br Bursehernin vestigated for their
Bursehernin vestigated for their anticancer activities on cell viability, U-0126 arrest and apoptosis in cancer cell lines
Anticancer including breast cancer (MCF-7, MDA-MB-468 and MDA-MB-231), colon cancer (HT-29) and cholangiocarci-
sehernin represented the strongest growth inhibition against breast cancer (MCF-7) and cholangiocarcinoma
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 cell cycle 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.
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 . In Thailand, breast, cervix, colorectal, liver and lung cancer are the most five commonly found . However, cholangiocarcinoma, a bile duct cancer, shows the highest world incidence, especially in Northeastern part of Thailand .
Chemotherapy is the general choice for cancer treatment, however chemotherapeutic drugs have many adverse eﬀects such as
immunosuppression, myelosuppression, gastrointestinal toxicity, and cancer drug resistance . 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 . The flavonoid compounds are flavopiridol, genistein, quercetin, and myricetin . The potent anticancer compounds in lignan group are, masoprocol  and daurinol . In addition, eto-poside and teniposide are chemotherapeutic drug in lignan group .
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 , and Piper nigrum . Kusunokinin from A. cymbifera show antitrypanosomal and anti-human leukemic monocyte (THP-1 cells) . 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) . 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 .
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 , Macrococculus pomiferus , Bursera simaruba Sarg. , Linum meletonis , and Geranium thunbergii . This compound has a
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.
c p < 0.05 significantly diﬀerent compared with MMNK-1 cells.
Fig. 3. Cell cycle analysis of ( ± )-kusunokinin and ( ± )-bursehernin treated cancer cells.
(A, C) MCF-7 and (B, D) KKU-M213 cells were treated with IC50 concentration of 4.30 μM ( ± )-kusunokinin or 3.70 μM ( ± )-bursehernin for 24, 48 and 72 h. To determine the cell distributions in each phase of the cell cycle, treated cell were stained with PI and measured DNA content using MUSE® Cell Analyzer. Data represent the mean ± SD of two independent experiments. Statistical significantly was determined with Student t-test. p value less than 0.05 was considered to indicate a statistically significant diﬀerences compared to control group at 0 h.