Plant-Derived Alkaloids as a Potential Source of Treatment for Colorectal Cancer over the Past Five Years: A Comprehensive Review

Abstract

The gastrointestinal cancer known as colorectal cancer (CRC) is caused by a variety of genetic and epigenetic alterations in the intestinal epithelium of the colon and rectum. It is becoming more common every year. In view of this significant progress, it is urgent and imperative for researchers to work more in this direction in order to improve this health situation that is a major concern for society. Certain phenomena, such as the development of resistance by certain cells as well as the failure of certain therapies, play a part in the significantly changed situation. However, plants have always been used for their therapeutic virtues due to the large number of compounds they contain. Among them, alkaloids (more than 20,000 alkaloids have been isolated from plants, of which about 600 are known to be bioactive), which are one of the most diverse and extensively investigated classes of compounds among natural products, can be consider as a promising approach with regard to their numerous biological activities in general and, in particular their activities against colorectal cancer. This work aims to undertake deeper research on the examination of alkaloids that can be used as lead compounds in the treatment of colorectal cancer. The databases used during the literature searches were Web of Science, PubMed/Medline, and Scopus. This methodology allowed us to obtain 11 studies and 24 alkaloids (axidimins A–D, tabersonine, 19R-hydroxytabersonine, 11-hydroxytabersonine, 11-methoxytabersonine, vandrikidine, fusiformine A, 3-oxotabersonine, 3-oxo-11-methoxytabersonine, melodinine W2, venalstonidine, scandine, (–)-larutienine A, solasonin, berbamine dihydrochloride, nitidine chloride, GB7 acetate, berberine, boldine, Worenine, and chaetocochin J). Axidimin C and axidimin D showed significant cytotoxic effects on CRC (HCT116 cells) with IC50 values of 5.3 and 3.9 μM, respectively, and they were more active than 5-fluorouracil and etoposide (IC50 = 6.4 and 10.6 μM, respectively) taken as references. These two compounds induced G2/M phase arrest in HCT116 cells by downregulating cyclin B1 and cdc2 expression. Subsequently, promoting apoptosis via modulation of Bax and Bcl-2 levels, they enhanced p38 MAPK expression, leading to G2/M cell cycle arrest and apoptosis in HCT116 cells. Chaetocochin J possess significant activity against three different CRC cell lines [RKO (0.5 μM < IC50 = 0.56 μM < 1.0 μM), HCT116 (0.5 μM < IC50 = 0.61 μM < 1.0 μM) and SW480 (0.5 μM < IC50 = 0.65 μM < 1.0 μM)]. The 21 remaining compounds have a moderate anti-colorectal cancer activity. Thus, we believe that axidimin C, axidimin D and chaetocochin J could be promising compounds to fight colorectal cancer cell carcinoma. Nevertheless, future analysis should be performed on the study of the toxicologies of axidimin C and axidimin D.