Reactive oxygen species mediated apoptotic death of colon cancer cells: therapeutic potential of plant derived alkaloids

Abstract

Colorectal cancer (CRC) is one of the most deaths causing diseases worldwide. Several risk factors including hormones like insulin and insulin like growth factors (e.g., IGF-1) have been considered responsible for growth and progression of colon cancer. Though there is a huge advancement in the available screening as well as treatment techniques for CRC. There is no significant decrease in the mortality of cancer patients. Moreover, the current treatment approaches for CRC are associated with serious challenges like drug resistance and cancer re-growth. Given the severity of the disease, there is an urgent need for novel therapeutic agents with ideal characteristics. Several pieces of evidence suggested that natural products, specifically medicinal plants, and derived phytochemicals may serve as potential sources for novel drug discovery for various diseases including cancer. On the other hand, cancer cells like colon cancer require a high basal level of reactive oxygen species (ROS) to maintain its own cellular functions. However, excess production of intracellular ROS leads to cancer cell death via disturbing cellular redox homeostasis. Therefore, medicinal plants and derived phytocompounds that can enhance the intracellular ROS and induce apoptotic cell death in cancer cells via modulating various molecular targets including IGF-1 could be potential therapeutic agents. Alkaloids form a major class of such phytoconstituents that can play a key role in cancer prevention. Moreover, several preclinical and clinical studies have also evidenced that these compounds show potent anti-colon cancer effects and exhibit negligible toxicity towards the normal cells. Hence, the present evidence-based study aimed to provide an update on various alkaloids that have been reported to induce ROS-mediated apoptosis in colon cancer cells via targeting various cellular components including hormones and growth factors, which play a role in metastasis, angiogenesis, proliferation, and invasion. This study also provides an individual account on each such alkaloid that underwent clinical trials either alone or in combination with other clinical drugs. In addition, various classes of phytochemicals that induce ROS-mediated cell death in different kinds of cancers including colon cancer are discussed.

Intestinal Dysbiosis: Microbial Imbalance Impacts on Colorectal Cancer Initiation, Progression and Disease Mitigation

“…ROS cause CRC initiation via inflammation, DNA damage, epithelial-to-mesenchymal transition, apoptosis, and angiogenesis [37]. ROS also result in the initiation of mutations in various proteins involved with regulating the cell cycle (proto-oncogenes), including p53, Ras, and c-Myc, leading to oncogene activation [12]. Colibactin produced by enterotoxigenic E. coli with polyketide synthesis (pks) genomic islands alters cell cycle progression and induces DNA damage [21].…”

“…LPS is associated with cell adhesion, cell degradation, and cell invasion in CRC metastasis [43]. Studies have demonstrated that LPS-associated inflammation increases the activity of oncogenic genes and the cell proliferation of CRC in IBD animal models [12]. LPS also alters the integrity of the intestinal barrier by disrupting the tight junctions, leading to CRC tumorigenesis, tumor growth, leakage of microbial products into the bloodstream, systemic inflammation, and metabolic endotoxemia (ME) [43].…”

“…Pharmacodynamic and pharmacokinetic factors, including intestinal pH, drug solubility, non-selective targeting, and adverse drug reactions, impact chemotherapy treatment [7]. Chemotherapeutic drug candidates for CRC, including 5-fluorouracil, oxaliplatin, capecitabine, and irinotecan, are also cytotoxic to normal cells [12]. The classical drug fluorouracil has high resistance, with a response rate of less than 10% in CRC patients [13].…”

Integrating network pharmacology with molecular docking to rationalize the ethnomedicinal use of Alchornea laxiflora (Benth.) Pax & K. Hoffm. for efficient treatment of depression

“…However, a few medicinal plants have been evaluated extensively for their antidepressant mechanism of action (Maina et al, 2020). An array of studies has revealed that medicinal plants may hold the key to discovering lead chemicals for innovative therapeutics against several neurological disorders (Wal et al, 2022;Wal et al, 2023 A.;Wal et al, 2023 P.;Alrouji et al, 2023;Nelson et al, 2023). Hence, research in this area could help develop effective management of psychiatric disorders in Africa.…”

Isorhamnetin Influences the Viability, Superoxide Production and Interleukin-8 Biosynthesis of Human Colorectal Adenocarcinoma HT-29 Cells In Vitro

“…The increased mitochondrial dysfunction makes the cancer cells more vulnerable to oxidative stress than normal cells. Therefore, a minor rise in ROS levels caused by external stimuli can cause cancer cell death through a variety of death pathways [ 30 ]. This mechanism has led to the development of pro-oxidant therapy, which uses agents to cause oxidation-induced cell death, as a potent method of cancer treatment [ 31 ].…”