Characteristics of programmed cell death are generally regarded as defined by cell outgrowth or cellular aging and distinct morphological characteristics featuring nuclear condensation and formation of apoptotic bodies. Apoptosis is considered to have a function at cellular level and is essential to long-lived cell differentiation undergoing senescence and apoptosis. Inappropriate apoptosis is a factor that results in serious conditions, causing multiple disease progression as well as cancer. The ability to modulate the life or death of a cancer cell is recognized for its immense therapeutic potential. Therefore, the research findings that are focused on the elucidation of a newly synthesized drug or drug derived from a natural plant to stop the cell cycle mechanism and signaling pathways that control cell cycle arrest and apoptosis are considered necessary. The field research of apoptosis is moving forward at a rapid rate. The goal of this paper is to investigate a natural active constituent, which is simply identified as “a drug for near future co-chemotherapy”, as well as to explore the ability to activate the apoptotic pathway. Our results demonstrated that cyclopamine provides an excellent anti-tumor activity and changing of the morphology of cancerous cells in the early and late phases of apoptosis, indicating that cyclopamine has the potential to chemosensitize SW-620 cancer cells to 5-FU based chemotherapy, which may be useful for the treatment of colorectal cancer and the fight to overcome drug resistance in advanced colorectal cancer.
Centella Asiatica has been traditionally used as herbal medicine to treat various disorders, such as ulcers and psoriatic disease. ECa233 is an herbal extract of Centella Asiatica containing madecassoside (46.3 %) and asiaticoside (41.6 %) that shows a highly acceptable safety profile appropriate for drug development and use as an herbal drug for humans. 5-fluorouracil (5-FU) is a chemotherapeutic agent generally known as the first-line chemotherapy for colorectal cancer. Representative combined chemotherapy with 5-FU, namely the FOLFOX regimen (5-FU, leucovorin, oxaliplatin), has been widely used in hospitals and is typically selected as a chemotherapeutic regimen in prescriptions. However, the unresolved problems appearing in clinical situations are the refusal to accept the chemotherapy leading to drug resistance and the severe side effects after being administered intravenously to the entire body. Therefore, the discovery of a novel pure standard agent to enhance the efficacy of 5-FU and overcome this drug resistance still needs to be explored. To assess the pharmacological activity and safety profile of ECa233 is a major goal in cancer drug discovery. ECa233 was evaluated for its anti-cancer, anti-migration, anti-invasive activities and was explored regarding the safety data on normal cells. The results demonstrated that ECa233 effectively inhibited the cell viability, colony forming, and truly inactivated cell migration/invasion through repressive the MMP-9 invasive factor. Pharmacological interaction with 5-FU was synergism in cancer cells and highly safe to normal cell growth. The results suggest that ECa233 could be used as a combinative drug therapy with standard chemotherapy treatment and other medicinal drugs such as a targeted therapy to treat colorectal cancer patients.
Drug resistance is a major inconvenience which lowers the traditional chemotherapeutic efficacy and is a highly undesirable therapeutic problem which poses particular challenges in the case of colorectal cancer. Fucoxanthin is a natural orange-carotenoid, predominantly found in edible brown algae and justifiably considered as a nutritional ingredient with the capacity to powerfully enhance concurrent drug chemotherapy. It has been well-documented that fucoxanthin has good potential for anti-cancer activity while offering a remarkable range of biological activities. Accordingly, it has gained prominence in the research field as interest grows in the molecular mechanism which is associated with cancer therapy. This study was undertaken to assess the anti-cancer activity and to explore the molecular mechanism of fucoxanthin on the inhibition of cell proliferation, cell adhesion, and cell invasion, in addition to determining the synergistic effect of drug-drug combinative treatment in colorectal cancer cells. SW-620 cells were cultivated with fucoxanthin for 24, 48, 72, and 96 hours with co-treatment by 5-FU to evaluate the synergistic potential. The cell viability of cancerous cells was determined by MTT colorimetric assay. The inhibitory effects of cell invasion and adhesion were measured in the presence of fucoxanthin with 5-FU in various concentrations to determine MMP-9 gene and protein expression after treatment of the cells by RT-PCR and ELISA assay. The results illustrated that fucoxanthin profoundly inhibited cell proliferation of SW-620 cells, accompanied by arrested growth and diminished invasive ability, which was mediated at least in part by the down-regulation of MMP-9, mRNA, and protein expression. In particular, fucoxanthin strongly attenuated the anti-proliferative effect of established 5-FU by modulating the habitual hallmark of cancerous cells. These results illustrate the capacity of fucoxanthin to eradicate cancer cells and indicate the possibility that fucoxanthin could serve as a promising natural marine product derived from seaweed. The critical data in our studies will serve as the preliminary results for further studies of marine drugs in both experimental models and well-controlled clinical trials.
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