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Chemopreventive Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
In vitro studies have shown that matrine can inhibit a number of tumor cell types (e.g., hepatoma G2 and gastric cancer SGC-7901) through G1 cell-cycle arrest, apoptosis, and autophagy. In in vivo experiments in BALB/c mice, it has been shown to inhibit tumors grown from BxPC-3, H22, 4T1, and MNNG/HOS cells. The exact mechanism of action is unclear, although it has been shown to modulate a number of proteins involved in apoptosis or cell proliferation such as Bcl-2, Bax, E2F-1, Fas, and Fas-L. It has also been shown to inhibit cancer cell invasion through, in part, modulation of the NF-κB signaling pathway, and inhibition of MMP-2 and MMP-9 expression.
Introduction to Bioresponsive Polymers
Published in Deepa H. Patel, Bioresponsive Polymers, 2020
Deepa H. Patel, Drashti Pathak, Neelang Trivedi
Hypoxia in tumors contributes to overall tumor progression by assisting in epithelial-to-mesenchymal transition, angiogenesis, and metastasis of cancer. In this study, we have synthesized a hypoxia-responsive, diblock copolymer poly(lactic acid)-azobenzene-poly(ethylene glycol), which self-assembles to form polymersomes in an aqueous medium. The polymersomes did not release any encapsulated contents for 50 min under normoxic conditions. However, under hypoxia, 90% of the encapsulated dye was released in 50 min. The polymersomes encapsulated the combination of anticancer drugs gemcitabine and erlotinib with entrapment efficiency of 40% and 28%, respectively. We used three-dimensional spheroid cultures of pancreatic cancer cells BxPC-3 to demonstrate the hypoxia-mediated release of the drugs from the polymersomes. The vesicles were nontoxic. However, a significant decrease in cell viability was observed in hypoxic spheroidal cultures of BxPC-3 cells in the presence of drug encapsulated polymersomes. These polymersomes have the potential for future applications in imaging and treatment of hypoxic tumors [97].
Involvement of Dopamine with Various Cancers
Published in Nira Ben-Jonathan, Dopamine, 2020
Microarrays with 195 pancreatic ductal adenocarcinomas (PDACs) and 41 non-tumor pancreatic tissues were used for gene expression profile analysis [66]. Another set of 152 samples (40 non-tumor pancreatic tissues, 63 PDAC sections, and 49 chronic pancreatitis samples) was used for tissue microarray analysis. The D2R protein was much higher in PDACs than in non-tumor tissues. Five pancreatic cancer cell lines at various degrees of differentiation were then used: moderately differentiated BxPC-3 cells, poorly differentiated Panc-1 and MiaPaCa-2, and well-differentiated Capan-1 and CFPAC-1 cells; human dermal fibroblasts served as controls. Knockdown of DRD2 by RNAi or its inhibition with pimozide and haloperidol reduced cell proliferation and migration and induced apoptosis. In orthotopically transplanted pancreatic tumor cells, DRD2 knockdown or haloperidol administration reduced tumor growth and metastases. The authors concluded that D2R antagonists, routinely used for management of schizophrenia, should be tested in patients with pancreatic cancer.
Celastrol-conjugated chitosan oligosaccharide for the treatment of pancreatic cancer
Published in Drug Delivery, 2022
Xiaohu Zeng, Xin Zhu, Qikang Tian, Xiaoke Tan, Ning Sun, Min Yan, Junwei Zhao, Xiangxiang Wu, Ruiqin Li, Zhenqiang Zhang, Huahui Zeng
Celastrol was obtained from Xi’an Haoxuan Biotechnology Co. Ltd. (Shanxi, China). Chitosan oligosaccharide (CSO, 1–3 kDa) was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd. (Shanghai, China). Other chemical reagents were purchased from commercial suppliers without purification for the next experiment. Human pancreatic cancer cells (BxPC-3) and hepatic cells (HL7702) were obtained from the American Type Culture Collection (VA, USA) and were cultured according to the instructions. BALB/c (nude) mice (20–22 g) were obtained from the Huaxing laboratory animal farm (Production license NO: 20190002, Zhengzhou, China). All animal studies were performed in accordance with the guidelines of the Institute’s Animal Care and Use Committee in Henan University of Chinese Medicine.
