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Active Compound of Pharbitis Semen (Pharbitis nil Seeds) Suppressed KRAS-Driven Colorectal Cancer and Restored Muscle
Jisu Song1,2, Heejung Seo1,3, Mi-Ryung Kim1
1Department of Food Biotechnology, School of Medical and Life Science, Silla University, Busan 46958, Korea.
Abstract:
Kirsten rat sarcoma viral oncogene homolog (KRAS)-driven colorectal cancer (CRC) is notorious to target with drugs and has shown ineffective treatment response. The seeds of Pharbitis nil, also known as morning glory, have been used as traditional medicine in East Asia. We focused on whether Pharbitis nil seeds have a suppressive effect on mutated KRAS-driven CRC as well as reserving muscle cell functions during CRC progression. Seeds of Pharbitis nil (Pharbitis semen) were separated by chromatography and the active compound of Pharbitis semen (PN) was purified by HPLC. The compound PN efficiently suppressed the proliferation of mutated KRAS-driven CRC cells and their clonogenic potentials in a concentration-dependent manner. It also induced apoptosis of SW480 human colon cancer cells and cell cycle arrest at the G2/M phase. The CRC related pathways, including RAS/ERK and AKT/mTOR, were assessed and PN reduced the phosphorylation of AKT and mTOR. Furthermore, PN preserved muscle cell proliferation and myotube formation in cancer conditioned media. In summary, PN significantly suppressed mutated KRAS-driven cell growth and reserved muscle cell function. Based on the current study, PN could be considered as a promising starting point for the development of a nature-derived drug against KRAS-mutated CRC progression.
Insights
Pharbitis nil seed extract (PN) effectively inhibits KRAS-mutated colorectal cancer (CRC) cell growth and preserves muscle cell function. PN shows potential as a nature-derived drug for treating KRAS-mutated CRC.
Area of Science:
- Pharmacology and Natural Products Chemistry
- Oncology and Cancer Biology
- Gastroenterology
Background:
- KRAS-driven colorectal cancer (CRC) presents significant therapeutic challenges due to drug resistance.
- Traditional East Asian medicine utilizes Pharbitis nil seeds (morning glory) for therapeutic purposes.
- The potential of Pharbitis nil in managing KRAS-mutated CRC and associated muscle wasting remains unexplored.
Purpose of the Study:
- To investigate the suppressive effects of Pharbitis nil seeds on KRAS-mutated CRC.
- To determine if Pharbitis nil can preserve muscle cell functions during CRC progression.
- To identify and characterize the active compound from Pharbitis nil seeds.
Main Methods:
- Purification of the active compound (PN) from Pharbitis nil seeds using chromatography and HPLC.
- Assessment of PN's effect on KRAS-mutated CRC cell proliferation, clonogenic potential, apoptosis, and cell cycle.
- Analysis of CRC-related signaling pathways (RAS/ERK, AKT/mTOR) and evaluation of PN's impact on muscle cell proliferation and myotube formation in conditioned media.
Main Results:
- PN significantly suppressed KRAS-mutated CRC cell proliferation and clonogenic potential in a dose-dependent manner.
- PN induced apoptosis and G2/M cell cycle arrest in SW480 human colon cancer cells.
- PN reduced AKT and mTOR phosphorylation, and preserved muscle cell proliferation and myotube formation in cancer-conditioned media.
Conclusions:
- Pharbitis nil seed extract (PN) demonstrates potent anti-cancer activity against KRAS-mutated CRC.
- PN effectively preserves muscle cell function, mitigating cancer-associated muscle wasting.
- PN represents a promising natural-derived compound for developing novel therapeutic strategies against KRAS-mutated CRC.
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