• Title/Summary/Keyword: caspase-8

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Momordica cochinchinensis Aril Extract Induced Apoptosis in Human MCF-7 Breast Cancer Cells

  • Petchsak, Phuchong;Sripanidkulchai, Bungorn
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.13
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    • pp.5507-5513
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    • 2015
  • Momordica cochinchinensis Spreng (MC) has been used in traditional medicine due to its high carotenoid content. The objective of this study was to investigate mechanisms underlying apoptotic effects of MC on human MCF-7 breast cancer cells. A lycopene-enriched aril extract of MC (AE) showed cytotoxicity and antiestrogenicity to MCF-7 cells. On DAPI staining, AE induced cell shrinkage and chromatin condensation were evident. With flow cytometric analysis, AE increased the percentage of cells in an early apoptosis stage when compared with the control group. RT-PCR analysis showed AE to significantly increase the expression of the proapoptotic bax gene without effect on expression of the anti-apoptotic bcl-2 gene. Moreover, AE enhanced caspase 6, 8 and 9 activity. Taken together, we conclude that AE of MC fruit has anticancer effects on human MCF-7 breast cancer cells by induction of cell apoptosis via both intrinsic and extrinsic pathways of signaling.

Targeted Silencing of Inhibitors of Apoptosis Proteins with siRNAs: A Potential Anti-cancer Strategy for Hepatocellular Carcinoma

  • Li, Gang;Chang, Hong;Zhai, Yun-Peng;Xu, Wei
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.4943-4952
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    • 2013
  • Hepatocellular carcinoma (HCC) is one of the most common malignancies, with a very poor prognosis. Despite significant improvements in diagnosis and treatment in recent years, the long-term therapeutic efficacy is poor, partially due to tumor metastasis, tecurrence, and resistance to chemo-or radio-therapy. Recently, it was found that a major feature of tumors is a combination of unrestrained cell proliferation and impaired apoptosis. There are now 8 recogized members of the IAP-family: NAIP, c-IAP1, c-IAP2, XIAP, Survivin, Bruce, Livin and ILP-2. There proteins all contribute to ingibition of apoptosis, and provide new potential avenues of cancer treatment. As a powerful tool to suppress gene expression in mammalian cells, RNAi species for inhibiting IAP genes cab be directed against cancers. This review will provide a brief introduction to recent developments of the application IAP-siRNA in tumor studies, with the aim of inspiring future treatment of HCC.

Inhibition of Cell Proliferation and Induction of Apoptosis by Methanolic Extract of Aconiti Tuber in Human Renal Cell Carcinoma Cells (부자의 메탄올 추출물에 의한 신세포암의 증식억제 및 세포사멸 유도)

  • Kim, Jong-Hwan;Choi, Yung-Hyun;Hwang, Won-Deuk
    • The Journal of Internal Korean Medicine
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    • v.29 no.1
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    • pp.42-66
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    • 2008
  • Aconiti Tuber is a traditional medicinal plant generally used in Oriental medicine therapy. In this study, we investigated the biochemical mechanisms of anti-proliferative effects by the methanol extract of Aconiti tuber (MEBJ) in Caki-1 human renal cell carcinoma cells. It was found that MEBJ could inhibit, in a dose-dependent manner, cell growth which was associated with apoptotic cell death such as formation of apoptotic bodies, DNA fragmentation and increased populations of apoptotic-sub G1 phase. Apoptosis of Caki-1 cells by MEBJ was associated with an up-regulation of pro-apoptotic Bax expression, and a down-regulation of anti-apoptotic Bcl-2 in a dose-dependent manner; however, the levels of IAP family were not affected. MEBJ treatment also induced the proteolytic activation of caspase-3 and -8, and a inhibition of poly(ADP-ribose) polymerase (PARP) and $PLC{\gamma}1$ protein. Furthermore, MEBJ treatment caused a dose-dependent inhibition of iNOS and cyclooxygenase-2 (Cox-2). Though further studies will be needed to identify the active compounds that confer the anti-cancer activity of MEBJ, the present findings provide important new insights into the possible molecular mechanisms of the apoptotic activity of MEBJ in cancer cells.

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Apoptosis Induction of MCF-7 Human Breast Carcinoma Cells by Butein (Butein에 의한 MCF-7 유방암 세포의 세포사멸에 의한 항암 효과)

  • Song, Ba-Da;Kim, Sun-Rye;Kim, Sung-Hun;Shin, Yong-Cheol;Ko, Seong-Gyu
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.3
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    • pp.385-389
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    • 2010
  • Butein(3,4,2',4-tetrahydroxychalcone) has been reported anticancer effects in several cancer type, which is prostate, bladder cancer but breast cancer is not. This study was to investigate the antiproliferative effects by butein(3,4,2',4-tetrahydroxychalcone) in MCF-7 human breast carcinoma cells. We invastigated the effects of dose-dependently cell growth inhibition by butein, which could be proved by WST-1 assay. Also, flow cytometry analysis was butein increase percentage of subG1 phase. As well as, butein induces apoptosis through the expression of caspase-8,-3 and poly(ADP-ribose) polymerase(PARP) activation but not in DMSO treated cells. Taken together, this results suggest that butein induced MCF-7 apoptosis through extrinsic pathway and thus may have potential tumor suppressor in breast cancer.

