Abstract
Grape seed proanthocyanidins are natural antioxidants which possess a broad spectrum of chemoprotective properties against free radicals and oxidative stress. In this study, we have assessed the cytotoxicity of a novel IH636 grape seed proanthocyanidin extract (GSPE) against MCF-7 human breast cancer cells, A-427 human lung cancer cells, CRL-1739 human gastric adenocarcinoma cells and K562 chronic myelogenous leukemic cells at 25 and 50 mg/lit concentrations for 0-72 h using cytomorphology and MTT cytotoxicity assay. In addition, we compared the effects on normal human gastric mucosal cells and normal J774A.1 murine macrophage cells with the effects on the cancer cell lines. Concentration- and time-dependent cytotoxic effects of GSPE were observed on the MCF-7 breast cancer, A-427 lung cancer and gastric adenocarcinoma cells. Following incubation of the MCF-7 cells with 25 mg/lit of the GSPE approximately 6.5, 30 and 43% inhibitions in cell growth were observed at 24, 48 and 72 h of incubation, respectively, while incubation of the MCF-7 cells with 50 mg/lit of the GSPE resulted in 11, 35 and 47% inhibition in cell growth at these same points, respectively. Similar results were observed in the A-427 and gastric adenocarcinoma cells. GSPE exhibited no cytotoxicity toward the neoplastic K562 myelogenous leukemic cells. However, GSPE enhanced the growth and viability of the normal human gastric mucosal cells and J774A.1 murine macrophage cells. These data demonstrate that GSPE exhibited cytotoxicity towards some cancer cells, while enhancing the growth and viability of the normal cells which were examined.
Similar content being viewed by others
References
CA Rice-Evans, L Packer (eds). Flavonoids in Health and Disease. Marcel Dekker, Inc., New York, 1997
E Candenas, L Packer (eds). Handbook of Antioxidants. Marcel Dekker, Inc., New York, 1996
Afanas'ev IB, Dorozhko AI, Brodskii AV, Kostyuk VA, Potapovitch AI: Chelating and free radical scavenging mechanisms of inhibitory action of rutin and quercetin in lipid peroxidation. Biochem Pharmacol 38: 1763–1769, 1989
Buening MK, Chang RL, Huang MT, Fortner JG, Wood AW, Conney AH: Activation and inhibition of benzo(a)pyrene and aflatoxin B1 metabolism in human liver microsomes by naturally occurring flavonoids. Cancer Res 41: 67–72, 1981
Kolodziej H, Haberland C, Woerdenbag HJ, Konings AWT: Moderate cytotoxicity of proanthocyanidins to human tumor cell lines. Phytother Res 9: 410–415, 1995
Bors W, Saran M: Radical scavenging by flavonoid antioxidants. Free Rad Res Commun 2: 289–294, 1987
Bagchi D, Garg A, Krohn RL, Bagchi M, Tran MX, Stohs SJ: Oxygen free radical scavenging abilities of vitamins C and E, and a grape seed proanthocyanidin extract in vitro. Res Commun Mol Pathol Pharmacol 95: 179–189, 1997
Bagchi D, Garg A, Krohn RL, Bagchi M, Bagchi DJ, Balmoori J, Stohs SJ: Protective effects of grape seed proanthocyanidins and selected antioxidants against TPA-induced hepatic and brain lipid peroxidation and DNA fragmentation, and peritoneal macrophage activation in mice. Gen Pharmacol 30: 771–776, 1998
Bagchi D, Kuszynski CA, Balmoori J, Bagchi M, Stohs SJ: Hydrogen peroxide-induced modulation of intracellular oxidized states in cultured macrophage J774A.1 and neuroactive PC-12 cells, and protection by a novel grape seed proanthocyanidin extract. Phytotherapy Res (in press)
Bagchi M, Balmoori J, Bagchi D, Kuszynski CA, Stohs SJ: Smokeless tobacco, oxidative stress, apoptosis and antioxidants in human oral keratinocytes. Free Rad Biol Med (in press)
Mosmann T: Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Meth 65: 55–63, 1983
