• Journal of the Korean Society of Food Science and Nutrition
• /
• v.39 no.8
• /
• pp.1119-1125
• /
• 2010

To evaluate resveratrol as a prostate cancer preventive material, we investigated its anti-proliferative and apoptotic effects in RC-58T/h/SA#4 primary human prostate cancer cells. Resveratrol significantly decreased the number of viable RC-58T/h/SA#4 cells in a dose- and time-dependent manner. Resveratrol showed cytotoxicity against RC-58T/h/SA#4, LNCaP, PC-3 human prostate cancer cells with $IC_{50}$ values of 245, 320 and $340\;{\mu}M$, respectively. However the cytotoxic potential of resveratrol against normal RWPE-1 cells was lower ($IC_{50}=982\;{\mu}M$). Resveratrol induced cell death as evidenced by the increased formation of apoptotic bodies, nuclear condensation, sub-G1 phase, and DNA fragmentation. Resveratrol activated initiator caspases 8, and 9 as well as effector caspase 3 in a dose-dependent manner. Furthermore, the general caspase inhibitor z-VAD-fmk significantly inhibited resveratrol-induced apoptosis compared to cells without treatment. These results clearly indicate that resveratrol-induced apoptosis was dependent on caspase activation. Further, resveratrol modulated the down regulation of Bcl-2 (anti-apoptotic), and Bid. However, the level of Bax (pro-apoptotic) remained unchanged. These results suggest that resveratrol induced apoptosis in RC-58T/h/SA#4 cells via a mitochondrial-mediated caspase-dependent pathway, suggesting therapeutic potential against prostate cancer.

• Journal of Ginseng Research
• /
• v.36 no.1
• /
• pp.68-77
• /
• 2012

In this study, we investigated the protective effects of processed Panax ginseng, sun ginseng (SG) against the UVB-irradiation on epidermal keratinocytes and dermal fibroblasts. Pretreatment of SG in HaCaT keratinocytes and human dermal fibroblasts reduced UVB-induced cell damage as seen by reduced lactate dehydrogenase release. We also found that SG restored the UVB-induced decrease in anti-apoptotic gene expression (bcl-2 and bcl-xL) in these cells, indicating that SG has an anti-apoptotic effect and thus can protect cells from cell death caused by strong UVB radiation. In addition, SG inhibited the excessive expression of c-jun and c-fos gene by the UVB in HeCaT cells and human dermal fibroblasts. We also demonstrated that SG may exert an anti-inflammatory activity by reducing the nitric oxide production and inducible nitric oxide synthase mRNA synthesis in HaCaT keratinocytes and human dermal fibroblasts. This was further supported by its inhibitory effects on the elevated cyclooxygenase-2 and tumor necrosis factor-${\alpha}$ transcription which was induced by UVB-irradiation in HaCaT cells. In addition, SG may have anti-aging property in terms of induction of procollagen gene expression and inhibition of the matrix metalloprotease-1 gene expression caused by UVB-exposure. These findings suggest that SG can be a potential agent that may protect against the dermal cell damage caused by UVB.

• Toxicological Research
• /
• v.26 no.2
• /
• pp.109-115
• /
• 2010

The purpose of this study was to elucidate the mechanism underlying enhanced radiosensitivity to $^{60}Co\;{\gamma}$-irradiation in human prostate PC-3 cells pretreated with berberine. The cytotoxic effect of the combination of berberine and irradiation was superior to that of berberine or irradiation alone. Cell death and Apoptosis increased significantly with the combination of berberine and irradiation. Additionally, ROS generation was elevated by berberine with or without irradiation. The antioxidant NAC inhibited berberine and radiation-induced cell death. Bax, caspase-3, p53, p38, and JNK activation increased, but activation of Bcl-2, ERK, and HO-1 decreased with berberine treatment with or without irradiation. Berberine inhibited the anti-apoptotic signal pathway involving the activation of the HO-1/NF-${\kappa}B$-mediated survival pathway, which prevents radiation-induced cell death. Our data demonstrate that berberine inhibited the radioresistant effects and enhanced the radiosensitivity effects in human prostate cancer cells via the MAPK/caspase-3 and ROS pathways.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.16 no.6
• /
• pp.1190-1196
• /
• 2002

