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Article: Multiple modulatory activities of Andrographis paniculata on immune responses and xenograft growth in esophageal cancer preclinical models

TitleMultiple modulatory activities of Andrographis paniculata on immune responses and xenograft growth in esophageal cancer preclinical models
Authors
KeywordsAndrographis paniculata
Anti-tumor
Esophageal cancer
Esophageal patient-derived xenografts
Immunomodulation
Multi-targeted
Issue Date2019
Citation
Phytomedicine, 2019, v. 60, article no. 152886 How to Cite?
AbstractBackground: Esophageal cancer (EC) is a malignant gastrointestinal cancer with high morbidity worldwide and is the fourth leading cause of cancer-related deaths in China. Even though surgery and/or chemotherapy/chemoradiation might achieve good therapeutic response, recurrence rate is high due to cancer metastasis. Hence, the use of alternative adjuvant treatments, such as herbal medicines, for metastatic EC remains a great desire of the patients. Our previous studies have demonstrated the anti-metastatic efficacy of hot water extract of Andrographis paniculata (APW) in human esophageal cancer cells and tumor-bearing nude mice. Purpose: In the present study, the immunomodulatory activities of APW were further evaluated in human peripheral blood mononuclear cells (PBMCs) and in a carcinogen-induced esophageal tumorigenesis model using immune-competent C57BL/6 mice. Besides, the inhibitory effects of APW on esophageal cancer cell line-based xenografts and patient-derived xenografts (PDX) were examined so as to illustrate the potential multi-targeted efficacies of APW in esophageal cancer in pre-clinical models. Results: In vitro results showed that APW could stimulate proliferation of PBMCs, as well as TNF-α and IFN-γproductions. In mice with 4-nitroquinoline 1-oxide-induced tumorigenesis, 21-day oral treatment with APW (1600 mg/kg) decreased the level of dysplasia in esophagus and significantly modulated the population of regulatory T cells. The cytokines productions by spleen lymphocytes of APW-treated mice were shifted towards normal resting state (i.e. unchallenged with carcinogen). Furthermore, APW treatment suppressed the growth of cell line-based xenografts by significantly increasing apoptosis in tumors, without causing severe body weight loss as chemotherapeutics did. Most importantly, the inhibitory effects of APW treatment on esophageal patient-derived xenografts growth were demonstrated for the first time. Besides, several diterpenes were detected in the plasma after oral administration of APW in mice, suggesting that multi-components of APW were bioavailable and might have contributed towards the varied pharmacological activities demonstrated in our studies. Conclusion: APW was shown to possess anti-tumor, anti-metastatic and immunomodulatory activities in esophageal cancer cell-based and animal models, including immunocompromised mice model and clinically relevant PDX model. Our findings illustrated the potential multi-targeted efficacies of APW in esophageal cancer management.
Persistent Identifierhttp://hdl.handle.net/10722/343279
ISSN
2023 Impact Factor: 6.7
2023 SCImago Journal Rankings: 1.267

 

DC FieldValueLanguage
dc.contributor.authorYue, Grace Gar Lee-
dc.contributor.authorLi, Lin-
dc.contributor.authorLee, Julia Kin Ming-
dc.contributor.authorKwok, Hin Fai-
dc.contributor.authorWong, Eric Chun Wai-
dc.contributor.authorLi, Mingyue-
dc.contributor.authorFung, Kwok Pui-
dc.contributor.authorYu, Jun-
dc.contributor.authorChan, Anthony Wing Hung-
dc.contributor.authorChiu, Philip Wai Yan-
dc.contributor.authorLau, Clara Bik San-
dc.date.accessioned2024-05-10T09:06:52Z-
dc.date.available2024-05-10T09:06:52Z-
dc.date.issued2019-
dc.identifier.citationPhytomedicine, 2019, v. 60, article no. 152886-
dc.identifier.issn0944-7113-
dc.identifier.urihttp://hdl.handle.net/10722/343279-
dc.description.abstractBackground: Esophageal cancer (EC) is a malignant gastrointestinal cancer with high morbidity worldwide and is the fourth leading cause of cancer-related deaths in China. Even though surgery and/or chemotherapy/chemoradiation might achieve good therapeutic response, recurrence rate is high due to cancer metastasis. Hence, the use of alternative adjuvant treatments, such as herbal medicines, for metastatic EC remains a great desire of the patients. Our previous studies have demonstrated the anti-metastatic efficacy of hot water extract of Andrographis paniculata (APW) in human esophageal cancer cells and tumor-bearing nude mice. Purpose: In the present study, the immunomodulatory activities of APW were further evaluated in human peripheral blood mononuclear cells (PBMCs) and in a carcinogen-induced esophageal tumorigenesis model using immune-competent C57BL/6 mice. Besides, the inhibitory effects of APW on esophageal cancer cell line-based xenografts and patient-derived xenografts (PDX) were examined so as to illustrate the potential multi-targeted efficacies of APW in esophageal cancer in pre-clinical models. Results: In vitro results showed that APW could stimulate proliferation of PBMCs, as well as TNF-α and IFN-γproductions. In mice with 4-nitroquinoline 1-oxide-induced tumorigenesis, 21-day oral treatment with APW (1600 mg/kg) decreased the level of dysplasia in esophagus and significantly modulated the population of regulatory T cells. The cytokines productions by spleen lymphocytes of APW-treated mice were shifted towards normal resting state (i.e. unchallenged with carcinogen). Furthermore, APW treatment suppressed the growth of cell line-based xenografts by significantly increasing apoptosis in tumors, without causing severe body weight loss as chemotherapeutics did. Most importantly, the inhibitory effects of APW treatment on esophageal patient-derived xenografts growth were demonstrated for the first time. Besides, several diterpenes were detected in the plasma after oral administration of APW in mice, suggesting that multi-components of APW were bioavailable and might have contributed towards the varied pharmacological activities demonstrated in our studies. Conclusion: APW was shown to possess anti-tumor, anti-metastatic and immunomodulatory activities in esophageal cancer cell-based and animal models, including immunocompromised mice model and clinically relevant PDX model. Our findings illustrated the potential multi-targeted efficacies of APW in esophageal cancer management.-
dc.languageeng-
dc.relation.ispartofPhytomedicine-
dc.subjectAndrographis paniculata-
dc.subjectAnti-tumor-
dc.subjectEsophageal cancer-
dc.subjectEsophageal patient-derived xenografts-
dc.subjectImmunomodulation-
dc.subjectMulti-targeted-
dc.titleMultiple modulatory activities of Andrographis paniculata on immune responses and xenograft growth in esophageal cancer preclinical models-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.phymed.2019.152886-
dc.identifier.pmid30910259-
dc.identifier.scopuseid_2-s2.0-85063296054-
dc.identifier.volume60-
dc.identifier.spagearticle no. 152886-
dc.identifier.epagearticle no. 152886-
dc.identifier.eissn1618-095X-

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