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Anticancer Effects of Taiwanofungus Camphoratus Extracts, Isolated Compounds and Its Combinational Use

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Anticancer Effects of Taiwanofungus Camphoratus Extracts, Isolated Compounds and Its Combinational Use J Exp Clin Med 2010;2(6):274e281 Contents lists available at ScienceDirect Journal of Experimental and Clinical Medicine journal homepage: http://www.jecm-online.com REVIEW ARTICLE Anticancer Effects of Taiwanofungus camphoratus Extracts, Isolated Compounds and its Combinational use Ying-Chen Chen 1, Hsio-O Ho 1, Chin-Hua Su 2, Ming-Thau Sheu 1,3,* 1 School of Pharmacy, College of Pharmacy, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan 2 School of Medicine, College of Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan 3 Clinical Research Center and Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan article info Taiwanofungus camphoratus is an indigenous mushroom in Taiwan, which has been used as a traditional Article history: medicine to treat many health-related problems. Several biological activities have been reported on Received: Jun 23, 2010 T. camphoratus ranging from anti-inflammatory antihypertension to anticancer and so on. Cancer is Revised: Aug 1, 2010 a major cause of death in Taiwan, and unfortunately, there is no satisfied treatment presently. Thus, Accepted: Aug 31, 2010 a review article about the anticancer effect of T. camphoratus would be a great importance. This article Available online 20 October 2010 reviews anticancer activities being performed with crude extracts and isolated compounds from T. camphoratus and their synergistic effects. The source of T. camphoratus might be from its fruiting KEY WORDS: bodies, mycelia, and fermented culture broth and be extracted from water, methanol, ethanol, ethyl anticancer; acetate, or chloroform, which showed versatile anticancer activities. In addition, various compounds combination; have been further purified from these extracts, such as terpenoids, maleic and succinic acids derivatives, crude extracts; polysaccharides, and other compounds, and they also showed potent cytotoxicity. Besides, T. camphoratus pure compounds; Taiwanofungus camphoratus not only has cytotoxic effect but also produces synergistic anticancer effect with trichostatin A, lova- statin, and taxol. It is concluded that T. camphoratus could be considered as a potential anticancer agent to make cancer no longer a frightening nightmare. However, clinical trials of T. camphoratus on human subjects are absent, and the involved mechanism remains unclear. Hence, further investigations would be required. Copyright Ó 2010, Taipei Medical University. Published by Elsevier Taiwan LLC. All rights reserved. 1. Introduction spores. However, according to the morphology of the fruiting body, the name Antrodia camphorata was proposed. In 2004, a phylogenetic Taiwanofungus camphoratus (T. camphoratus), an orange to brown- analysis indicated that the ribosomal RNA of A. camphorata.isfar red colored fungus, parasitizes only in the inner cavity of an endemic related to other Antrodia species, and the fungus was designated the and endangered host, Cinnamomum kanehirai Hay (Lauraceae) (Bull new name, T. camphoratus.3 InTaiwan, it has beenwell known as “niu- camphor tree), which distributes at an altitude of 200e2000 m in chang-chih,”“chang-chih,”“niu-chang-ku,” or “chang-ku.” the mountains of Taoyuan, Miaoli, Nantou, Kaohsiung, Taitung, and Being an indigenous species, T. camphoratus was traditionally Hualien in Taiwan. T. camphoratus is a very scarce and an expensive used by Taiwan aborigines to treat food and drug intoxication, mushroom because it grows extremely slow only from June to diarrhea, abdominal pain, hypertension, skin itching, and improve October and is difficult to be cultivated in the greenhouse.1,2 the immune system and liver function.2 This medicinal mushroom T. camphoratus belongs to the following taxonomy: Kingdom: has been believed to improve health and increase longevity, and Mycoteae; Division: Amastigomycota; Subdivision: Basidiomytina; long been regarded as health foods. Several biological activities e Class: Hymenomycetes; Order: Aphyllophorales; Family: Poly- have been reported for T. camphoratus, such as anticancer,5 7 e poraceae; Genus: Taiwanofungus; Species: camphorautus.3 antihepatotoxic,8,9 antihypertensive,10,11 anti-inflammatory,12 15 This unique Formosan mushroom was initially reported as Gano- antioxidant,16,17 and neuroprotective18 activities. derma camphoratum by Zang and Su4 in 1990 because of a careless Cancer has been the leading health killer in Taiwan since 1982. misidentification from the contaminated specimen of Ganoderma In 2008, 38,913 people died of malignant tumor, which accounts for 27.3% death, and it means every 13.5 minutes, there was one case of death because of cancer. It did bring about lots of tragedies, and moreover, the incidence of cancer continues to increase so far. * Corresponding author. School of Pharmacy, College of Pharmacy, No. 250, Therefore, many researchers devote themselves to the study of Wu-Hsing Street, Taipei 110, Taiwan. E-mail: [email protected] (M.