2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) is a cyclohexanedione found in the roots of Averrhoa carambola L., commonly known as starfruit. Researchers have shown that DMDD has significant therapeutic potential for the treatment of diabetes; however, the effects of DMDD on human cancers have never been reported. We investigated the cytotoxic effects of DMDD against human breast, lung and bone cancer cells in vitro and further examined the molecular mechanisms of DMDD-induced apoptosis in human breast cancer cells. DMDD suppressed the growth of breast carcinoma cells, but not normal mammary epithelial cells, via induction of G1 phase cell cycle arrest, oxidative stress and apoptosis. DMDD increased the level of intracellular reactive oxygen species (ROS) and DMDD-induced ROS generation was found to be associated with the mitochondrial activity. The cytotoxicity that was induced by DMDD was attenuated by co-treatment with the antioxidant N-acetyl-L-cysteine (NAC). DMDD-induced cell apoptosis involved the activation of both the intrinsic mitochondrial pathway and the extrinsic receptor pathway. In addition, DMDD inhibited the canonical NF-κB signaling pathway at all steps, including TNF-α production, phosphorylation of NF-κB p65 and IκBα, as well as TNF-α activated NF-κB p65 nuclear translocation. Collectively, our studies indicate that DMDD has significant potential as a safe and efficient therapeutic agent for the treatment of breast cancer.

Abstract. Naturally derived stilbenes have been shown to elicit cytotoxic, anti-steroidal, anti-mutagenic, anti-oxidative, anti-inflammatory, and antitumor bioactivities. Previous phytochemical studies revealed that the seeds of Paeonia suffruticosa are rich in natural stilbenes. In this study the antitumor effects and mechanism of action of the oligostilbene isomers, cis-and trans-suffruticosol D, isolated from the seeds of P. suffruticosa were examined. cis-and transsuffruticosol D exhibited remarkable cytotoxicity against the human cancer cell lines A549 (lung), BT20 (breast), MCF-7 (breast), and U2OS (osteosarcoma), but showed significantly less toxicity to the normal human cell lines HMEC (breast) and HPL1A (lung). We also demonstrated that cis-and transsuffruticosol D exerted their antitumor effects by provoking oxidative stress, stimulating apoptosis, decreasing the mitochondrial membrane potential, inhibiting cell motility, and blocking the NF-κB pathway in human lung cancer cells. In addition, we evaluated their respective bioefficacy and found that trans-suffruticosol D is more potent than cissuffruticosol D. Collectively, our results suggest that cis-and trans-suffruticosol D could be promising chemotherapeutic agents against cancer. IntroductionCurrent cancer medications are costly and often cause serious side effects. The US National Cancer Institute began investigating antitumor plant extracts in the 1960s, and the premise that natural compounds obtained from therapeutic plants could produce anticancer medications has henceforth been of great research interest. Traditional Chinese medicines (TCMs) using dried plants or plant extracts have provided low cost diet and pharmaceutical therapies for thousands of years and experimental and clinical studies have proven that >400 plant species used in TCMs as anticancer herbal medications are significantly effective in the prevention or treatment of various cancers (1-4). However, much work remains to be done to determine the effectiveness of the individual compounds present in the TCMs.Paeonia suffruticosa, or Paeoniaceae, is a widely utilized Chinese medicinal plant within the Paeonia genus. This genus comprises ~35 species that are classified into three groups: Oneapia, Paeonia, and Moutan (5). The Cortex Moutan (root cortex) of Paeonia has been recorded by China's Pharmacopoeia as a significant source of herbal medicine (6). Extracts of Paeonia have been shown to possess cytotoxic, antitumor, anti-inflammatory and anti-oxidative activities (5). Previous photochemical research on Paeonia identified >260 bioactive compounds, including phenols, monoterpenoidglucosides, paeonols, flavonoids, tannins, steroids, triterpenoids and stilbenes (7). A more recent study showed that the seeds of Paeonia contain considerable quantities of stilbenes compared to the other compounds (7,8).Stilbenes are a class of polyphenols widely found in plants that contain a 1.2-diphenylethylene nucleus in their structure (9). Stilbenes have aroused great interest due to their antit...

Aurone derivatives devoid of the unusual oxygenation found in the coumaranone fragment are potential leads for new anti-cancer agents.

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We demonstrated that cis- and trans-gnetin H suppress cytokine response in LPS-stimulated THP-1 cells by preventing activation of key signaling molecules, IKK-β, IκB α, and p65, involved in the NF-κB pathway and suggest the use of cis- and trans-gnetin H in potential therapies for conditions and diseases associated with chronic inflammation.

