In Vitro Anti‐Tumour Activities of Quinolizidine Alkaloids Derived from Sophora Flavescens Ait

Abstract

Abstract:The dry root of Sophora flavescens Ait. (SF) has long been used in a variety of Chinese herbal formulations to treat patients with cancer. Alkaloids are commonly known to present in SF as main active constituents. Here, we report that among the six characterized SF-derived quinolizidine alkaloids including sophoridine, aloperine, sophocarpine, matrine, oxymatrine and cytisine, aloperine exerted the most potent in vitro cytotoxic activity against the human cancer cell lines and oxymatrine exhibited selective anti-cancer activity against hepatocellular carcinoma HepG2 cells. Analysis of DNA fragmentation and PARP cleavage revealed that aloperine treatment for 48 hr induced apoptosis in HL-60 cells. In addition, autophagic formation of acidic vacuole was also observed in HL-60 cells exposed to aloperine. These results suggest that aloperine may be a novel contributor to the anti-cancer properties of SF.The dry root of Sophora flavescens Ait. (SF) (Leguminosae), also referred to as Kushen, has a long history of use in a variety of traditional Chinese medicine herbal formulations to treat a range of diseases, including cancer, viral hepatitis, cardiac arrhythmia and skin diseases [1-4]. As higher percentage of alkaloids is found in SF (3.3%), SF alkaloids have received much attention in the past decades in China as the bioactive substances [5,6]. For example, SF alkaloids are demonstrated to be the potential chemopreventive and chemotherapeutic agents, and they contribute to the therapeutic anti-cancer activity of SF. Alkaloids injection prepared from SF has been approved to treat patients with cancer by the Chinese State Food and Drug Administration (SFDA) in 1992. Clinical studies have demonstrated that the injection is a safe and effective remedy for the treatment of various types of cancer [7,8].Quinolizidine alkaloids have been identified to be the major components of SF alkaloids [9]. Quinolizidine alkaloids represent about 2% of the known alkaloids from plants [10], and most of them were initially noticed as constituents of plants poisonous to humans and livestock. However, accumulated evidence indicates that some of them exhibit potentially useful pharmacological properties like anti-cancer, anti-bacterium, anti-virus, anti-inflammation and pain relief [11]. Quinolizidine alkaloids can be divided into more than six structural groups such as matrine-type, aloperinetype and cytisine-type. Matrine-type alkaloids such as matrine, oxymatrine, sophocarpine and sophoridine are commonly purified from SF [9]. Although previous studies demonstrate that matrine-type alkaloids mediate growth inhibition in different types of cancer cells, the reported IC 50 values are generally not lower than 0.5 mM [12][13][14][15][16]. It seems that the alkaloids other than matrine-type may contribute to the anti-neoplastic activities of SF alkaloids. Previous reports indicate that both aloperine and cytisine are also the characterized components in SF [9,17,18], but inspection of the literature data reveals that the potential ...

Fufang Kushen injection inhibits sarcoma growth and tumor-induced hyperalgesia via TRPV1 signaling pathways

“…Quinolizidine alkaloids, like matrine, appear to inhibit tumor cell growth by driving apoptosis through mitochondrial dependent signal cascades [45]. However, in our studies matrine at equal dosing was not as effective as FKI at inhibiting S-180 growth or signal cascades including pBAD, suggesting that the formulation of FKI results in an enhanced response over the effect of individual chemicals.…”

Aloperine Protects Mice against Ischemia-Reperfusion (IR)-Induced Renal Injury by Regulating PI3K/AKT/mTOR Signaling and AP-1 Activity

“…However, pretreatment of mice with aloperine prevented tubular cells from IRinduced apoptosis as evidenced by the significant reduction of TUNELpositive tubular cells and decreased protein levels for caspase3. This finding somehow is in conflict with studies in tumor cells in which aloperine was noted to promote cancer or tumor cell apoptosis (26,66). To confirm this observation, we cultured HK2 cells under hypoxic conditions in the presence of aloperine and similar results were obtained (data not shown).…”

“…Previous studies have consistently demonstrated that aloperine, an alkaloid extracted from sophora alopecuroides, possesses beneficial properties against inflammation, tumor growth and infec tion (24)(25)(26)(27)(28). As a result, it has been used widely in clinical settings for the treat ment of inflammatory diseases including allergic dermatitis (29).…”

Participatory Ethnomedicinal Cancer Research with Fante-Akan Herbalists in Rural Ghana

“…These two plant families are distinguished by the bioactive secondary metabolites typically produced by representative species, namely alkaloids (Lin et al 2011;Michael 2005;Wink 2003).…”