oral cancer SAS cells. Oral Oncol. 45:1067–1072.
   PubMed Web of Science ®Google Scholar
• Kolodziej H. 2007. Fascinating metabolic pools of Pelargonium sidoides and Pelargonium reniforme, traditional and phytomedicinal sources of the herbal medicine Umckaloabo®. Phytomedicine 14:9–17.
   PubMedGoogle Scholar
• Kong JH, Kim YB, Yoon CW, Cha YJ, Han SS, Rhee CK, Oak M. 2009. Pelargonium sidoides syrup. World Intellectual Property Organisation, WO/2009/011498.
   Google Scholar
• Kundu JK, Surh Y. 2012. Emerging avenues linking inflammation and cancer. Free Radic Biol Med. 52:2013–2037.
   PubMed Web of Science ®Google Scholar
• Latté KP, Kayser O, Tan N, Kaloga M, Kolodziej H. 2000. Unusual coumarin patterns of Pelargonium species forming the origin of the traditional herbal medicine umckaloabo. Z Naturforschung C 55:528–533.
   Web of Science ®Google Scholar
• Lee S, Cekanova M, Baek SJ. 2008. Multiple mechanisms are involved in 6-gingerol-induced cell growth arrest and apoptosis in human colorectal cancer cells. Mol Carcinog. 47:197–208.
   PubMed Web of Science ®Google Scholar
• Lemmich J, Shabana M. 1984. Coumarin sulphates of Seseli libanotis. Phytochemistry 23:863–865.
   Web of Science ®Google Scholar
• Li H, Yashiki S, Sonoda J, Lou H, Ghosh SK, Byrnes JJ, Lema C, Fujiyoshi T, Karasuyama M, Sonoda S. 2000. Green tea polyphenols induce apoptosis in vitro in peripheral blood T lymphocytes of adult T-cell leukemia patients. Cancer Sci. 91:34–40.
   Google Scholar
• Lucia MS, Torkko KC. 2004. Inflammation as a target for prostate cancer chemoprevention: pathological and laboratory rationale. J Urol. 171:S30–S35.
   Google Scholar
• Madlener S, Illmer C, Horvath Z, Saiko P, Losert A, Herbacek I, Grusch M, Elford HL, Krupitza G, Bernhaus A. 2007. Gallic acid inhibits ribonucleotide reductase and cyclooxygenases in human HL-60 promyelocytic leukemia cells. Cancer Lett. 245:156–162.
   PubMed Web of Science ®Google Scholar
• Mantena SK, Baliga MS, Katiyar SK. 2006. Grape seed proanthocyanidins induce apoptosis and inhibit metastasis of highly metastatic breast carcinoma cells. Carcinogenesis 27:1682–1691.
   PubMed Web of Science ®Google Scholar
• Matthys H, Kamin W, Funk P, Heger M. 2007. Pelargonium sidoides preparation (EPs® 7630) in the treatment of acute bronchitis in adults and children. Phytomedicine 14:69–73.
   PubMedGoogle Scholar
• Medina S, Domínguez-Perles R, García-Viguera C, Cejuela-Anta R, Martínez-Sanz JM, Ferreres F, Gil-Izquierdo A. 2012. Physical activity increases the bioavailability of flavanones after dietary aronia-citrus juice intake in triathletes. Food Chem. 135:2133–2137.
   PubMed Web of Science ®Google Scholar
• Meeran SM, Katiyar SK. 2007. Grape seed proanthocyanidins promote apoptosis in human epidermoid carcinoma A431 cells through alterations in Cdki-Cdk-cyclin cascade, and caspase-3 activation via loss of mitochondrial membrane potential. Exp Dermatol. 16:405–415.
   PubMed Web of Science ®Google Scholar
• Mizutani H, Tada-Oikawa S, Hiraku Y, Kojima M, Kawanishi S. 2005. Mechanism of apoptosis induced by doxorubicin through the generation of hydrogen peroxide. Life Sci. 76:1439–1453.
   PubMed Web of Science ®Google Scholar
• Moyo M, Aremu AO, Gruz J, S˘ubrtová M, Szüc˘ová L, Dolez˘al K, Van Staden J. 2013. Conservation strategy for Pelargonium sidoides DC: phenolic profile and pharmacological activity of acclimatized plants derived from tissue culture. J Ethnopharmacol. 149:557–561.
   PubMed Web of Science ®Google Scholar
• Nakagawa Y, Iinuma M, Naoe T, Nozawa Y, Akao Y. 2007. Characterized mechanism of alpha-mangostin-induced cell death: caspase-independent apoptosis with release of endonuclease-G from mitochondria and increased miR-143 expression in human colorectal cancer DLD-1 cells. Bioorg Med Chem. 15:5620–5628.
   PubMed Web of Science ®Google Scholar
• Nandakumar V, Singh T, Katiyar SK. 2008. Multi-targeted prevention and therapy of cancer by proanthocyanidins. Cancer Lett. 269:378–387.
   PubMed Web of Science ®Google Scholar
• Owa T, Yoshino H, Yoshimatsu K, Nagasu T. 2001. Cell cycle regulation in the G1 phase: a promising target for the development of new chemotherapeutic anticancer agents. Curr Med Chem. 8:1487–1503.
   PubMed Web of Science ®Google Scholar
• Pèrez JM, Kelland LR, Montero EI, Boxall FE, Fuertes MA, Alonso C, Navarro-Ranninger C. 2003. Antitumor and cellular pharmacological properties of a novel platinum (IV) complex: trans-[PtCl2(OH)2(dimethylamine)(isopropylamine)]. Mol Pharmacol. 63:933–944.
