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Article: Turmeric Is Therapeutic in Vivo on Patient-Derived Colorectal Cancer Xenografts: Inhibition of Growth, Metastasis, and Tumor Recurrence

TitleTurmeric Is Therapeutic in Vivo on Patient-Derived Colorectal Cancer Xenografts: Inhibition of Growth, Metastasis, and Tumor Recurrence
Authors
Keywordscolorectal cancer
herbal medicines
network pharmacology
patient-derived xenografts
tumor recurrence
turmeric
Issue Date2021
Citation
Frontiers in Oncology, 2021, v. 10, article no. 574827 How to Cite?
AbstractColorectal cancer is the third most frequently diagnosed cancer worldwide. Clinically, chemotherapeutic agents such as FOLFOX are the mainstay of colorectal cancer treatment. However, the side effects including toxicity of FOLFOX stimulated the enthusiasm for developing adjuvants, which exhibit better safety profile. Turmeric extract (TE), which has been previously shown to suppress the growth of human and murine colon xenografts, was further demonstrated here for its inhibitory effects on colon cancer patient-derived xenografts (PDX). PDX models were successfully established from tissues of colon cancer patients and the PDX preserved the heterogeneous architecture through passages. NOD/SCID mice bearing PDX were treated either with TE or FOLFOX and differential responses toward these treatments were observed. The growth of PDX, metastasis and tumor recurrence in PDX-bearing mice were suppressed after TE treatments with 60% anti-tumor response rate and 83.3% anti-metastasis rate. Mechanistic studies showed that TE reduced tumor cell proliferation, induced cell apoptosis, inhibited metastasis via modulating multiple targets, such as molecules involved in Wnt and Src pathways, EMT and EGFR-related pathways. Nevertheless, FOLFOX treatments inhibited the PDX growth with sharp decreases of mice body weight and only mild anti-metastasis activities were observed. Furthermore, in order to have a better understanding of the underlying mechanisms, network pharmacology was utilized to predict potential targets and mechanism. In conclusion, the present study demonstrated for the first time that oral TE treatment was effective to suppress the growth of colon PDX and the recurrence of colon tumors in mice. The findings obtained from this clinically relevant PDX model would certainly provide valuable information for the potential clinical use of TE in colorectal cancer patients. The application of PDX model was well illustrated here as a good platform to verify the efficacy of multi-targeted herbal extracts.
Persistent Identifierhttp://hdl.handle.net/10722/343331

 

DC FieldValueLanguage
dc.contributor.authorLi, Mingyue-
dc.contributor.authorYue, Grace Gar Lee-
dc.contributor.authorLuo, Lianxiang-
dc.contributor.authorTsui, Stephen Kwok Wing-
dc.contributor.authorFung, Kwok Pui-
dc.contributor.authorNg, Simon Siu Man-
dc.contributor.authorLau, Clara Bik San-
dc.date.accessioned2024-05-10T09:07:15Z-
dc.date.available2024-05-10T09:07:15Z-
dc.date.issued2021-
dc.identifier.citationFrontiers in Oncology, 2021, v. 10, article no. 574827-
dc.identifier.urihttp://hdl.handle.net/10722/343331-
dc.description.abstractColorectal cancer is the third most frequently diagnosed cancer worldwide. Clinically, chemotherapeutic agents such as FOLFOX are the mainstay of colorectal cancer treatment. However, the side effects including toxicity of FOLFOX stimulated the enthusiasm for developing adjuvants, which exhibit better safety profile. Turmeric extract (TE), which has been previously shown to suppress the growth of human and murine colon xenografts, was further demonstrated here for its inhibitory effects on colon cancer patient-derived xenografts (PDX). PDX models were successfully established from tissues of colon cancer patients and the PDX preserved the heterogeneous architecture through passages. NOD/SCID mice bearing PDX were treated either with TE or FOLFOX and differential responses toward these treatments were observed. The growth of PDX, metastasis and tumor recurrence in PDX-bearing mice were suppressed after TE treatments with 60% anti-tumor response rate and 83.3% anti-metastasis rate. Mechanistic studies showed that TE reduced tumor cell proliferation, induced cell apoptosis, inhibited metastasis via modulating multiple targets, such as molecules involved in Wnt and Src pathways, EMT and EGFR-related pathways. Nevertheless, FOLFOX treatments inhibited the PDX growth with sharp decreases of mice body weight and only mild anti-metastasis activities were observed. Furthermore, in order to have a better understanding of the underlying mechanisms, network pharmacology was utilized to predict potential targets and mechanism. In conclusion, the present study demonstrated for the first time that oral TE treatment was effective to suppress the growth of colon PDX and the recurrence of colon tumors in mice. The findings obtained from this clinically relevant PDX model would certainly provide valuable information for the potential clinical use of TE in colorectal cancer patients. The application of PDX model was well illustrated here as a good platform to verify the efficacy of multi-targeted herbal extracts.-
dc.languageeng-
dc.relation.ispartofFrontiers in Oncology-
dc.subjectcolorectal cancer-
dc.subjectherbal medicines-
dc.subjectnetwork pharmacology-
dc.subjectpatient-derived xenografts-
dc.subjecttumor recurrence-
dc.subjectturmeric-
dc.titleTurmeric Is Therapeutic in Vivo on Patient-Derived Colorectal Cancer Xenografts: Inhibition of Growth, Metastasis, and Tumor Recurrence-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.3389/fonc.2020.574827-
dc.identifier.scopuseid_2-s2.0-85100456550-
dc.identifier.volume10-
dc.identifier.spagearticle no. 574827-
dc.identifier.epagearticle no. 574827-
dc.identifier.eissn2234-943X-

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