br activity CK exerts anti cancer effects

40 activity, CK exerts anti-cancer effects by inducing apoptosis.
41 Conclusion: Our results suggest that CK could be used as a therapeutic compound for breast
43 44 Keywords: Compound K; Panax ginseng; AKT1; cancer; apoptosis
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47 Breast cancer is the most common type of cancer in women. Every year, approximately
48 500,000 deaths occur in women worldwide due to breast cancer, which is the second leading
49 cause of global death in women [1,2]. Although many methods of diagnosis and treatment of
50 breast cancer have developed, and patients are offered various treatment options such as
51 chemotherapy, radiotherapy, and endocrine therapy, the incidence of breast cancer is still
52 increasing rapidly [3]. Breast cancer is a heterogeneous disease represented by conditions
53 with unique histopathological and molecular characteristics. Tumors are characterized based
54 on the responsiveness of ER (estrogen receptor), PR (progesterone receptor), and HER2
55 (human epithelial growth factor receptor-2). Approximately 15-20% of breast cancer patients
56 overexpress HER2, leading to a high risk of relapse and a short survival period [4]. Although
57 many drugs targeting HER2-positive breast cancer have been developed, conventional 58 treatments are not very successful. Therefore, it is very important to study other
59 chemotherapeutic drugs that can effectively treat breast cancer, especially HER2-positive
60 breast cancer.
61 62 Tumors are caused by imbalance of cell proliferation and apoptosis. Since the apoptosis
63 mechanism induces programmed cell death, approaches to suppress the growth of cancer
64 CY7-SE and induce cell death by up-regulating the apoptosis pathway have been widely studied
65 for cancer treatment. Numerous studies have reported a variety of cancer treatments
66 involving activation of the apoptosis mechanism [5]. Among them are numerous natural,
67 plant-derived compounds that have excellent cancer-suppressing activity via the apoptosis
69 apoptosis can be an effective strategy for development of anticancer drugs.
70 71 The roots of Korean ginseng (Panax ginseng Meyer) have been widely used as herbal 72 medicines in East Asia. In particular, the biological and pharmacological effects of
73 ginsenoside, a major bioactive component of ginseng, have been actively investigated [7].
74 Various pharmacological activities of ginsenosides, including neuroprotective, anti-cancer,
75 and anti-inflammatory activities, have been reported [8,9]. Compound K (CK), an active
76 ingredient of ginsenoside and a novel ginseng saponin metabolite, has recently been found.
77 This compound is formed through deglycosylation of ginsenosides Rb1, Rb2, and Rc by
78 human intestinal bacteria. CK has cardioprotective, anti-inflammatory, and liver-protection
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80 anticancer activity in triple-negative breast cancer [16]. However, the activity and biological
81 mechanism of CK in breast cancer are not fully understood. The aims of this study were to
82 investigate the ability of Compound K to regulate cell proliferation and apoptosis in SKBR3
83 human breast cancer cells and to elucidate the molecular mechanism of its activity.
90 (RPMI1640) medium, fetal bovine serum (FBS), and phosphate-buffered saline (PBS) were
92 dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide (MTT), hematoxylin, eosin, and
93 sodium dodecyl sulfate (SDS) were purchased from Sigma Chemical Co. (St. Louis, MO,
94 USA). PI and annexin V staining kits were purchased from BD Biosciences (Franklin Lakes, 95 NJ, USA). Total or phospho-specific antibodies were obtained from Cell Signaling
100 negative breast cancer cell line) were cultured in RPMI 1640 (HyClone, USA) medium with
101 10% heat-inactivated FBS and 1% penicillin and streptomycin at 37°C and 5% CO2. For each 102 experiment, trypsin was used to detach the SKBR3 cells, and the stock solution of CK was
106 SKBR3 cells (5x105 cells/ml) were seeded in 96-well plates for 18 h and then incubated 107 with varying concentrations of CK. After the indicated times, cell viability was measured
108 using a conventional MTT assay as described previously [17] .
111 SKBR3 cells were plated and incubated overnight. The cells were treated with CK for 6 h,
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112 collected, and washed with PBS. The cells were then stained with two apoptotic markers
113 following the manufacturer’s instructions.