Preferential cytotoxicity of crude drugs used in Japanese Kampo medicines against human pancreatic cancer PANC-1 and PSN-1 cells
Preferential cytotoxicity of crude drugs used in Japanese Kampo medicines against human pancreatic cancer PANC-1 and PSN-1 cells
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日本汉方药中所用生药对人胰腺癌PANC-1和PSN-1细胞的优先细胞毒性
DOI：
10.1002/tkm2.1016
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Y. Tezuka
中科院分区：
文献类型：
--
作者：
S. Lee;D.F. Dibwe;F. Li;H. Morita;Y. Tezuka
目的胰腺癌是所有癌症中最具侵袭性的癌症，其全球死亡率极高，在最常见的癌症死亡原因中排名第七。为了鉴定抗胰腺癌药物，我们基于反紧缩策略筛选了24种汉方药中使用的生药的优先细胞毒性。方法通过比较正常培养基（DMEM）和营养剥夺培养基中对PANC-1和PSN-1人胰腺癌细胞的细胞毒性，确定优先细胞毒性。然后，对显示出有效活性的提取物进行溴化乙锭/吖啶橙（EB/AO）双染色检查其细胞死亡机制。 结果 在检查的 24 种提取物中，穿心莲提取物（穿心莲的地上部分）对两种细胞系具有最有效的优先细胞毒性，其浓度使 50% 的细胞在 NDM (PC50) 中优先死亡。 9.72μg/mL (PANC-1) 和 9.41μg/mL (PSN-1)，以及异豆提取物（左手香的地上部分）、黄柏皮层（黄柏树皮）、石松（石松孢子）和日本参（根） Panax japonicas）具有轻微的活性。对这些提取物处理的细胞进行 EB/AO 双重染色，异冬草、甘草和参参在营养饥饿下诱导细胞凋亡样细胞死亡，而黄柏和穿心莲则诱导坏死样细胞死亡。 Panacis japonici rhizoma，可用于治疗胰腺癌和/或作为抗胰腺癌药物的来源。
AimPancreatic cancer is the most aggressive cancer of all and has an exceptionally high global mortality rate, ranking seventh as the most frequent cause of cancer death. In order to identify an anti‐pancreatic cancer drug, we screened 24 crude drugs used in Kampo medicine for preferential cytotoxicity based on anti‐austerity strategy.MethodsPreferential cytotoxicity was determined by comparing the cytotoxicities against PANC‐1 and PSN‐1 human pancreatic cancer cells in normal medium (DMEM) and nutrient‐deprived medium. The extracts that showed potent activity were then examined for the mechanism of cell death on ethidium bromide/acridine orange (EB/AO) double staining.ResultsAmong the 24 extracts examined, extract of andrographis herba (aerial part ofAndrographis paniculata) had the most potent preferential cytotoxicity against both cell lines, with concentration at which 50% of cells died preferentially in NDM (PC50) of 9.72 µg/mL (PANC‐1) and 9.41 µg/mL (PSN‐1), and extracts of isodonis herba (aerial part ofPlectranthus japonicas), phellodendri cortex (bark ofPhellodendron amurense), licopodium (spore ofLycopodium clavatum), and panacis japonici rhizoma (radix ofPanax japonicas) had mild activity. On EB/AO double‐staining of cells treated by these extracts, isodonis herba, licopodium, and panacis japonici rhizoma induced apoptosis‐like cell death under nutrient starvation, whereas phellodendri cortex and andrographis herba induced necrosis‐like cell death.ConclusionThe crude drugs used in Japanese Kampo medicines, isodonis herba, phellodendri cortex, licopodium, andrographis herba, and panacis japonici rhizoma, could be used in the treatment of pancreatic cancer and/or as sources of anti‐pancreatic cancer drugs.