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  • br were lower than IC of normal fibroblast


    were lower than IC50 of normal fibroblast cells (L929). Etoposide was used as a positive control since this
    chemotherapeutic drug is in the lignan group same as ( ± )-kusunokinin. Surprisingly, etoposide showed less
    ( ± )-bursehernin induced G-418 Sulfate arrest at G2/M phase, meanwhile ( ± )-kusunokinin tended to increased cell
    population at G2/M phase but did not show the significant difference compared with non-treated cells.
    Interestingly, protein levels related to cell proliferation pathway (topoisomerase II, STAT3, cyclin D1, and p21)
    were significantly decreased at 72 h. Both compounds induced apoptotic cell in time-dependent manner as
    confirmed by MultiCaspase assay. In conclusion, synthetic compound, ( ± )-kusunokinin and ( ± )-bursehernin,
    showed anticancer effects via the reduction of cell proliferation proteins and induction of apoptosis.
    1. Introduction
    Cancer is the second leading cause of death in the world. In 2018, there were approximately 18.1 million new cancer cases and 9.6 million cancer deaths. According to estimates from the World Health Organization (WHO), lung, prostate, colorectal, stomach and liver cancer are the most common types of cancer in men, while breast, colorectal, lung, cervix and thyroid cancer are the most common in women [1]. In Thailand, breast, cervix, colorectal, liver and lung cancer are the most five commonly found [2]. However, cholangiocarcinoma, a bile duct cancer, shows the highest world incidence, especially in Northeastern part of Thailand [3].
    Chemotherapy is the general choice G-418 Sulfate for cancer treatment, however chemotherapeutic drugs have many adverse effects such as
    immunosuppression, myelosuppression, gastrointestinal toxicity, and cancer drug resistance [4]. Therefore, searching for new effective cancer therapeutic agent which extracted from natural source is on-going. Three major groups of natural compound for cancer treatment include alkaloids, flavonoids, and lignans. The anticancer alkaloid compounds from plant are paclitaxel®, camptothecin, rohitukine, and harringtonine [5]. The flavonoid compounds are flavopiridol, genistein, quercetin, and myricetin [6]. The potent anticancer compounds in lignan group are, masoprocol [7] and daurinol [8]. In addition, eto-poside and teniposide are chemotherapeutic drug in lignan group [7].
    Corresponding author at: Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Songkhla, 90110, Thailand. E-mail address: [email protected] (P. Graidist).
    T. Rattanaburee, et al.
    Wikstroemia sikokiana [13], and Piper nigrum [14]. Kusunokinin from A. cymbifera show antitrypanosomal and anti-human leukemic monocyte (THP-1 cells) [15]. Moreover, (-)-kusunokinin from roots and leaves of A. malmeana show biological activity against Anticarsia gemmatalis with LD10 of 9.30 μg/ml (35.60 μM) and LD50 of 230.1 μg/ml (880.82 μM) [10]. Our previous study found that (-)- kusunokinin from P. nigrum had an effect on breast cancer cell lines by cell growth inhibition, induction of cell cycle arrest at G2/M phase and induction of apoptosis [14].
    Bursehernin, (3R,4R)-4-(1,3-benzodioxol-5-ylmethyl)-3-[(3,4-di-methoxyphenyl)methyl] oxolan-2-one or 5´-desmethoxyyatein, is a lignan compound extracted from many plants such as Bursera fagaroides [16], Macrococculus pomiferus [17], Bursera simaruba Sarg. [18], Linum meletonis [19], and Geranium thunbergii [20]. This compound has a
    Table 1
    The half maximal inhibitory concentration (IC50) values of ( ± )-kusunokinin and ( ± )-bursehernin for inhibition of viability of cancer and normal cell lines.
    Cell lines Compounds IC50(μM)
    ( ± )-kusunokinin ( ± )-bursehernin etoposide
    Data are presented mean ± SD form at least three independent experiments. a p < 0.05 significantly different compared with etoposide.