Abstract.A total of five matrine derivatives were synthesized and evaluated for their anti-proliferation activity using a panel of four human cancer cell lines, including A549 lung, BT20 breast, MCF-7 breast and U2OS osteosarcoma cells. The YF3-5, YF3-7 and YF3-9, three novel compounds, demonstrated increased anti-proliferation activity compared with matrine, of which YF3-5 revealed the strongest anti-proliferation activity with a half-maximal inhibitory concentration value of 15.49-16.67 µM against the four human cancer cell lines. The anti-proliferation mechanism underlying YF3-5 was investigated in the A549 human lung cancer cell line and the results demonstrated that YF3-5 exerted its anti-proliferation activity through the induction of apoptosis and oxidative stress, in addition to arresting the cell cycle at the G 1 phase in a dose-dependent manner. IntroductionLung cancer is the primary cause of cancer-associated mortalities and is ranked the highest in males and second highest in females for mortality and morbidity rates globally (1). Non-small cell lung cancer (NSCLC), which constitutes 80-85% of lung cancer cases, remains an aggressive type of lung cancer that is associated with poor patient survival (2). Currently, chemotherapy has reached a plateau of effectiveness in improving patient survival, and it is the mainstay of treatment regimens and new drugs, including erlotinib and gefitinib, that they will eventually fail due to drug resistance (3,4); therefore, novel approaches and drugs are urgently required in order to improve the prognosis of patients with lung cancer.Natural compounds remain a predominant source for anticancer drug development. A total of 47% of the 155 anticancer drugs approved from 1950-2006 were natural products or directly derived from them (5). Matrine (C 15 H 24 N 2 O) is the major alkaloid component identified in Sophora alopecuroides roots, which are widely utilized in traditional Chinese medicine and have a wide range of pharmacological effects, including anti-cardiac, anti-arrhythmic, anti-bacterial, anti-asthma, anti-diuretic, immune suppressive and anti-inflammatory activities (6-9). It has also been reported that matrine possesses antitumor activities in vitro and in vivo (10-13). The mechanisms underlying matrine's antitumor activities include the inhibition of cell proliferation and the induction of apoptosis (14-16). However, the low water solubility, bioavailability and bioactivity of matrine, coupled with its considerable side effects, which include general toxicity to the central nervous system, have limited its utility as a therapeutic drug (17,18). Therefore, studies have been focusing on developing derivatives and analogues of matrine by total synthesis or structural modifications in order to improve its activity and bioavailability (19)(20)(21).A previous study demonstrated that the amide bond may be required for the antitumor activities of matrine as following opening of the D-ring and breaking of the amide bond, the anti-proliferative activities of matrine ...

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Background:The oligostilbenes cis-and trans-gnetin H were previously studied for their ability to inhibit cancer cell proliferation and induce apoptosis. However, an in-depth understanding of the proteins involved in this process remains poorly understood. Methods: The ability of cis-and trans-gnetin H to act as an antioxidant by scavenging one of the stable free radicals DPPH was tested. We also tested the ability of both compounds to generate oxidative stress through elevating the reactive oxygen species (ROS) resulting in apoptosis using lung cancer cell line A549. Also, immunoassay Enzyme-linked Immunosorbent Assay (ELISA) was performed to test the levels of the major apoptotic proteins using a negative estrogen receptor (ER-) breast cancer cell line MDA-MB-231.Results: Cis-and trans-gnetin H treatment showed a high percentage of the radical scavenging activity =%24 at the lowest concentration 12.5μM (p≤0.0001) and elevated the levels of ROS in A549 to 50%, 45%, respectively (p≤0.001). In addition, cis-and trans-gnetin H induced early apoptosis in A549 cell line to 59% and 38.9%, respectively, at the highest concentration of 25μM compared to the untreated control (p≤0.0001). Results from apoptosis protein array showed certain up-regulated proteins such as Bid, Bad, cytochrome c, FasL, TRAIL1-4 and down regulated proteins such as XIAP, surviving, Hsp60, suggesting inducing apoptosis was facilitated by cross talk between intrinsic and extrinsic pathway through TRAIL pathway. Conclusion:These observations suggested that cis-and trans-gnetin H induces apoptosis in human lung and breast cancer cells in vitro through elevating the levels of oxidative stress and directly affecting the primary regulator of apoptosis proteins.