Rao AK, Kuszynski CA, Benner E, Bishop MR, Jackson JD, Iversen PL, Joshi SS: Increased growth inhibition of human chronic myelogenous leukemic cells by a combination of c-myb antisense oligonucleotide and 4–hydroxyperoxycyclophosphamide in vitro. Inter J Oncol 11: 281–287, 1997
Chen ZY, Chan PT, Ho KY, Fung KP, Wang J: Antioxidative activity of natural flavonoids is governed by number and location of their aromatic hydroxyl groups. Chem Phys Lipids 79: 157–163, 1996
Hanefeld M, Herrmann K: On the occurrence of proanthocyanidins, leucoanthocyanidins and catechins in vegetables. Z Lebensm Unters Forsch 161: 243–248, 1976
Masquelier J, Michaud J, Laparra J, Dumon MC: Flavonoids and pycnogenols. Int J Vit Nutr Res 49: 307–311, 1979
Kashiwada Y, Nonaka G, Nishioka I, Lee KJ, Bori I, Fukushima Y, Bastow KF, Lee KH: Tannins as potent inhibitors of DNA topoisomerase II in vitro. J Pharm Sci 82: 487–492, 1993
Inokuchi J, Okabe H, Yamauchi T, Nagamatsu A, Nonaka G, Nishioka I: Antihypertensive substance in seeds of Areca catechu L. Life Sci 38: 1375–1382, 1986
Uchida S, Ikari N, Ohta H, Niwa M, Nonaka G, Nishioka I, Ozaki M: Inhibitory effects of condensed tannins on angiotensin converting enzyme. Jpn J Pharmacol 43: 242–246, 1987
Kakegawa H, Matsumoto H, Endo K, Satoh T, Nonaka G, Nishioka I: Inhibitory effects of tannins on hyaluronidase activation and on the degranulation from rat mesentary mast cells. Chem Pharm Bull 33: 5079–5082, 1985
Balde AM, Van Hoof L, Pieters LA, Vanden Berghe DA, Vlietinck AJ: Plant antiviral agents. VII. Antiviral and antibacterial proanthocyanidins from the bark of Pavetta owariensis. Phytother Res 4: 182–188, 1990
Kakiuchi N, Kusumoto IT, Hattori M, Namba T, Hatano T, Okuda T: Effects of condensed tannins and related compounds on reverse transcriptase. Phytother Res 5: 270–272, 1991
Nakashima H, Murakami T, Yamamoto N, Sakagami H, Tanuma S, Hatano T, Yoshida T, Okuda T: Inhibition of human immunodeficiency viral replication by tannins and related compounds. Antiviral Res 18: 91–103, 1992
Ezaki N, Kato M, Takizawa N, Morimoto S, Nonaka G, Nishioka I: Pharmacological studies on Linderae umbellatae Ramus, IV. Effects of condensed tannin related compounds on peptic activity and stressinduced gastric lesions in mice. Planta Med 51: 34–38, 1985
Sakagami H, Asano K, Tanuma S, Hatano T, Yoshida T, Okuda T: Stimulation of monocyte iodination and IL-1 production by tannins and related compounds. Anticancer Res 12: 377–388, 1992
Hikino H, Kiso Y, Hatano T, Yoshida T, Okuda T: Effects of the interaction of tannins with co-existing substances. V. Antihepatotoxic actions of tannins. J Ethnopharmacol 14: 19–29, 1985
Rice-Evans CA, Miller NJ, Paganda G: Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Rad Biol Med 20: 933–956, 1996
Salah N, Miller NJ, Paganga G, Tijburg L, Bolwell GP, Rice-Evans C: Polyphenolic flavonols as scavengers of aqueous phase radicals and as chain-breaking antioxidants. Arch Biochem Biophys 322: 339–346, 1995
Shahidi F, Wanasundara PKJ: Phenolic antioxidants. Crit Rev Food Sci Nutr 32: 67–103, 1992
Halliwell B: Oxidative stress, nutrition and health. Experimental strategies for optimization of nutritional antioxidant intake in humans. Free Rad Res 25: 57–74, 1996
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ye, X., Krohn, R., Liu, W. et al. The cytotoxic effects of a novel IH636 grape seed proanthocyanidin extract on cultured human cancer cells. Mol Cell Biochem 196, 99–108 (1999). https://doi.org/10.1023/A:1006926414683
Issue Date:
DOI: https://doi.org/10.1023/A:1006926414683