Induction of caspase cascade pathway by kaempferol-3-O-rhamnoside in LNCaP prostate cancer cell lines

Abstract

Abstract.Prostate cancer has become a leading cause of mortality in humans. Previous studies have shown the potential anticancer properties of kaempferol-3-O-rhamnoside in breast cancer cell lines. In the present study, the anticancer potential of kaempferol-3-O-rhamnoside was investigated in LNCaP human prostate cancer cell lines. The inhibition of cell proliferation was investigated using MTT assays, whereas its ability to induce the caspase-cascade pathway was investigated by western blotting. The results showed that kaempferol-3-O-rhamnoside inhibits the proliferation of LNCaP cells in a dose-dependent manner by upregulating the expression of caspase-8, caspase-9, caspase-3 and poly (ADP-ribose) polymerase proteins. Although further studies are required, the results of the present study indicate the potential application of kaempferol-3-O-rhamnoside in cancer treatment. IntroductionCancer has become a significant disease for humans. In the USA alone, there were ~1.6 million new cases and 577,190 predicted mortalities in 2012. Among all types of cancer, prostate cancer is one of the top causes of male cancer fatalities worldwide (1). It is predicted that 233,000 new cases of prostate cancer will occur in America during 2014 (2).Several treatments are available for treatment of prostate cancer, by overcoming the aggressive tumor. These include surgery, radiation, radioactive implants and hormonal therapy. However, the treatment often impacts the quality of life due to side-effects or complications (3). Thus, numerous investigators have focused on discovering novel drugs or treatments. Among all the agents tested, natural products derived from medicinal plants are among the most favorable.In our previous study, kaempferol-3-O-rhamnoside, the major compound found in the ethyl acetate fractions of the Schima wallichii (S. wallichii) Korth. leaves, was isolated and its properties were investigated against breast cancer cell lines. The results indicated that kaempferol-3-O-rhamnoside was favorable for further exploration of its anticancer therapeutic potential (4). Therefore, in the present study the anticancer properties and mechanism of kaempferol-3-O-rhamnoside were investigated in prostate cancer cell lines. Materials and methodsPlant materials. S. wallichii Korth. leaves were collected from Lembang, West Java, Indonesia. The plant species was identified at the Department of Biology, Faculty of Mathematics and Natural Sciences, University of Padjadjaran (West Java, Indonesia).Extraction and isolation. The S. wallichii leaves were dried and extracted with 70% ethanol at room temperature three times for 24 h each. A concentrated extract was obtained in vacuo at 50˚C. The ethanol extract was partitioned into n-hexane, ethyl acetate and aqueous phases. Column chromatography on a Wakogel C 200 (Wako Pure Chemical Industries, Ltd., Osaka, Japan) column was performed to the ethyl acetate fraction, as it was previously reported as the most active fraction against cancer cell lines, using a mixture of n-hexane, ethyl ac...

Cytotoxic activity and apoptotic induction of some edible Thai local plant extracts against colon and liver cancer cell lines

“…The results using S. wallichii extract were similar to those of Halimah et al [24] who showed that the major compound (kaempferol-3-Orhamnoside) in the ethylacetate fraction of. S. wallichii inhibited MCF-7 cell growth via activation of caspase-9 and caspase-3, inducing apoptosis.…”

Chemo‐preventive and therapeutic effect of the dietary flavonoid kaempferol: A comprehensive review

“…In a similar fashion, treatment with kaempferol inhibited proliferation of gastric cancer cell lines MKN28 and SGC7901 through multiple mechanisms; it (a) induced apoptotic cell death, (b) exhibited cell cycle arrest, (c) suppressed tumor growth, (d) decreased cyclin B1, Cdk1, and Cdc25C expressions, (e) lowered Bcl‐2 and enhanced Bax expressions, (f) upregulated cleaved caspase‐3 and ‐9, (g) promoted Poly (ADP‐ribose) polymerase (PARP) cleavage, and (h) decreased p‐Akt, p‐ERK and cyclooxygenase‐2 (COX‐2) expression levels (Song et al, ). Furthermore, kaempferol‐3‐ O ‐rhamnosidedose, a derivative of kaempferol, suppressed cell proliferation rate, induced caspase‐cascade pathway, upregulated the expression of caspase‐3, caspase‐8, caspase‐9, and PARP proteins in LNCaP human prostate cancer cell lines in a concentration‐dependent manner (Halimah et al, ).…”

Kaempferol – A dietary anticancer molecule with multiple mechanisms of action: Recent trends and advancements

“…Recent in vitro and in vivo studies have shown the antiproliferative and proapoptotic activities of KMF against various types of cancers including breast (Azevedo et al, 2015;Kim, Hwang, & Choi, 2016;Liao et al, 2016), ovarian (Luo, Rankin, Li, Depriest, & Chen, 2011), lung (Kuo et al, 2015), pancreas (Zhang, Chen, Li, Chen, & Yao, 2008), esophagus (Yao et al, 2016), stomach , colon , prostate (Halimah et al, 2015), bladder (Dang et al, 2015), kidney (Song et al, 2014) and others. Most of these studies demonstrate that the mechanism of KMF is dependent on the inhibition of proliferation of various cancer cells either via cell cycle arrest or induction of apoptosis (Kuo et al, 2015;Liao et al, 2016).…”