-T. Sheu). mechanism, treatment, and prevention in oncology. Unfortunately, 1878-3317/$ e see front matter Copyright Ó 2010, Taipei Medical University. Published by Elsevier Taiwan LLC. All rights reserved. doi:10.1016/j.jecm.2010.08.003 Anticancer effects of Taiwanofungus camphoratus 275 various cytotoxic chemotherapeutic agents, such as paclitaxel, filtered with filter paper while the residue was further extracted doxorubicin, and other widely used anticancer drugs currently, lack under the same condition twice. The filtrates collected from three the specificity to only kill tumor cells without simultaneously separate extractions were combined and evaporated to dryness damaging the healthy tissues and thus causing severe side effects. under vacuum. Concentrated methanol extract was partitioned In order to solve the problems of dose-limiting toxicity associated between water and ethyl acetate (1:3, v/v) three times to give an with chemotherapeutic agents and drug resistance, development of ethyl acetate extract, which was then evaporated to dryness under cancer chemopreventive agents and improvement of cancer treat- vacuum. The ethyl acetate extract decreased the cell growth of ment are very important and urgent. The aim of this article was to human hepatoma cancer cell line (Hep G2) and PLC/PRF/5 cells in review the literatures mentioning the method of extraction or a dose-dependent manner. In Fas/APO-1 positive-Hep G2 cells, the isolation and anticancer effect of various extracts, isolated extract ascended the expression level of Fas/APO-1 and its two compounds, and their combinational use of T. camphoratus. forms of ligands, membrane-bound Fas ligand, and soluble Fas ligand with a p53-independent manner. Ethyl acetate extract also 2. Anticancer Activities of Extracts initiated mitochondrial apoptotic pathway through regulation of Bcl-2 family proteins expression, release of cytochrome c, and T. camphoratus has been used for a long time, and its pharmaco- activation of caspase-9 in Hep G2 and PLC/PRF/5 cells as well. logical effects have been investigated by many scientific researches. Moreover, it suppressed the cell survival signaling by strengthening This part of review emphasizes the anticancer effects of crude the amount of IkBa in cytoplasm and decreasing the level and extracts of T. camphoratus, and they are tabulated in Table 1. activity of nuclear factor kB (NF-kB) in the nucleus and then attenuated the expression of Bcl-XL in Hep G2 and PLC/PRF/5 cells. 2.1. Crude extract of T. camphoratus The ethyl acetate extract also inhibited cell viability of hepa- toma Hep 3B cells by inducing apoptotic cell death with the þ Peng et al19 shook air-dried T. camphoratus powder with phos- increased level of Ca2 in the cytoplasm and triggering the phate-buffered saline at the ratio of 1:25 (w/v) at 25C for 10 hours, subsequent activation of calpain and caspase-12. It also initiated then centrifuged the extracts, and followed by filtering through the mitochondrial apoptotic pathway through regulation of Bcl-2 a 0.2-mm pore size filter. The growth of human urinary bladder family proteins expression, release of cytochrome c, and activation cancer T24 cells was inhibited by 50 mg/mL T. camphoratus crude of caspase-9. Furthermore, the mitochondrial apoptotic pathway 2þ extract in G2/M phase by suppressing the active form of matrix amplified the calpain pathway by Bid and Bax interaction and Ca metalloproteinase 9.14 Furthermore, they also found that 100 mg/mL translocation.23 T. camphoratus crude extract displayed antiproliferation effect in transitional cell carcinomas cell lines RT4, TSGH-8301, and T24. RT4 2.4. CHCl3 extract from the fruiting bodies cells may proceed the p53-independent overexpression of p21 with simultaneous down alteration of pRb, and which was speculative of The powdered fruiting bodies were extracted with CHCl3 at proceeding through a mechanism of replicative senescence. In the room temperature. After filtration, the solvent was evaporated contrast, growth inhibitions of TSGH-8301 and T24 as affected by under reduced pressure to obtain CHCl3 extracts. It showed simultaneous downregulations of Cdc2 and cyclin B1 were attrib- cytotoxic activity against Jurkat (human lymphocytic cancer uted to the insufficient and destabilized Cdc2-cyclin B1 complex cell line), Hep G2, Colon 205 (human colon cancer cell line), formation. In another study,20 prostate cancer cell lines LNCaP and MCF-7 (human breast cancer cell line) because of the (androgen responsive) showed a G1/S phase arrest
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