Active Compound of Pharbitis Semen (Pharbitis nil Seeds) Suppressed KRAS-Driven Colorectal Cancer and Restored Muscle Cell Function during Cancer Progression

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.

Emerging Role of Plant-Based Dietary Components in Post-Translational Modifications Associated with Colorectal Cancer

“…In the case of AKT, serine phosphorylation (S473) was upregulated in CRC. Some studies revealed that harmine [ 151 ], ophiopogonin D [ 154 ], and luteolin [ 157 ] were able to downregulate this specific serine phosphorylation, while others such as coumarins [ 119 ], resveratrol [ 125 ], quercetin [ 140 ], secoisolariciresinol diglucoside [ 145 ], lycopene [ 158 ], and some plant extracts decrease protein phosphorylation [ 168 , 169 ]. Similarly, in PI3K and BCL2 proteins, quercetin, secoisolariciresinol diglucoside, and iodine-biofortified lettuce extract downregulated their phosphorylation, respectively [ 140 , 145 , 164 ].…”

Potential Role of Traditional Chinese Medicines by Wnt/β-Catenin Pathway Compared With Targeted Small Molecules in Colorectal Cancer Therapy

“…Up to 40% of KRAS mutations occur in patients with CRC ( Arrington et al, 2012 ). The discovery of small-molecule RAS inhibitors or a siRNA targeting RAS displayed anti-proliferative activity on xenografts of human CRC cell line SW480 ( Song et al, 2020 ). The mutations of KRAS result in the hyper-activation of RAS-extracellular signal-regulated kinase (ERK) pathway involving transformation of cells and tumorigenesis.…”

Editorial to the Special Issue “Biological and Pharmacological Activity of Plant Natural Compounds”

“…Seeds of Pharbitis nil (L.) Choisy, a traditional plant used in East Asia to treat inflammation and cancer, were used in cell models of colorectal cancer to evaluate the antiproliferative effects of the purified extract [ 6 ]. Cell cycle modulation and apoptosis induction were observed, with changes in the RAS/ERK and AKT/mTOR pathways.…”