Effect of Achyrantis Radixs and Ultrasound in Osteoarthritis Rats Articular Cartilage (우슬과 초음파가 퇴행성관절염 백서의 관절 연골에 미치는 영향)

  • Kim, Eun-Jung;Chung, Hun-Woo;Kim, Gye-Yeop
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.2
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    • pp.390-396
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    • 2008
  • Osteoarthritis(OA) diseases are characterized by joint pain, tenderness, limitation of movement, crepitus, occasional effusion, and variable degrees of inflammation without systemic effects. We investigated the effects of Achyrantis radixs cream treatment and low intensity ultrasound in monosodium iodoacetate(MIA) induced experimental osteoarthritis rat. Sprague-Dawley 40 rats of 7-8 weeks, weight $250\;{\pm}\;50$ g were divided into four groups including the control group and ostoarthritis group(30 rats). Histopathological examination, Mankin's score, and immunohistochemical were performed. Histological findings in control group that are similar to those observed in human osteoarthritis, such as disorganization of chondrocytes, erosion and fibrillation of cartilage surface, and subchondral bone exposure. Safranin O-fast green staining revealed that marked diffuse reduction of proteoglycans and chondrocyte treated with MIA. The Mankin's score were closely correlated to the grade of histological findings. The level of Bax and caspase-3 expression decreased experimental groups. This study shows that a Acyranthes Radix cream treatment and low intensity ultrasound exerts a beneficial influence on the severity of chondral lesion in osteoarthritis rats. This treatments could related to a reduced level of chondrocyte apoptosis through anti-apoptotoc capacities of MIA-induced apoptotic protein overexpression.

(E)-2-Methoxy-4-(3-(4-Methoxyphenyl)Prop-1-en-1-yl)Phenol Induces Apoptosis in HeLa Cervical Cancer Cells via the Extrinsic Apoptotic Pathway

  • Park, Chan-Woo;Song, Yong-Seok;Lee, Hee Pom;Hong, Jin Tae;Yoon, Do-Young
    • Journal of Microbiology and Biotechnology
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    • v.27 no.7
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    • pp.1359-1366
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    • 2017
  • (E)-2-Methoxy-4-(3-(4-methoxyphenyl)prop-1-en-1-yl)phenol (MMPP), derived from butenal, is a recently synthesized Maillard reaction product. Owing to its novelty, little is known about the function of MMPP. In this study, we elucidated the effects of MMPP on apoptosis in cervical cancer by using the HeLa cervical cancer cell line, which is widely used in cancer research. We observed that MMPP was cytotoxic to HeLa cells and induced activation of caspase-3, -8, and -9, without affecting the expression of the viral oncogenes E6 and E7. In particular, the expression of the death receptors DR5 and FAS was significantly increased by MMPP treatment. There were no significant alterations of mitochondrial intrinsic factors. Taking all these results together, our findings show that MMPP primarily induces apoptosis in HeLa cervical cancer cells via the extrinsic apoptotic signaling pathway, accompanied by an enhanced expression of death receptors.

Induction of Oxidative Stress by Hexavalent Chromium in Human Bronchial Epithelial Cells (BEAS-2B) (배양 기관지 상피세포(BEAS-2B cells)에서 6가 크롬에 의한 산화적 스트레스)

  • Park, Eun-Jung;Kang, Mi-Sun;Kim, Dae-Seon;Park, Kwang-Sik
    • Environmental Analysis Health and Toxicology
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    • v.21 no.4 s.55
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    • pp.357-363
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    • 2006
  • Chromium compounds are widely used in diverse industries including pigment manufacturing, painting, metal plating and leather tanning. With the wide uses of chromium, various adverse effects of the compounds on the environment and human health have been reported. Among them, hexavalent chromium [Cr (VI)], which is a carcinogenic heavy metal, has been widely studies. Epidemiological investigations have shown that respiratory cancers had been found in workers who had been occupationally exposed to Cr (VI). In this study, cell toxicity and induction of reactive oxygen species (ROS) by Cr (VI) (1, 2, 4, $8{\mu}M$) in cultured human bronchial epithelial cells were investigated. Exposure of the cells to Cr (VI) led to cell death, ROS increase, and cytosolic caspase-3 activation. The ROS increase was related with the decreased level of GSH. Chromatin condensation and fragmentation were occurred by Cr (VI) when evaluated by DAPI staining or agarose gel electrophoresis of the extracted DNA. Expression of ROS related genes including glutathione S-transferase, heme oxygenase-1, metallothionein were significantly induced in Cr (VI) treated cells. This result suggests the toxicity in cultured cells by Cr (VI) was expressed through the apoptotic process with ROS induction.