Selaginella Tamariscina is widely used in the traditional oriental herbal medicine for its anti-inflammatory, anti-cancer effects. The effects of aqueous extracts of Selaginella Tamariscina (ST) on the cell viability and induction of apoptotic cell death were investigated in A549, Raw 264.7, C6-glioma. Jurkat and HL-60 cells. The cell viability after treating with extract of Selaginella Tamariscina was quantified by MTT assay method. The results showed that ST decreased the cell viability in HL-60 and Jurkat cells not in A549, Raw 264.7 and C6-glioma cells. And we also observed the chromatin condensation and DNA fragmentation in HL-60 and Jurkat cells. The enzyme activity of caspase-3, tightly regulated by an apoptosis activating complex, were markedly increased in HL-60 cells treated with the ST by dose-dependent manner. In conclusion, our results suggest that the extract of Selaginella Tamariscina may induce the selective apoptotic cell death in HL-60 and Jurkat cells via activation of caspase-3.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.19 no.2
• /
• pp.452-458
• /
• 2005

Cordyceps militaris is a medicinal fungus, which has been used for patient suffering from cancer in Oriental medicine. It was reported previously that C. militaris extracts are capable of inhibiting tumor growth, however, the anti-poliferative effects of human cancer cells have not been poorly understood. In this study, to elucidate the growth inhibitory mechanisms of human cancer cells by treatment of aqueous extract of C. militaris (AECM) we investigated the anti-proliferative effects of AECM in human leukemia U937 cell line. AECM treatment inhibited the growth of U937 cells and induced the apoptotic cell death in a concentration-dependent manner, which was associated with morphological changes. We observed the up-regulation of cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1) by p53-independent manner and activation of caspase-3 in AECM-treated U937 cells, however, the activity of caspase-9 was remained unchanged. Additionally, AECM treatment caused a dose-dependent inhibition of the expression of telomere regulatory gene products such as human telomere reverse transcriptase (hTERT) and telomerase-associated protein-1 (TEP-1). Taken together, these findings suggest that AECM-induced inhibition of human leukemic cell proliferation is associated with the induction of apoptotic cell death via modulation of several major growth regulatory gene products, and C. militaris may have therapeutic potential in human lung cancer.

• Journal of Microbiology and Biotechnology
• /
• v.32 no.5
• /
• pp.645-656
• /
• 2022

Gossypol, a natural phenolic aldehyde present in cotton plants, was originally used as a means of contraception, but is currently being studied for its anti-proliferative and anti-metastatic effects on various cancers. However, the intracellular mechanism of action regarding the effects of gossypol on pancreatic cancer cells remains unclear. Here, we investigated the anti-cancer effects of gossypol on human pancreatic cancer cells (BxPC-3 and MIA PaCa-2). Cell counting kit-8 assays, annexin V/propidium iodide staining assays, and transmission electron microscopy showed that gossypol induced apoptotic cell death and apoptotic body formation in both cell lines. RNA sequencing analysis also showed that gossypol increased the mRNA levels of CCAAT/enhancer-binding protein homologous protein (CHOP) and activating transcription factor 3 (ATF3) in pancreatic cancer cell lines. In addition, gossypol facilitated the cleavage of caspase-3 via protein kinase RNA-like ER kinase (PERK), CHOP, and Bax/Bcl-2 upregulation in both cells, whereas the upregulation of ATF was limited to BxPC-3 cells. Finally, a three-dimensional culture experiment confirmed the successful suppression of cancer cell spheroids via gossypol treatment. Taken together, our data suggest that gossypol may trigger apoptosis in pancreatic cancer cells via the PERK-CHOP signaling pathway. These findings propose a promising therapeutic approach to pancreatic cancer treatment using gossypol.

