Preparation and anti-colon cancer effect of a novel curcumin analogue (CA8): in vivo and in vitro evaluation
Chemotherapy remains the first choice of treatment for colon cancer despite the inevitable adverse effects. Curcumin (CU) possesses antitumor activity but has poor aqueous solubility, low bioavailability, and weak activity. To address this, nine novel monocarbonyl CU analogues were designed, synthes...
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Frontiers Media S.A.
2024-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1464626/full |
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| author | Jie Wen Jie Wen Jie Wen Lingmao Zhao Zhuohan Li Chao Pi Chao Pi Xianhu Feng Xianhu Feng Peng Shi Peng Shi Hongru Yang Ligang Chen Xiaodong Wang Furong Liu Yumeng Wei Yumeng Wei Ling Zhao Ling Zhao |
| author_facet | Jie Wen Jie Wen Jie Wen Lingmao Zhao Zhuohan Li Chao Pi Chao Pi Xianhu Feng Xianhu Feng Peng Shi Peng Shi Hongru Yang Ligang Chen Xiaodong Wang Furong Liu Yumeng Wei Yumeng Wei Ling Zhao Ling Zhao |
| author_sort | Jie Wen |
| collection | DOAJ |
| description | Chemotherapy remains the first choice of treatment for colon cancer despite the inevitable adverse effects. Curcumin (CU) possesses antitumor activity but has poor aqueous solubility, low bioavailability, and weak activity. To address this, nine novel monocarbonyl CU analogues were designed, synthesized, and evaluated in the present study. Among them, CA8 exhibited the highest water solubility, which was approximately 2.37 × 106 times that of CU. In addition, compared with CU, its cytotoxicity on Caco-2 cells (19.2 times/48 h) was stronger. Of note, CA8 arrestedthe cell cycle of Caco-2 cells at the G2/M phase and induced apoptosis. Meanwhile, acute toxicity experiments indicated that KM mice tolerated CA8 for up to 300 mg/kg CA8 (oral administration) and 50 mg/kg CA8 (intraperitoneal injection). The oral administration of CA8 to Sprague Dawley rats exhibited higher AUC (0-t) (6.23-fold) and longer MRT (0-t) (3.35-fold) than that of CU. CA8 also inhibited the proliferation and angiogenesis of tumor cells more than CU and tegafur. Finally, CA8 may exert anti-tumor effects through the activation of JNK pathway and inhibition of AKT pathway. These results suggest that CA8 is a safe and highly effective new drug for colon cancer treatment. |
| format | Article |
| id | doaj-art-935184028d3342429507fb42352eadde |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-935184028d3342429507fb42352eadde2024-11-12T09:41:29ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-11-011510.3389/fphar.2024.14646261464626Preparation and anti-colon cancer effect of a novel curcumin analogue (CA8): in vivo and in vitro evaluationJie Wen0Jie Wen1Jie Wen2Lingmao Zhao3Zhuohan Li4Chao Pi5Chao Pi6Xianhu Feng7Xianhu Feng8Peng Shi9Peng Shi10Hongru Yang11Ligang Chen12Xiaodong Wang13Furong Liu14Yumeng Wei15Yumeng Wei16Ling Zhao17Ling Zhao18Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, ChinaLuzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, ChinaCentral Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, ChinaLuzhou Longmatan District People’s Hospital, Luzhou Third People’s Hospital, Luzhou, Sichuan, ChinaKey Laboratory of Medical Electrophysiology, Ministry of Education, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, ChinaKey Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, ChinaCentral Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, ChinaKey Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, ChinaNanchong Key Laboratory of Individualized Drug Therapy, Department of Pharmacy, Nanchong Central Hospital, Nanchong, Sichuan, ChinaLuzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, ChinaCentral Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Hepatobiliary Diseases, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China0Department of Oncology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, ChinaKey Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, ChinaCentral Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, ChinaLuzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, ChinaCentral Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, ChinaChemotherapy remains the first choice of treatment for colon cancer despite the inevitable adverse effects. Curcumin (CU) possesses antitumor activity but has poor aqueous solubility, low bioavailability, and weak activity. To address this, nine novel monocarbonyl CU analogues were designed, synthesized, and evaluated in the present study. Among them, CA8 exhibited the highest water solubility, which was approximately 2.37 × 106 times that of CU. In addition, compared with CU, its cytotoxicity on Caco-2 cells (19.2 times/48 h) was stronger. Of note, CA8 arrestedthe cell cycle of Caco-2 cells at the G2/M phase and induced apoptosis. Meanwhile, acute toxicity experiments indicated that KM mice tolerated CA8 for up to 300 mg/kg CA8 (oral administration) and 50 mg/kg CA8 (intraperitoneal injection). The oral administration of CA8 to Sprague Dawley rats exhibited higher AUC (0-t) (6.23-fold) and longer MRT (0-t) (3.35-fold) than that of CU. CA8 also inhibited the proliferation and angiogenesis of tumor cells more than CU and tegafur. Finally, CA8 may exert anti-tumor effects through the activation of JNK pathway and inhibition of AKT pathway. These results suggest that CA8 is a safe and highly effective new drug for colon cancer treatment.https://www.frontiersin.org/articles/10.3389/fphar.2024.1464626/fullmonocarbonyl CU analoguescolon cancerAKTJNKapoptosis |
| spellingShingle | Jie Wen Jie Wen Jie Wen Lingmao Zhao Zhuohan Li Chao Pi Chao Pi Xianhu Feng Xianhu Feng Peng Shi Peng Shi Hongru Yang Ligang Chen Xiaodong Wang Furong Liu Yumeng Wei Yumeng Wei Ling Zhao Ling Zhao Preparation and anti-colon cancer effect of a novel curcumin analogue (CA8): in vivo and in vitro evaluation Frontiers in Pharmacology monocarbonyl CU analogues colon cancer AKT JNK apoptosis |
| title | Preparation and anti-colon cancer effect of a novel curcumin analogue (CA8): in vivo and in vitro evaluation |
| title_full | Preparation and anti-colon cancer effect of a novel curcumin analogue (CA8): in vivo and in vitro evaluation |
| title_fullStr | Preparation and anti-colon cancer effect of a novel curcumin analogue (CA8): in vivo and in vitro evaluation |
| title_full_unstemmed | Preparation and anti-colon cancer effect of a novel curcumin analogue (CA8): in vivo and in vitro evaluation |
| title_short | Preparation and anti-colon cancer effect of a novel curcumin analogue (CA8): in vivo and in vitro evaluation |
| title_sort | preparation and anti colon cancer effect of a novel curcumin analogue ca8 in vivo and in vitro evaluation |
| topic | monocarbonyl CU analogues colon cancer AKT JNK apoptosis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1464626/full |
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