• 한방안이비인후피부과학회지
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• 제27권4호
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• pp.158-176
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• 2014

Purpose : The purpose of this study is to investigate the effect of ARTEMISIAE CAPILLARIS HERBA and COPTIDIS RHIZOMA Extracts on cell death in pancreatic cancer cells. Method : Human-derived pancreatic cancer cell line, MIA PaCa-2 cells were treated by Prescription A with various concentrations and the cytotoxicity was determined by MTT assay. To investigate the effects of Prescription A on pancreatic cancer cells, the staining of Annexin V/PI, cell cycle arrest, nuclear chromatin condensation and the production of reactive oxygen species (ROS) were examined. The effect of Prescription A's effective components, ARTEMISIAE CAPILLARIS HERBA and COPTIDIS RHIZOMA Extracts on cell death were also observed. Results : The viability of MIA PaCa-2 cells treated with Prescription A were decreased in a dose dependent manner. Prescription A induced cell death in MIA PaCa-2 cells as shown by result of Annexin V/PI double staining, chromatin condensation and cell cycle arrest. In addition, production of ROS was increased by Prescription A treatment, suggesting that ROS induced by Prescription A mediated cell death. Furthermore, Prescription A's effective components, ARTEMISIAE CAPILLARIS HERBA and COPTIDIS RHIZOMA Extracts were also induced apoptosis of MIA PaCa-2 cells through ROS production. Conclusion : These results suggest that Prescription A's effective components, ARTEMISIAE CAPILLARIS HERBA and COPTIDIS RHIZOMA Extracts induced death of MIA PaCa-2 through ROS production.

• 동의생리병리학회지
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• 제27권2호
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• pp.202-211
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• 2013

The purpose of this study is to investigate the apoptotic effect of Phellodendri Cortex water extract (PCWE) on pancreatic cancer cells and to find out the regulating mechanisms. Human-derived pancreatic cancer cell line, MIA PaCa-2 cells were treated by PCWE with various concentrations and the cytotoxicity was determined by MTT assay. The activation of Annexin V, DNA fragmentation, cell cycle arrest and caspase activation were observed to investigate the role of PCWE in pancreatic cancer cells. Also, to find out the regulating mechanisms, we examined the ROS production. The treatment of PCWE induced the cell death in both concentration and time dependent manner. The treatment of PCWE also increased the expression of Annexin V, DNA fragmentation, cell cycle arrest, and cleavage of caspase, which means cell-death PCWE induced was apoptosis but not necrosis. The ROS production was increased by PCWE treatment and the blockade of ROS inhibited the PCWE-induced cell death. These results could suggest that PCWE induced apoptosis via ROS release in pancreatic cancer cell.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1793-1797
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• 2012

Objective: To analyze the capacity of neurotrophic artemin to promote the motility and invasiveness of MIA PaCa-2 pancreatic cancer cells. Methods: MIA PaCa-2 was cultured in vitro and studied using transwell chambers for motility and invasiveness on treatment with different concentrations of aArtemin or its receptor $GFR{\alpha}3$ were also determined. Expression of matrix metalloproteinase-2 (MMP-2) and epithelial cadherin (E-cadherin) was quantified using RT-PCR and Western blotting. Results: MIA PaCa-2 pancreatic cancer cell motility and invasiveness was significantly increased with artemin and its receptor $GFR{\alpha}3$ with dose dependence (P<0.01). MMP-2 production was also significantly increased (t = 6.35, t = 7.32), while E-cadherin was significantly lowered (t = 4.27, t = 5.61) (P <0.01). Conclusion: Artemin and its receptor $GFR{\alpha}3$ can promote pancreatic cancer cell motility and invasiveness and contribute to aggressive behavior. The mechanism may be related to increased expression of MMP-2 molecule and down-regulation of E-cadherin expression.

• Natural Product Sciences
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• 제25권4호
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• pp.298-303
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• 2019

This study investigated the cytotoxic effects and mechanism of action of asiatic acid in pancreatic cancer cell lines. First, we confirmed the cell viability of MIA PaCa-2 and PANC-1 cells after asiatic acid administration for 48 and 72 h. The viability of MIA PaCa-2 and PANC-1 cells decreased in a dose-dependent manner following asiatic acid administration. To investigate the underlying mechanism, we performed a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, annexin V assay, and western blotting. Asiatic acid induced apoptosis and autophagy through activation of AMP-activated protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) in MIA PaCa-2 cells. Finally, the expression of miR-17 and miR-21, known as oncogenes in pancreatic cancer, was decreased by asiatic acid. These results indicate that asiatic acid has potential as a new therapeutic agent against pancreatic cancer.

• Bulletin of the Korean Chemical Society
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• 제34권2호
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• pp.482-488
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• 2013

Two piperazine-containing 3,4-dihyroquinazolines (BK10007S/8S) have been synthesized, based on our previous work on the synthesis and antitumoral activity of 3,4-dihyroquinazolines. After evaluating them for T-type calcium channel blocking effect and in vitro anti-cancer effect, they were profiled for acute and repeat dose toxicity (40 mg/kg, 2 weeks) to BALB/c mice. BK10007S/8S were further in vivo evaluated against human pancreatic MIA PaCa-2 carcinoma in $BALB/c^{nu/nu}$ nude mice, which exhibited 54 and 61% tumor growth inhibition through 57-day oral administration of 2 mg/kg of body weight, respectively.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5905-5910
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• 2013

Background: To investigate the preventive and therapeutic potential of garlic oil on human pancreatic carcinoma cells. Methods: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was performed to study the effects of garlic oil on three human pancreatic cancer cell lines, AsPC-1, Mia PaCa-2 and PANC-1. Cell cycle progression and apoptosis were detected by flow cytometry (FCM), staining with PI and annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI), respectively. Morphologic changes of pancreatic cancer cells were observed under transmission electron microscopy (TEM) after treatment with garlic oil at low inhibitory concentrations ($2.5{\mu}M$ and $10{\mu}M$) for 24 hours. Results: Proliferation of the AsPC-1, PANC-1, and Mia PaCa-2 cells was obviously inhibited in the first 24 hours with the MTT assay. The inhibition effect was more significant after 48 hours. When cells were exposed to garlic oil at higher concentrations, an early change of the apoptotic tendency was detected by FCM and TEM. Conclusion: Garlic oil could inhibit the proliferation of AsPC-1, PANC-1, and Mia PaCa-2 cells in this study. Moreover, due to programmed cell death, cell cycle arrest, or both, pro-apoptosis effects on AsPC-1 cells were induced by garlic oil in a dose and time dependent manner in vitro.