• Journal of the Society of Cosmetic Scientists of Korea
• /
• v.31 no.3 s.52
• /
• pp.219-236
• /
• 2005

Glycolic acid, an alpha-hydroxy acid derived from fruit and milk sugars, has been commonly used as a cosmetic ingredient since it was known to have photo-protective, anti-inflammatory effects, and anti-oxidant effect in UV-irradiated skin. However, little has been know about the functional role of glycolic acid on UV-induced skin cell proliferation. It was previously found that glycolic acid inhibited UV-induced skin tumor development in hairless mouse. As a possible mechanism of glycolic acid on the UV-induced skin tumor development, the ability of glycolic acid to inhibit the UVB-induced cell growth and possible mechanisms were investigated. Glycolic acid treatment attenuated the UV-induced cell proliferation and apoptotic cell death in the skin. In vitro study, glycolic acid inhibited the UVB-induced cell growth and apoptotic death through inhibiting caspase-3 activity. These results suggest that glycolic acid may exert the Inhibitory effect on the UVB-induced skin tumor development by regulating cell growth and apoptotic cell death.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.2
• /
• pp.703-712
• /
• 2016

Monoclonal antibodies with specific antigens have been widely used as targeted therapy for cancer. Hep88 mAb is a monoclonal antibody which shows specific binding with anti-cancer effects against the HepG2 cell line. However, its mechanisms of action are still not completely understood. We examined cell cycling and apoptosis by flow cytometry and mRNA expression of factors involved in apoptosis and paraptosis in Hep88 mAb-treated HepG2 cells by real-time PCR. The cell-cycle analysis demonstrated that growth-inhibitory activity was associated with G2/M cell cycle arrest. Hep88 mAb induced a significant increase in apoptotic cell populations in a dose- and time-dependent manner. The mRNA expression results also suggested that the process triggered by Hep88 mAb involved up-regulation of tumor suppressor p53, pro-apoptotic Bax, Cathepsin B, Caspase-3 and Caspase-9, with a decrease of anti-apoptotic Bcl-2 - thus confirming paraptosis and apoptosis programmed cell death. These findings represent new insights into the molecular mechanisms underlying the anti-cancer properties of Hep88 mAb in liver cancer cells.

• International Journal of Oral Biology
• /
• v.41 no.4
• /
• pp.183-190
• /
• 2016

Anthricin (Deoxypodophyllotoxin), a naturally occurring flavolignan, has well known anti-cancer properties in several cancer cells, such as prostate cancer, cervical carcinoma and pancreatic cancer. However, the effects of Anthricin are currently unknown in oral cancer. We examined the anticancer effect and mechanism of action of Anthricin in human FaDu hypopharyngeal squamous carcinoma cells. Our data showed that Anthricin inhibits cell viability in a dose- and time-dependent manner ($IC_{50}$ 50 nM) in the MTT assay and Live & Dead assay. In addition, Anthricin treated FaDu cells showed marked apoptosis by DAPI stain and FACS. Furthermore, Anthricin activates anti-apoptotic factors such as caspase-3, -9 and poly (ADP-ribose) polymerase (PARP), suggesting that caspase-mediated pathways are involved in Anthricin- induced apoptosis. Anthricin treatment also leads to accumulation of the pro-apoptotic factor Bax, followed by inhibition of cell growth. Taken together, these results indicate that Anthricn-induced cell death of human FaDu hypopharyngeal squamous carcinoma cells is mediated by mitochondrial-dependent apoptotic pathway. In summary, our findings provide a framework for further exploration on Anthricin as a novel chemotherapeutic drug for human oral cancer.

• KSBB Journal
• /
• v.28 no.5
• /
• pp.303-309
• /
• 2013

The extract from Lysimachia foenum-graecum (LFE) has been known to possess various instructive characters including anti-oxidant, anti-obesity, fungicidal activities. However, the accurate mechanism of those effects of LFE is not well known. In that respect, we evaluated the apoptotic effect and anti-cancer efficacy of extracts of LFE in MCF-7 breast cancer cells. In this study, we hypothesized that LFE may exert cancer cell apoptosis through regulating p53 and mitochondria-mediated apoptotic proteins. And this substance can generate ROS to cause free radical-induced apoptosis. Accordingly, the generation of ROS by LFE triggers the activation of p53 which are accompanied by pro-apoptotic protein activation and suppression of pro-survival proteins. We determined with MTT assay, flow cytometry for detection of intracellular ROS and Annexin V-PI staining, Western blotting. Consequently, our researches demonstrated that the treatment of LFE to breast cancer cells resulted in an activation of p53, Puma, Bax, cleaved-PARP and an inhibition of Bcl-2 expressions.