Anti-proliferative and pro-apoptotic effect of Smilax glabra Roxb. extract on hepatoma cell lines

Institute of Chinese Medical Sciences, University of Macau, Av. Padre Tomás Pereira S.J., Taipa, Macao, China.
Chemico-Biological Interactions (Impact Factor: 2.58). 02/2008; 171(1):1-14. DOI: 10.1016/j.cbi.2007.08.012
Source: PubMed


Smilax glabra Roxb. (SGR) is the root of a traditional Chinese herb, referred to as tu fu ling in Chinese medicine. It is an inexpensive traditional Chinese medicine commonly used for the treatment of liver diseases, and a few studies have indicated that SGR has anti-hepatocarcinogenic and anti-cancer growth activities. In the current study, raw SGR plant was extracted with Accelerate Solvent Extractor, and the molecular mechanism by which S. glabra Roxb. extract (SGRE) has an anti-proliferative effect on the human hepatoma cell lines, HepG2 and Hep3B, was determined. We showed that SGRE inhibited HepG2 and Hep3B cell growth by causing cell-cycle arrest at either S phase or S/G2 transition and induced apoptosis, as evidenced by a DNA fragmentation assay. SGRE-induced apoptosis by alternation of mitochondrial transmembrane depolarization, release of mitochondrial cytochrome c, activation of caspase-3, and cleavage of poly(ADP-ribose) polymerase. The SGRE-mediated mitochondria-caspase dependent apoptotic pathway also involved activation of p38, JNK, and ERK mitogen-activated protein kinase signaling. Isometric compounds of astilbin (flavonoids) and smilagenin (saponin) have been identified as the main chemical constituents in SGRE by HPLC-MS/MS. These results have identified, for the first time, the biological activity of SGRE in HepG2 and Hep3B cells and should lead to further development of SGR for liver disease therapy.