• Biomolecules & Therapeutics
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• 제25권6호
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• pp.609-617
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• 2017

Pancreatic cancer is one of the most lethal and aggressive cancers in the world. However, no effective treatment is currently available for pancreatic cancer. The objective of this study was to determine the anti-pancreatic cancer effect of ${\alpha}$-mangostin (${\alpha}M$) and ${\gamma}$-mangostin (${\gamma}M$) extracted from the pericarp of Garcinia mangostana L.. Both ${\alpha}$M and ${\gamma}M$ reduced the viability of pancreatic cancer cells MIA PaCa-2 and PANC-1 in a dose-dependent manner. These compounds induced apoptosis by increasing c-PARP and c-Caspase 3 levels. They also induced autophagy by increasing levels of microtubule-associated protein 1A/1B light chain 3B (LC3II) in both cell lines while decreasing sequestosome 1 (p62) in MIA PaCa-2. Both ${\alpha}$M and ${\gamma}M$ induced autophagy through increasing phosphorylation levels of AMP-activated protein kinase (p-AMPK) and p38-mitogen activated protein kinase (p-p38) while decreasing phosphorylation level of mammalian target of rapamycin complex 1 (p-mTOR). Of various microRNAs (miRNA), miR-18a was found to be a putative regulatory miRNA for autophagy induced by ${\alpha}$M or ${\gamma}M$. In combination with gemcitabine, a compound frequently used in pancreatic cancer treatment, ${\alpha}$M and ${\gamma}M$ showed synergistic anti-cancer effects in MIA PaCa-2. Collectively, these results suggest that ${\alpha}$M and ${\gamma}M$ can induce apoptosis and autophagy in pancreatic cancer cells and that their anti-cancer effect is likely to be associated with miR-18a. In conclusion, ${\alpha}$M and ${\gamma}M$ might be used as a potential new therapy for pancreatic cancer.

• Animal cells and systems
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• 제6권2호
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• pp.167-170
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• 2002

The long terminal repeats (LTRs) of human endogenous retrovirus (HERV) have been found to be coexpressed with sequences of closely located genes. It has been suggested that the LTR elements have contributed to the structural change or genetic variation of human genome connected to various diseases and evolution. We examined the HERV-W LTR elements in various cancer cells (2F7, A43l , A549, HepG2, MIA-PaCa-2, PC-3, RT4, SiHa, U-937, and UO-31). Using genomic DNA from the cancer cells, we performed PCR amplification and identified twelve new HERV-W LTR elements. Those LTR elements showed a high degree of sequence similarity (88-99％) with HERV-W LTR (AF072500). A phylogenetic tree obtained by the neighbor-joining method revealed that HERV-W LTR elements could be mainly divided into two groups through evolutionary divergence. Three HERV-W LTR elements (RT4-2, A43l-1, and UO3l-2) belonged to Group 1, whereas nine LTR elements (2F7-2, A549-1, A549-3, HepG2-3, MP2-2, PC3-1, SiHa-8, SiHa-10, and U937-1) belonged to Group 11. Taken together, our new sequence data of the HERV-W LTR elements may contribute to an understanding of tissue-specific cancer by genomic instability of LTR integration.

• 대한한방내과학회지
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• 제40권1호
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• pp.70-88
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• 2019

Objective: This study investigated the trends in pancreatic cancer research on Korean medicine in order to establish a direction for further study. Methods: Pancreatic cancer research on Korean medicine was reviewed using databases such as OASIS, KoreanTK, KISS, RISS, KISTI, and NDSL. The search terms were "pancreatic cancer" "Korean medicine," and "herbal medicine." There was no restriction on publication dates, and the reviewed studies were analyzed according to the type of research. Results: Nineteen studies were reviewed. The numbers and types of research were as follows: 9 clinical studies including case reports, 2 review studies, and 8 in vitro studies; there was no in vivo study. Among the clinical research were 3 descriptive studies and 6 case reports. The baseline characteristics and quality of life of pancreatic cancer patients were analyzed in the descriptive studies. In the case reports, interventions such as herbal medicine, pharmacopuncture, and acupuncture were used. Research articles on the review of pancreatic cancer were titled "Preliminary Study for Development of Korean Medicine Clinical Practice Guideline for Pancreatic Cancer" and "Systemic Review on the Tumor Dormancy Therapy." Cell lines such as PANC-1, MIA PaCa-2, and AsPC-1 were used for in vitro studies. These studies have reported decreased cell viability, induced apoptosis, and changes in cancer-related gene expression. Conclusion: Through this review, we found that using Korean medicine for treating pancreatic cancer is applicable. However, due to overall limited the number of study, the benefit of Korean medicine for pancreatic cancer may be substantiated to a limited degree. Better methodological quality and large controlled trials are expected to further quantify the therapeutic effect of Korean medicine.

• Journal of Microbiology and Biotechnology
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• 제32권5호
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• pp.645-656
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• 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.