Turmeric Is Therapeutic in Vivo on Patient-Derived Colorectal Cancer Xenografts: Inhibition of Growth, Metastasis, and Tumor Recurrence
Colorectal 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 bett...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.574827/full |
| _version_ | 1819051698378768384 |
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| author | Mingyue Li Mingyue Li Grace Gar-Lee Yue Lianxiang Luo Stephen Kwok-Wing Tsui Kwok-Pui Fung Kwok-Pui Fung Simon Siu-Man Ng Clara Bik-San Lau |
| author_facet | Mingyue Li Mingyue Li Grace Gar-Lee Yue Lianxiang Luo Stephen Kwok-Wing Tsui Kwok-Pui Fung Kwok-Pui Fung Simon Siu-Man Ng Clara Bik-San Lau |
| author_sort | Mingyue Li |
| collection | DOAJ |
| description | Colorectal 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. |
| first_indexed | 2024-12-21T12:08:04Z |
| format | Article |
| id | doaj.art-39ec02b0c19248dfb2981101f24ed387 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-21T12:08:04Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-39ec02b0c19248dfb2981101f24ed3872022-12-21T19:04:40ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-01-011010.3389/fonc.2020.574827574827Turmeric Is Therapeutic in Vivo on Patient-Derived Colorectal Cancer Xenografts: Inhibition of Growth, Metastasis, and Tumor RecurrenceMingyue Li0Mingyue Li1Grace Gar-Lee Yue2Lianxiang Luo3Stephen Kwok-Wing Tsui4Kwok-Pui Fung5Kwok-Pui Fung6Simon Siu-Man Ng7Clara Bik-San Lau8School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaInstitute of Chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, ChinaInstitute of Chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, ChinaThe Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, ChinaSchool of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaSchool of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaInstitute of Chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, ChinaDepartment of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, ChinaInstitute of Chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, ChinaColorectal 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.https://www.frontiersin.org/articles/10.3389/fonc.2020.574827/fullcolorectal cancerpatient-derived xenograftsturmerictumor recurrenceherbal medicinesnetwork pharmacology |
| spellingShingle | Mingyue Li Mingyue Li Grace Gar-Lee Yue Lianxiang Luo Stephen Kwok-Wing Tsui Kwok-Pui Fung Kwok-Pui Fung Simon Siu-Man Ng Clara Bik-San Lau Turmeric Is Therapeutic in Vivo on Patient-Derived Colorectal Cancer Xenografts: Inhibition of Growth, Metastasis, and Tumor Recurrence Frontiers in Oncology colorectal cancer patient-derived xenografts turmeric tumor recurrence herbal medicines network pharmacology |
| title | Turmeric Is Therapeutic in Vivo on Patient-Derived Colorectal Cancer Xenografts: Inhibition of Growth, Metastasis, and Tumor Recurrence |
| title_full | Turmeric Is Therapeutic in Vivo on Patient-Derived Colorectal Cancer Xenografts: Inhibition of Growth, Metastasis, and Tumor Recurrence |
| title_fullStr | Turmeric Is Therapeutic in Vivo on Patient-Derived Colorectal Cancer Xenografts: Inhibition of Growth, Metastasis, and Tumor Recurrence |
| title_full_unstemmed | Turmeric Is Therapeutic in Vivo on Patient-Derived Colorectal Cancer Xenografts: Inhibition of Growth, Metastasis, and Tumor Recurrence |
| title_short | Turmeric Is Therapeutic in Vivo on Patient-Derived Colorectal Cancer Xenografts: Inhibition of Growth, Metastasis, and Tumor Recurrence |
| title_sort | turmeric is therapeutic in vivo on patient derived colorectal cancer xenografts inhibition of growth metastasis and tumor recurrence |
| topic | colorectal cancer patient-derived xenografts turmeric tumor recurrence herbal medicines network pharmacology |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2020.574827/full |
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