A herbal formula, SYKT, reverses doxorubicin‑induced myelosuppression and cardiotoxicity by inhibiting ROS‑mediated apoptosis

Chen,Ting; Shen,Hong‑Mei; Deng,Zhi‑Yong; Yang,Zuo‑Zhang; Zhao,Rui‑Lian; Wang,Li; Feng,Zhi‑Ping; Liu,Chao; Li,Wen‑Hui; Liu,Zhi‑Jie

doi:10.3892/mmr.2017.6272

A herbal formula, SYKT, reverses doxorubicin‑induced myelosuppression and cardiotoxicity by inhibiting ROS‑mediated apoptosis

Authors:
- Ting Chen
- Hong‑Mei Shen
- Zhi‑Yong Deng
- Zuo‑Zhang Yang
- Rui‑Lian Zhao
- Li Wang
- Zhi‑Ping Feng
- Chao Liu
- Wen‑Hui Li
- Zhi‑Jie Liu
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Affiliations: Department of Nuclear Medicine, Tumor Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical College, Kunming, Yunnan 650118, P.R. China, Department of Combination of Chinese Traditional and Western Medicine, Tumor Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical College, Kunming, Yunnan 650118, P.R. China, Department of Orthopaedics, Tumor Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical College, Kunming, Yunnan 650118, P.R. China, The Institute of Molecular and Clinical Medicine of Kunming Medical College, Kunming, Yunnan 650500, P.R. China, Department of Radiotherapy, Tumor Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical College, Kunming, Yunnan 650118, P.R. China
Published online on: March 1, 2017 https://doi.org/10.3892/mmr.2017.6272
Pages: 2057-2066
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Doxorubicin (DOX) is an antineoplastic drug widely used for the treatment of various types of cancer; however, it can induce severe side effects, such as myelosuppression and cardiotoxicity. Sanyang Xuedai (SYKT) is a natural medicine originating from an ancient prescription of the Dai nationality in Southwest China. With eight Chinese herbal medicines, including sanguis draconis, radix et rhizoma notoginseng, radix et rhizoma glycyrrhizae and radix angelicae sinensis as the primary ingredients, SYKT has been reported to possess numerous biological functions. The present study investigated whether SYKT can confer protection against DOX‑induced myelosuppression and cardiotoxicity, and explored the potential mechanism involved. Mice were treated with DOX, SYKT or a combination of the two; hematopoietic functions were assessed by measuring the number of peripheral blood cells, cluster of differentiation CD34+/CD44+ bone marrow cells and apoptotic cells. Myocardial enzymes, including aspartate aminotransferase, lactate dehydrogenase, creatine kinase (CK) and its isoform CK‑MB, were assessed using a biochemical analyzer. The apoptotic rate of cardiomyocytes was assessed using flow cytometry. Histopathological analysis was conducted using hematoxylin‑eosin staining. Intracellular reactive oxygen species (ROS) production was evaluated using a dichlorofluorescein intensity assay. The mice treated with DOX exhibited a reduced survival rate, reduced peripheral blood and CD34+/CD44+ cell counts, elevated myocardial enzymes and apoptotic indices in bone marrow cells and cardiomyocytes, all of which were effectively prevented by SYKT co‑administration. Furthermore, bone marrow cells and myocytes from mice treated with DOX demonstrated increased dichlorofluorescein intensity, which was attenuated by SYKT. Notably, SYKT did not interfere with the effects of DOX on tumor volume or the induction of tumor cell apoptosis in tumor‑bearing mice. The present study indicated that SYKT may counteract DOX‑induced myelosuppression and cardiotoxicity through inhibiting ROS‑mediated apoptosis. These findings suggested that SYKT may have potential as a means to counteract the potentially fatal hematopoietic and cardiac complications associated with DOX treatment.

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