   PubMed Web of Science ®Google Scholar
• Phillips MM, Case RJ, Rimmer CA, Sander LC, Sharpless KE, Wise SA, Yen JH. 2010. Determination of organic acids in Vaccinium berry standard reference materials. Anal Bioanal Chem. 398:425–434.
   PubMed Web of Science ®Google Scholar
• Pinedo HM, Peters GF. 1988. Fluorouracil: biochemistry and pharmacology. J Clin Oncol. 6:1653–1664.
   PubMed Web of Science ®Google Scholar
• Ramasamy K, Agarwal R. 2008. Multitargeted therapy of cancer by silymarin. Cancer Lett. 269:352–362.
   PubMed Web of Science ®Google Scholar
• Riveiro ME, Moglioni A, Vazquez R, Gomez N, Facorro G, Piehl L, de Celis ER, Shayo C, Davio C. 2008. Structural insights into hydroxycoumarin-induced apoptosis in U-937 cells. Bioorg Med Chem. 16:2665–2675.
   PubMed Web of Science ®Google Scholar
• Saba NF, Haigentz M, Vermorken JB, Strojan P, Bossi P, Rinaldo A, Takes RP, Ferlito A. 2015. Prevention of head and neck squamous cell carcinoma: removing the “chemo” from ”chemoprevention”. Oral Oncol. 51:112–118.
   PubMed Web of Science ®Google Scholar
• Sang S, Hong J, Wu H, Liu J, Yang CS, Pan M, Badmaev V, Ho C. 2009. Increased growth inhibitory effects on human cancer cells and anti-inflammatory potency of shogaols from Zingiber officinale relative to gingerols. J Agric Food Chem. 57:10645–10650.
   PubMed Web of Science ®Google Scholar
• Schötz K, Nöldner M. 2007. Mass spectroscopic characterisation of oligomeric proanthocyanidins derived from an extract of Pelargonium sidoides roots (EPs® 7630) and pharmacological screening in CNS models. Phytomedicine 14:32–39.
   PubMed Web of Science ®Google Scholar
• Schulze-Bergkamen H, Krammer PH. 2004. Apoptosis in cancer-implications for therapy. Semin Oncol. 31:90–119.
   PubMed Web of Science ®Google Scholar
• Seeram NP, Adams LS, Zhang Y, Lee R, Sand D, Scheuller HS, Heber D. 2006. Blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts inhibit growth and stimulate apoptosis of human cancer cells in vitro. J Agric Food Chem. 54:9329–9339.
   PubMed Web of Science ®Google Scholar
• Sharma G, Tyagi AK, Singh RP, Chan DCF, Agarwal R, Chan DCF, Agarwal R. 2004. Synergistic anti-cancer effects of grape seed extract and conventional cytotoxic agent doxorubicin against human breast carcinoma cells. Breast Cancer Res Treat. 85:1–12.
   PubMed Web of Science ®Google Scholar
• Shi L, Chen J, Wang Y, Sun G, Liu J, Zhang J, Yan W, Qian C, Liu N, Fu Z. 2012. Gossypin induces G2/M arrest in human malignant glioma U251 cells by the activation of Chk1/Cdc25C pathway. Cell Mol Neurobiol. 32:289–296.
   PubMed Web of Science ®Google Scholar
• Steenkamp V, Gouws M. 2006. Cytotoxicity of six South African medicinal plant extracts used in the treatment of cancer. S Afr J Botany 72:630–633.
   Web of Science ®Google Scholar
• Stewart ZA, Westfall MD, Pietenpol JA. 2003. Cell-cycle dysregulation and anticancer therapy. Trends Pharmacol Sci. 24:139–145.
   PubMed Web of Science ®Google Scholar
• Sudjaroen Y, Haubner R, Würtele G, Hull WE, Erben G, Spiegelhalder B, Changbumrungv S, Bartsch H, Owen RW. 2005. Isolation and structure elucidation of phenolic antioxidants from Tamarind (Tamarindus indica L.) seeds and pericarp. Food Chem Toxicol. 43:1673–1682.
   PubMed Web of Science ®Google Scholar
• Sun Y, Jiang X, Chen S, Price BD. 2006. Inhibition of histone acetyltransferase activity by anacardic acid sensitizes tumor cells to ionizing radiation. FEBS Lett. 580:4353–4356.
   PubMed Web of Science ®Google Scholar
• Takimoto CH. 2003. Anticancer drug development at the US National Cancer Institute. Cancer. Chemother Pharmacol. 52:29–33.
   Web of Science ®Google Scholar
• Verma S, Singh A, Mishra A. 2013. Gallic acid: molecular rival of cancer. Environ Toxicol Pharmacol. 35:473–485.
   PubMed Web of Science ®Google Scholar
• Wang C, Hsieh Y, Chu C, Lin Y, Tseng T. 2002. Inhibition of cell cycle progression in human leukemia HL-60 cells by esculetin. Cancer Lett. 183:163–168.
   PubMed Web of Science ®Google Scholar
• Wen-Sheng Y, Li H, Xin-Min C, Yang L. 1992. Two afzelechin glycosides from Arthromeris mairei. Phytochemistry 31:4385–4386.
   Web of Science ®Google Scholar
• Yang GY, Liao J, Kim K, Yurkow EJ, Yang CS. 1998. Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols. Carcinogenesis 19:611–616.
   PubMed Web of Science ®Google Scholar
• You BR, Moon HJ, Han YH, Park WH. 2010. Gallic acid inhibits the growth of HeLa cervical cancer cells via apoptosis and/or necrosis. Food Chem Toxicol. 48:1334–1340.
   PubMed Web of Science ®Google Scholar