J Cancer 2022; 13(14):3554-3565. doi:10.7150/jca.77588 This issue Cite
Research Paper
1. Department of Plastic and Aesthetic (Burn) Surgery, the Second Xiangya Hospital of Central South University, Changsha, China.
2. Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China.
3. Department of General Surgery, the Third Xiangya Hospital of Central South University, Changsha, China.
4. Department of Pharmacy, the Second Xiangya Hospital of Central South University, Changsha, China.
5. Hunan Institute for Drug Control, Changsha, China.
6. Department of General Surgery, the Second Xiangya Hospital of Central South University, Changsha, China.
7. Department of Laboratory Medicine, the Second Xiangya Hospital of Central South University, Changsha, China.
8. Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Changsha, China.
9. Department of Intervention, Hunan Chest Hospital, Changsha, China.
Colorectal cancer (CRC) is one of the major killer diseases worldwide, and more effective therapeutic compounds for CRC treatment are urgently needed. Although bioactive natural products derived from endophytic fungi have been extensively employed as antibiotics and anticancer agents, little is known about the effect of Rhytidhysteron sp. BZM-9 (an endophytic fungus)-derived compounds on CRC. Herein, a natural molecule porric acid E was isolated from Rhytidhysteron sp. BZM-9. Alamar Blue cell viability assay, Western blotting, transmission electron microscopy, flow cytometry analysis, and fluorescence image examination were employed to evaluate the antitumor effects of porric acid E on CRC cell lines. To establish the xenograft tumor model, nude mice received subcutaneous implants consisting of CRC cells on their flanks. Then the mice were treated with porric acid E or vehicle to assess the tumor-killing effects. The results revealed that porric acid E exhibited cytotoxicity by inhibiting proliferation and promoting apoptosis in CRC cells in vitro. Additionally, compared with fluorouracil (5-FU), porric acid E exhibited a more potent inhibitory effect on CRC HT29 cells. Importantly, extensive autophagy induced by porric acid E was detected in CRC cells, whereas inhibition of autophagy could significantly ameliorate porric acid E-mediated cytotoxic effect on CRC cells. Moreover, porric acid E treatment could markedly suppress subcutaneous HT29 xenograft tumor growth in vivo. Bioinformatics prediction indicated that Beclin-1 might be the potential target of porric acid E. These findings might afford a useful and important method for the treatment of CRC through fungal endophyte-derived natural compounds.
Keywords: Colorectal cancer, Endophytic fungi, Natural compound, Apoptosis, Autophagy