A Marine Carotenoid of Fucoxanthinol Accelerates the Growth of Human Pancreatic Cancer PANC-1 Cells
Published in Nutrition and Cancer, 2022
Masaru Terasaki, Shouta Takahashi, Ryuta Nishimura, Atsuhito Kubota, Hiroyuki Kojima, Tohru Ohta, Junichi Hamada, Yasuhiro Kuramitsu, Hayato Maeda, Kazuo Miyashita, Mami Takahashi, Michihiro Mutoh
The growth of PANC-1 cells was significantly increased, whereas MIA PaCa-2 and DLD-1 cells were significantly decreased, by the FxOH treatment in a dose-dependent manner. The percentages of cell growth (control 100%) were as follows: 1.0 μM FxOH, 114.2 ± 1.0%; 5.0 μM FxOH, 134.8 ± 2.2% in PANC-1 cells; 1.0 μM FxOH, 97.3 ± 1.1%; 5.0 μM FxOH, 87.1 ± 1.1% in MIA PaCa-2 cells; 1.0 μM FxOH, 68.7 ± 0.7%; 5.0 μM FxOH, 68.2 ± 1.4% in DLD-1 cells. The growth of BxPC-3 cells was slightly decreased by the FxOH treatment (Figure 1B). The treatment with 5.0 μM FxOH promoted apoptosis-like chromatin condensation and nuclear fragmentation and significantly increased the percentage of Sub-G1 (control cells, 2.4 ± 0.1% and FxOH-treated cells, 9.3 ± 1.0%) in DLD-1 cells, but not in PANC-1 cells (Figure 2A and B). The percentage of DLD-1 cells in each phase of the cell cycle was significantly altered by the treatment with 5.0 μM FxOH as follows: G0/G1 phase, control cells, 49.9 ± 0.3% and FxOH-treated cells, 58.4 ± 1.2%; S phase, control cells, 19.5 ± 0.7% and FxOH-treated cells, 9.0 ± 1.2%. The percentage of PANC-1 cells in each phase of the cell cycle did not significantly differ between control and FxOH-treated cells (Figure 2C).
In vivo antitumor effects of carboxymethyl chitosan-conjugated triptolide after oral administration
Published in Drug Delivery, 2020
Huahui Zeng, Xin Zhu, Qikang Tian, Yinyin Yan, Lan Zhang, Min Yan, Ruiqin Li, Xiaofang Li, Guoqiang Wang, Jinlian Ma, Yufang Su, Xiangbo Zhang, Linyu Ma, Zhenqiang Zhang, Xiangxiang Wu
TP was purchased from Xi’an Haoxuan Biotechnology Co. Ltd. (Shanxi, China). CC was obtained from Aladdin (Beijing, China) and was further purified by dialysis. Hyclone fetal bovine serum, bovine serum albumin (BSA) and Dulbecco’s modified Eagle’s medium (DMEM) were supplied by Gibco Co. Ltd. (USA). Freund’s complete adjuvant was from Sigma (USA). Human pancreatic cancer cells (BxPC-3) and hepatic cells (HL7702) were from the American Type Culture Collection (VA, USA). All other reagents and solvents were purchased from commercial suppliers with the analytical grade. BALB/c mice (20-22 g) were purchased from the Huaxing laboratory animal farm (Production license NO: 20190002, Zhengzhou, China). The animals were allowed to acclimatize for seven days in environmentally controlled quarters (25 ± 1 °C, 12 h light-dark cycle), provided with water and food. All animal studies were performed under a protocol approved by the Institute’s Animal Care and Use Committee.