Inhibitory Effect of Bee Venom Toxin on Lung Cancer NCI H460 Cells Growth Through Induction of Apoptosis via Death Receptor Expressions

  • Hur, Keun Young;Song, Ho Sueb
    • Journal of Acupuncture Research
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    • v.31 no.1
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    • pp.121-130
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    • 2014
  • Objectives : I investigated whether bee venom inhibit cell growth through enhancement of death receptor expressions in the human lung cancer cells, NCI-H460. Methods : Bee venom(1-5 ${\mu}g/ml$) inhibited the growth of NCI-H460 lung cancer cells by the induction of apoptotic cell death in a dose dependent manner. Results : Consistent with apoptotic cell death, expression of TNF-R1, TNF-R2, FAS, death receptors(DR) 3, 4, 5 and 6 was increased in the cells. Expression of DR downstream pro-apoptotic proteins including Caspase-8, -3, -9 was upregulated and Bax was concomitantly overwhelmed the expression of Bcl-2. NF-kB were inhibited by treatment with bee venom in NCI-H460 cells through TNF response change led by TNF-R1 and TNF-R2. Conclusions : These results suggest that bee venom should exert anti-tumor effect through induction of apoptotic cell death in NCI-H460 human lung cancer cells via enhancement of death receptor expression, and that bee venom could be a promising agent for preventing and treating lung cancer.

Stearoyl-CoA desaturase induces lipogenic gene expression in prostate cancer cells and inhibits ceramide-induced cell death

  • Kim, Seung-Jin;Kim, Eung-Seok
    • Animal cells and systems
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    • v.15 no.1
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    • pp.1-8
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    • 2011
  • Perturbation of metabolism with increased expression of lipogenic enzymes is a common characteristic of human cancers, including prostate cancer. In the present work the overexpression of stearoyl-CoA desaturase (SCD) in LNCaP cells led to increased mRNA levels of fatty acid synthase (FAS) and acetyl-CoA-carboxylase-a, whereas micro RNA-mediated silencing of SCD inhibited the expression of these lipogenic genes in LNCaP cells. Treatment with the FAS-specific inhibitor cerulenin inhibited SCD induction of LNCaP cell proliferation. In addition, a transient transfection assay revealed the capability of cerulenin to suppress SCD and dihydrotestosterone induction of androgen receptor transcriptional activity. Furthermore, overexpression of SCD in LNCaP cells produced marked resistance to ceramide-induced cell death with reduced poly(ADP-ribose) polymerase (PARP) cleavage. In contrast, silencing of SCD expression increased Bax protein in LNCaP cells. Furthermore, addition of ceramide to SCD knockdown LNCaP cells increased cell death and caspase-3 activity with drastic increase of PARP cleavage. Together, the data indicate that SCD may provide resistance of prostate cancer cells to ceramide-induced cell death.

Combination Therapy of Lactobacillus plantarum Supernatant and 5-Fluouracil Increases Chemosensitivity in Colorectal Cancer Cells

  • An, JaeJin;Ha, Eun-Mi
    • Journal of Microbiology and Biotechnology
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    • v.26 no.8
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    • pp.1490-1503
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    • 2016
  • Colorectal cancer (CRC) is the third most common cancer in the world. Although 5-fluorouracil (5-FU) is the representative chemotherapy drug for colorectal cancer, it has therapeutic limits due to its chemoresistant characteristics. Colorectal cancer cells can develop into cancer stem cells (CSCs) with self-renewal potential, thereby causing malignant tumors. The human gastrointestinal tract contains a complex gut microbiota that is essential for the host's homeostasis. Recently, many studies have reported correlations between gut flora and the onset, progression, and treatment of CRC. The present study confirms that the most representative symbiotic bacteria in humans, Lactobacillus plantarum (LP) supernatant (SN), selectively inhibit the characteristics of 5-FU-resistant colorectal cancer cells (HT-29 and HCT-116). LP SN inhibited the expression of the specific markers CD44, 133, 166, and ALDH1 of CSCs. The combination therapy of LP SN and 5-FU inhibited the survival of CRCs and led to cell death by inducing caspase-3 activity. The combination therapy of LP SN and 5-FU induced an anticancer mechanism by inactivating the Wnt/β-catenin signaling of chemoresistant CRC cells, and reducing the formation and size of colonospheres. In conclusion, our results show that LP SN can enhance the therapeutic effect of 5-FU for colon cancer, and reduce colorectal cancer stem-like cells by reversing the development of resistance to anticancer drugs. This implies that probiotic substances may be useful therapeutic alternatives as biotherapeutics for chemoresistant CRC.