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Available from: Ying Zheng, Dec 03, 2014
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    • "Smilax china (family Liliaceae) is a native plant grown in China, Japan, and Korea, and its root has been used as emergency foods in the past (Huang and others 2008, 2009; Kang and others 2011). It has also been used as a folk medicine for leptospirosis, syphilis, brucellosis , rheumatoid arthritis, nephritis, detoxification, and heavy metal poisoning (Chen and others 2000; Chu and Ng 2006; Sa and others 2008; Xia and others 2010; Shim 2012b). Although the Smilax china root contains important bioactive components including resveratrol and oxyresveratrol, nowadays most of them are thrown out because it refrains other trees from photosynthesis through spiraling. "
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    ABSTRACT: Unlabelled: Resveratrol has a beneficial effect of lowering reactive oxygen species (ROS) and reduces cellular oxidative stress. We hypothesized that ethanol extract of Smilax china root (EESC) rich in resveratrol (RES) and oxyresveratrol (OXY) could reduce ROS caused by nicotine and promoting nicotine turnover by induction of CYP2A6. The amount of cotinine converted from nicotine was quantified by the direct barbiturate assay method. Expression of CYP2A6 was unregulated by RES, OXY, or EESC, respectively. Pretreatment of RES (50, 100, and 250 μM), OXY (50, 100, and 250 μM), and RES+OXY (50 and 100 μM) inhibited cytotoxicity and ROS production caused by nicotine in a dose-dependent manner. EESC pretreatment (1.8 mg/mL) increased cell viability by 1.5-fold higher than the control (nicotine only), and lowered cellular ROS levels. A significant amount of the conversion of nicotine to cotinine was observed in EESC pretreatment by CYP2A6 induction in HepG2 cells. These results suggested that hepatic induction of CYP2A6 and ROS reduction by EESC activate nicotine metabolism and reduce cellular oxidative stress. Practical application: Nicotine exposure due to smoking is very concerning because it is the major factor for lung diseases and cardiovascular disorders. It is necessary to examine natural ingredients that can detoxify from nicotine to cotinine as well as neutralize free radicals induced from nicotine. Results from the current study suggest potential applications of Smilax china root for detoxification of nicotine in the food industry.
    Journal of Food Science 10/2014; DOI:10.1111/1750-3841.12595 · 1.70 Impact Factor
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    • "Smilax glabra Roxb. extractmediated mitochondria-caspase-dependent apoptotic pathway , however, involves p38, JNK, and ERK signalling activation (Sa et al., 2008). Our previous studies have demonstrated that p-PD induced apoptosis through p53, as well as intrinsic and extrinsic pathways in Mardin-Darby canine kidney (MDCK) cells (Chen et al., 2006; 2010). "
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    ABSTRACT: para-phenylenediamine (p-PD) is a suspected carcinogen, but it has been widely used as a component in permanent hair dyes. In this study, the mechanism of p-PD-induced cell death in normal Chang liver cells was investigated. The results demonstrated that p-PD decreased cell viability in a dose-dependent manner. Cell death via apoptosis was confirmed by enhanced DNA damage and increased cell number in the sub-G1 phase of the cell cycle, using Hoechst 33258 dye staining and flow cytometry analysis. Apoptosis via reactive oxygen species generation was detected by the dichlorofluorescin diacetate staining method. Mitogen-activated protein kinase (MAPK) activation was assessed by western blot analysis and revealed that p-PD activated not only stress-activated protein kinase (SAPK)/c-Jun N-terminal kinases (JNK) and p38 MAPK but also extracellular signal-regulated kinase (ERK). Cytotoxicity and apoptosis induced by p-PD were markedly enhanced by ERK activation and selectively inhibited by ERK inhibitor PD98059, thus indicating a negative role of ERK. In contrast, inhibition of p38 MAPK activity with the p38-specific inhibitor SB203580 moderately inhibited cytotoxicity and apoptosis induction by p-PD. Similarly, SP600125, an inhibitor of SAPK/JNK, moderately inhibited cytotoxicity and apoptosis induced by p-PD, thus implying that p38 MAPK and SAPK/JNK had a partial role in p-PD-induced apoptosis. Western blot analysis revealed that p-PD significantly increased phosphorylation of p38 and SAPK/JNK and decreased phosphorylation of ERK. In conclusion, the results demonstrated that SAPK/JNK and p38 cooperatively participate in apoptosis induced by p-PD and that a decreased ERK signal contributes to growth inhibition or apoptosis. © 2012 Wiley Periodicals, Inc. Environ Toxicol, 2012.
    Environmental Toxicology 09/2014; 29(9). DOI:10.1002/tox.21828 · 3.20 Impact Factor
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    • "For example, it was shown that the Smilax glabra Roxb. extract (SGRE)-mediated mitochondria-caspase dependent apoptotic pathway involves activation of p38, JNK, and ERK signaling [22], while Sulforaphane induced apoptosis via JNK-caspase-2 in advanced colon carcinoma [23]. Furthermore, cytotoxic lipid peroxides 4-hydroxy-2-nonenal (HNE) induces apoptosis of PC12 cells also through the activation of the JNK pathway without activation of ERK or p38 MAPK [24]. "
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    ABSTRACT: Butyrate has been shown to display anti-cancer activity through the induction of apoptosis in various cancer cells. However, the underlying mechanism involved in butyrate-induced apoptosis is still not fully understood. Here, we investigated the cytotoxicity mechanism of butyrate in human colon cancer RKO cells. The results showed that butyrate induced a strong growth inhibitory effect against RKO cells. Butyrate also effectively induced apoptosis in RKO cells, which was characterized by DNA fragmentation, nuclear staining of DAPI, and the activation of caspase-9 and caspase-3. The expression of anti-apoptotic protein Bcl-2 decreased, whereas the apoptotic protein Bax increased in a dose-dependent manner during butyrate-induced apoptosis. Moreover, treatment of RKO cells with butyrate induced a sustained activation of the phosphorylation of c-jun N-terminal kinase (JNK) in a dose- and time-dependent manner, and the pharmacological inhibition of JNK MAPK by SP600125 significantly abolished the butyrate-induced apoptosis in RKO cells. These results suggest that butyrate acts on RKO cells via the JNK but not the p38 pathway. Butyrate triggered the caspase apoptotic pathway, indicated by an enhanced Bax-to-Bcl-2 expression ratio and caspase cascade reaction, which was blocked by SP600125. Taken together, our data indicate that butyrate induces apoptosis through JNK MAPK activation in colon cancer RKO cells.
    Chemico-biological interactions 03/2010; 185(3):174-81. DOI:10.1016/j.cbi.2010.03.035 · 2.58 Impact Factor
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