title: Supercritical-Carbon Dioxide Fluid Extract from Chrysanthemum indicum Enhances Anti-Tumor Effect and Reduces Toxicity of Bleomycin in Tumor-Bearing Mice.
abstract: Bleomycin (BLM), a family of anti-tumor drugs, was reported to exhibit severe side effects limiting its usage in clinical treatment. Therefore, finding adjuvants that enhance the anti-tumor effect and reduce the detrimental effect of BLM is a prerequisite.Chrysanthemum indicum, an edible flower, possesses abundant bioactivities; the supercritical-carbon dioxide fluid extract from flowers and buds ofC. indicum(CISCFE) have strong anti-inflammatory, anti-oxidant, and lung protective effects. However, the role of CISCFEcombined with BLM treatment on tumor-bearing mice remains unclear. The present study aimed to investigate the potential synergistic effect and the underlying mechanism of CISCFEcombined with BLM in the treatment of hepatoma 22 (H22) tumor-bearing mice. The results suggested that the oral administration of CISCFEcombined with BLM could markedly prolong the life span, attenuate the BLM-induced pulmonary fibrosis, suppress the production of pro-inflammatory cytokines (interleukin-6), tumor necrosis factor-α, activities of myeloperoxidase, and malondiadehyde. Moreover, CISCFEcombined with BLM promoted the ascites cell apoptosis, the activities of caspases 3 and 8, and up-regulated the protein expression of p53 and down-regulated the transforming growth factor-β1 by activating the gene expression of miR-29b. Taken together, these results indicated that CISCFEcould enhance the anti-cancer activity of BLM and reduce the BLM-induced pulmonary injury in H22 tumor-bearing mice, rendering it as a potential adjuvant drug with chemotherapy after further investigation in the future.
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. yanghongmei326@gmail.com.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Yang
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. yuhongl0822@gmail.com.
authors.forename: Chao-Yue
authors.initials: CY
authors.lastname: Sun
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. xing623853793@gmail.com.
authors.forename: Jia-Li
authors.initials: JL
authors.lastname: Liang
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. xulieqiang123@gmail.com.
authors.forename: Lie-Qiang
authors.initials: LQ
authors.lastname: Xu
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. Lauyh0822@gmail.com.
authors.forename: Zhen-Biao
authors.initials: ZB
authors.lastname: Zhang
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. zhuojiany38193@gmail.com.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Luo
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. chenhanbin999@gmail.com.
authors.forename: Han-Bin
authors.initials: HB
authors.lastname: Chen
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. jakin3305@gmail.com.
authors.forename: Yong-Zhong
authors.initials: YZ
authors.lastname: Huang
authors.affiliation: Guangdong New South Artepharm, Co., Ltd., Guangzhou 510006, China. l1393318376@gmail.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of McLean Hospital, Harvard Medical School, Belmont, CA 02478-9106, USA. ywlee228@gmail.com.
authors.forename: David Yue-Wei
authors.initials: DY
authors.lastname: Lee
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. yuanjie@gzucm.edu.cn.|Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan 523000, China. yuanjie@gzucm.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. liyucui@gzucm.edu.cn.
authors.forename: Yu-Cui
authors.initials: YC
authors.lastname: Li
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001761:Bleomycin / Q000009:adverse effects / Q000494:pharmacology*; D002245:Carbon Dioxide; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D031202:Chrysanthemum / Q000737:chemistry*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004357:Drug Synergism; D005355:Fibrosis; D059625:Liquid-Liquid Extraction / Q000379:methods; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D016207:Cytokines; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D010936:Plant Extracts; D053773:Transforming Growth Factor beta1; D016159:Tumor Suppressor Protein p53; D001761:Bleomycin; D002245:Carbon Dioxide; D053148:Caspase 3; D053181:Caspase 8
keywords: BLM; anti-tumor effect; pulmonary fibrosis; supercritical-carbon dioxide fluid of C. indicum (CISCFE); synergism effect